European .hmrmd qf Suwical Oncolofly 1995:21
: 697-703
British Association of Surgical Oncology 51st Scientific Meeting, held at The Royal College of Surgeons of England, 35-43 Lincoln's Inn Fields, London on 23 November 1995 Abstracts of members' papers
T b e training and expectations of breast surgeons
S. Woodhams and R. Rainsbury Breast L'nit. Royal Ilampshire ('olmty Hmpital. II'im'he.ster S022 5DG, L'K Training programmes for breast snrgeons (BS) are holly debated. Questionnaires were seat to ~t)4 consulhlnt surgeons (CS) and 166 higher surgical trainees (HST) in Southern England to identify those perlbrming BS and establish (a) other interests and work load (b) training and experience (cJ future expectations. One hundred and twenty-eight ot"322 respondents expressed an interest in BS (43% CS. 34% HST). Ibrming the basis of this study. One hundred and seven 184%) identilied gastrointeslinid, colorectal or endocrine surgery as a second special interest. (in decreasing order of preference). Forty seven per cent see < I(I ne~~. patients per v.'eck (35 CS, 25 FIST) and 30% see > 211 per week 133 CS. 5 HST). Few BS wish to reduce other commitments [24% CS, 24% FIST) or delegate to colleagues (26'!,,, CS. 18% HST), but most support diagnostic nurse practitioners (66% CS. 53°o HST) and 'onestop" clinics (7t)'% CS. 90% HST). Standard operations are generally well taught with 68% HST trained by specialists. Only 21'% CS perform breast reconstruction (BR). as 65% are untrained. Sixty-four per cent favour delayed BR but rarely by a BS 121%1. By contrast. 42% FIST perlbrm BR. lavouring immediate BR 160'%1 by a BS 158'!,1. Forty-one per cent of CS and 85'% of HST would like further training m BR. The popularity of BS is not incrcasing and surgeons are keen to maintain other interests. This situation is unlikely to improve until or unless training expectations are addressed, particularly in the [ield of reconstruction.
Prevalent screen results from a family history breast cancer clinic J. Kollias, D. M. Sihberlng, P. A. M. Holland, A. R. M, Wilson, A. J. Evans, C. W. Elston, I. O. Ellis, J. F. R. Rohertson and R. W. Blarney CiO' Ih~,spital. Nottingham. L"K Family history is an established risk factor for breast cancer. An increasing number of women are being referred to specialist breast clinics Ibr advice regarding screening. The Nottingham City Hospital Family History Clinic was established in 1988. Asymptomatic patients with a history of at least one lirst degree relative or two second degree relatives with breast cancer are eligible to enter. Resuhs from the prevalent round arc now available Ibr 1674 patients who have entered the Family History Clinic. Thirteen patients (median age 42 years) were found to have cancer at their lirst visit (8.1 per 1000 women screened). Six cancers were detected by mammography alone 13 in-situ. 3 invasive) and 7 by clinical examination and mammography (all invasive). According to the Nottingham Prognostic Index. 3 invasive cancers were of good prognosis, 3 were of medium prognosis and 4 were of poor prognosis. Coochtsions [I) The prevalent cancer detection rate ill wonlen attending this family history clinic Imedian age 42 years)is comparable to that in women over 5(J years attending the N HS Breast Screening Programme. (2) Ahuost halfof the cancers detected in the prevalent screening round were in-situ or good prognosis invasive cancers.
Parotid carcinomas. Prognostic factors and optimum treatment i A. Renehan*, M. MeGurk'l"and E. N. Gleave* * Universit.v Departownt of Surgery. South Mmwhester Unirersity Ho.ff;ital & Christie Hospital. Mmwhester; JrDepartment of Oral & Maxillo/iwial Surt, ery. UMDS. Guy's Dental Seh,ol. Lomhm. UK A retrospective study of 117 new parotid carcinomas treated at the Christie Hospital. Manchester. between 1947 and 1992, is reported. All cases were treated delinitively by either surgery alone (n = 35). surgery plus adjuvant radiotherapy In = 621. or radiotherapy alone (n = 20). The 5-. 10- and 15[)748 7983,95060697+(17 512.00/0
year cause specilic survival rates were 70%. 60% and 57% respectively. Univariate analysis for prognostic factors showed thai, in order of priority, turnout stage, nodal metastases, facial nerve pals'.', fixity, histological type and age, all influenced survival. After multivariate analysis, tumour size was the most signilicant factor (P < 0.0001 ). In the advanced tumour group [T3 T4). patients treated with combined therapy had a 10-year relapse-free survival rate of 45% compared to 13% for those treated by surgery alone (P = 0.005). The same rates in the early turnout group (TI ,T2} were 78% and 75%. respectively. The main indications for the use of adjuvant radiotherapy in smaller turnouts were positive margins and high grade. The conclusion is that surgery combined with radiotherapy prorides a significant survival advantage in the treatment of advanced parotid maligmmcies.
Clinical significance of p53 expression in oesophageal cancer Y. Mohsen, R. Conrad and M. C. Winslet L"niversit.v DtTartment of Surgery, Royal Free Hospital & School of Medichw. Lomhm. L'K The tumour suppressor gene p53 is believed to play an important role in the progression of human malignant turnouts Ihrough mutation or overexpression To examine the clinical signilicance of the expression and accumulation of p53 in oesophageal cancer. 100 formalin fixed paraflin-embedded. specimens of oesophageal cancer were analysed immunohistoehemically using a monoclonal antibody (DO-7. DA KO) and microwave oven heating method. Cell proliferation index for all tumours was calculated from immunostaining with the M I B- I monoclonal antibody and correlated with clinical parameters as well as p53 status Of the 100 tumours. 39% were adenocarcinoma, 54°/. squamous cell carcinoma, 3",'0 oat cell carcinoma and 4"/o undifferentiated. Twenty-nine per cent of all the tumours were p53 negative. 71% p53 positive with a mean posilivity percentage o1"59.4 (_+25.4). The age. sex, site. turnout differentiation, lymph node status, distal metastases, treatment and survival was correlated to p53 status and cell proliferation index. Correlations were found between p53 status, proliferation index (P < 0.001 ), treatment, stage and survival (P < 0.[1051. Overall the cumulative survival rate of patients with p53 expression was lower than that of the patients without expression (P < 0.05). The prognostic value of p53 appears to be highly signilicant in surgically resected cases of squamous cell carcinoma {P < 11.021.
Levels of soluble cell adhesion molecules are of limited use in the assessment of patients with gastric cancer D. Karat, L. Brolherick, D. M. O'Hanlon, B. K. Shenton S. A. Raimes and S. M. Griffin Dept. o/Surgery. Medical School. Unh'ersi O" of Newcasth' upon Tvne. UK Cell adhesion molecules are expressed by many cancers and are known to play an important role in the growth, differentiation and dissemination of tumour cells. Many of these adhesion molecules are detectable in a soluble form in serum. This prospective study wits established to measure the serum levels of Ibur different cell adhesion molecules in patients with primary gastric cancer (GC) and to investigate their role in the assessment of patients with this disease. The molecules studied were ICAM-I (IC), VCAM [VC). ESelectin (ES) and E-Cadherin (EC). Pre-operative serum samples were collected from 50 patients with GC as well as 16 age/sex matched heahhy controls and immunoassays were performed with a commercially available ELISA kit. Serum levels were expressed as ng/ml. Statistical analysis was performed using Mann-Whimey U and Spearman Correlation tests. There were signilicant positive correlations between levels of IC. VC and ES in patients with GC (P < 0.001). The mean(SEM] serum ES was sig~" 1995 W.B. Saunders Comoanv Limited
698
Ahstracts
nificantly lower in GC patients than controls [37.65(4.55) vs 58.64(5.03): P < 0.01]. but there were no significant differences for the other adhesion molecules. IC was significantly higher in patients with poorly differentiated tumours compared to well differentiated tumours [476(42.2) vs 345(32.7): P < 0.05]. and ES was significantly lower in serosa positive patients compared to serosa negative patients [38.76(6.15) vs 47.36(4.9)]. There were no significant differences for EC and VC between these groups. None of the adhesion molecules studied showed any significant differences Ibr nodal status or T-stage of the tumour. In summary this study demonstrates that levels of soluble adhesion molecules, in contrast to their role in other cancers, are of little use in the assessment of patients with gastric cancer.
Differential expression of a novel variant of F G F R - I in the h u m a n breast C. Yiangou*, Caroline Johnston't, H. D. Sinnett* and R. C. Coombes+ Departments r~/"*Surger.v and "~Medical Ontology. Charing Cross Hospital. Lon&m. UK The family of FGFs consists of nine polypeptides which are involved in cellular growth, differentiation, angiogenesis and carcinogenesis. Their cellular response is mediated througb binding to cell surface receptors (FGFRs) with tyrosine kinase activity. We have investigated the expression of FGFR-I proteiu, by Western blotting and immunohistochemistry, in a panel of 7 normal and malignant mammary c~ll lines, separated epithelial and myoepithelial cells, breast fibroblasts and 22 breast tissues. Three variant fonlls of FGFR-I were detected and their relative distribution differed in normal and malignant breast cells. In the 4 malignant cell lines only the/1 form of FGFR-I was detected, whereas in the 3 nonmalignant cells lines and the normal epithelial cells this co-existed with a novel, smaller isoform, truncated at its C-terminus. Myoepithelial cells and fibroblasts, on the other hand, expressed only the smaller isoform. Similar results ,.,,,ere obtained for the breast tissues, with the normal and benign ones expressing high levels of the new variant and breast cancers expressing the ~t and [J forms, with the latter being the predominant form in 80% of them. In this study, we have described a novel, truncated variant of FGFR-I which is present only in normal breast cells. It most probably lacks tyrosine kinase activity and acts as a dominant negative receptor and, therefore, its absence in breast cancer may have profound consequences on cellular growth ,and differentiation. F G F = fibroblast growth factor F G F R = fibroblast growth factor receptor C-terminus = carboxy-terminus
Staging breast cancer with magnetic resonance imaging (MRI) H. Mumtaz, T. Davidson, M. HalI-Craggs*, M. Payley* and I. Taylor Departments o/Surgery attd Imaging*. UCL Medical School. London. UK While triple assessment achieves high diagnostic accuracy in breast cancer, it has limitations in defining the local extent of disease and axillary node metastases. We have evaluated M RI in staging breast cancer compared to clinical and mammographic examinations. Sixty women with primary breast cancer were prospectively evaluated by MRI and mammography. MRI was performed using a dedicated double breast coil on a I Tesla scanner before and after enhancement with gadolinium. MRI and mammography were concordant in 60% (36 patients) with 31 unifoeal and 5 multifocal cancers. O f the 24 patients (40%) with discordant results, mammography was normal (n = 13J, falsely negative for multifocal cancer (n = 9) and falsely positive Ibr multifocal cancer (n = 2). MRI identified all but 3 invasive cancers teach 4 mm in size) which were obscured by areas of diffuse patchy enhancement. In 3 patients, breast MRI showed an additional enhancing focus not confirmed histologically. Tumour size and stage measured by MRI had a better correlation with histopathologic analysis than did mammography (r = 0.86 v r = 0.45). In addition, M RI had higher sensitivity than mammography for detecting extensive intraduct component (70% v 40'/.). Mammography was not useful in diagnosing axillary node metastases. M RI was able to assess the axillae in 45 of the 60 patients with a sensitivity and specificity for axillary node metastases of 90"/o and 9 5 0 respectively. In conclusion. MRI is of value in the preoperative Iocoregional staging of primary breast cancer.
Does emotional suppression and depressed mood predict immunosuppression in patients with lung disease? L. L. Millar*, K. Peterson*, L. G. Walker*, P. W. Whiting'f, D. B. Gough*, J. A. R. Friend:[:and O. Eremin* *Departments t~" Surgery trod Behaeioural Oncology ~fClinical Biochemistry and ~ Thoracic Medichw. Unhrersit.v of Aberdeen. UK Emotional suppression and tendency to depression are central features of the Type C (cancer-prone) personality. Ahhough there is evidence that the Type
C personality increases the risk of developing cancers, and may also impair survival, the underlying mechanisms are unclear. A study was undertaken. therefore, to investigate the psycho-immunological relationsbips in patients undergoing the stress of inpatient investigations because of suspected hmg cancer. Forty patients were recruited: 23 were Ibund to have lung cancer and 17 benign disease. The groups were comparable for agc. smoking history and gender ratio. Psychological characteristics were assessed using the Courtauld Emotional Control Scale (CECS) (measures suppression of anger, anxiety and unhappiness) and the Hospital Anxiety and Depression Scale. Immunological parameters studied were in vitro. Mitogen responses (Concanevalin A [Con A] and Pokeweed [PWM], Natural Killer (NK) and Lymphokine Activated killer (LAK) cell activity of blood lymphocytes, serum cytokincs [intcrlcukinI (IL-I). IL-2 and IL-6] and immunoglnbulins lgG. IgM and IgA. using standard techniques. Psychometric and immunological parameters were correlated for each group separately using Kendall's tau. Alpha was set at 0.05 [2-tailed). For patients with benign disease, depression scores were negatively correlated with responses to PWM 10.5 ilg/ml (-(I.53), 2 itg~ml ( - 0 . 4 7 ) and 8 ttg ml] and Con A [7.8 i~gml (-(I.41). 31.2 i~gml ( - 0 . 4 4 ) and 125 p g m l 1(I.49)I. Also. CECS total scores were negatively correlated with PWM [2 pg:ml I - 0 . 3 5 ] and 8 #g/nal (-0.37)1 and Con A [7.8 ilgml ( - 0 . 4 2 ) , and 125 m itgiml ( -0.43)]. CECS anger correlated negatively with serum levels of IL-2 (-0.411 and positively with serum levels of IL-I (0.47). CECS anxiety correlated negatively with serum levels of IL-2 ( -0.401 and CECS unhappiness correlated positively with IL-I (0.40). For the cancer patients. CECS anger was negatively correlated with NK activity ([I.32). CECS anxiety was negatively correlated with serum levels of IL-6 (-{).38) and CECS unhappiness was negatively correlated with IgG (-0.33). Depression scores were positively correlated with IgA (0.32) and IgM ((I.33). Without exception, the correlations in the benign group are all in the direction prediction and provide clear evidence o f psychoimmuoological mechanisms. Hov.,ever. the different pattern in the cancer patients suggests that turnout burden may have a deranging elt~:ct.
Combination of intraluminal and external beam radiotherapy is effective treatment inpatients presenting with o e s n p b a g e a l carcinoma U. Matthiensen, J. Halford, D. M. O'Hanlon, M. Harkin, D. Karat, P. Da~'es*, S. M. GriFfinand M. B. Clague Depts qf Surgery and * Rudintherap.v, Newcasth, General Hospital. Newcasth, upotl Tl'ne. UK Ocsophageal carcinoma is uncommon, accounting Ibr 2% of all cancer deaths. The majority of patients arc elderly, have advanced disease and are unfit Ibr surgery. Radiotherapy offers effective palliation in many of these patients and can be delivered by external beam (EBR) or intralumimdly. Conventiomd intraluminal selection therapy involves prolonged wbich may be associated with procedure related complications. Microselcctron has a major adwmlagc in that the procedure is completed in a shorter period of time. Since 1993. 85 patients have undergone microseiectron in this unit. Data was collected prospectively on all patients. The mean(SEM) age of patients was 72.5(0.9) years and 35 were female. All patients had EBR and a median dose of 30 cGy was delivered. Ten cGy was delivered intraluminally over a mean(SEM) of 9.510.5) minutes using a remote afterloading technique. The median survival Ibllowing microselectron was 22 weeks 195% conlidence intervals 18.1-25.9 weeks). Survival ',,,'as dependent on: the length of tumour-- ~< 3 cm 47II2.8) weeks Vs > 4 cm 21(2.18) weeks P < 0.01 ; the presencc of coeliac lymph nodes--present 19(3.6) weeks Vs absent 34(10,3) weeks. P < 0.05: the presence of metastases--present 1611.7) Vs absent 26(4.2) weeks. P < 0.04: Patients with squamous carcinomas survived longer but the difference was not significant. Survival was not dependent on the grade of turnout, the sex of the patient or the level of the tumour. The dysphagia score improved significantly after the procedure from a mean of 1.5(0.1 ) to 1.2(0.2). P < [].172_.There were no deaths as a direct result of the procedure and only one patient suffered aspiration pneumonia which settled with antibiotics. In summary the technique of high dose remote controlled afterloading has a definite role in the palliation of patients with oesophagcal carcinoma. It is well tolerated by the patient, and is associated with a low morbidity and an acceptable survival in combination with EBR.
Prospective evaluation of the training and practice of a nurse flexible sigmoidoscopist M. A. P. Hughes, P. J. Drew, R. Farouk, J. R. T. Monson and G. S. Duthie The Unit'ersit.r ~1 Hull .,Icadenlie Surgical LInit. Castle Hill Hospital. Hull HU16 5JQ. UK The introduction of flexible sigmoidoscopic screening for colorectal cancer would oven.,helm the medical endoscopy service. One solution is the introduction nurse endoscopy. This study represents the initial investigation into the results of the first ENB recognised nurse endoscopy service in the U.K. The nurse was trained in four stages. Stage I: Visuospatial orientation on a colon model and observation of 35 sigmoidoscopies. Stage 2: Supervised
Abstracts withdrawal of tile sigmoidoscope in 35 patients. Stage 3: Supervised performancc of 35 examinations. Stage 4: Independent practice with a consultant endoscopist on site but not directly supervising the procedure, Endoscopies were video recorded and reviewed by it consultant endoscopist and every patient also underwent bariunl enenla examination. Eight-seven independent flexible sigmoidoscopies have now been performed. "l-he mean duration of the exuminations was 10.5 minutes and the mean length of colon examined wits 52.2 cm. The exanlination was considered incomplete in 17 patients due to discomfort In = 3). inadequate preparation (n = 9) or stricture In = 5). Thirty eight of the completed exanlinations were nornlal. Tile results of tile abnormal examinations are shown below:
Pathology
Divcrticuhtr disease
Benign Polyps
IBD
Cancer
21
21
7
3
N umber
No pathology was missed by tile nurse cndoscopist during tile period of tile study. We conclude that, with adequate training, a nurse endoscopist is able to provide a safe and efficient flexible sigmoidoscopy service,
699
pool of 5 heahhy volunteers and 8 patients with metastatic cancer. In vitro spontaneous PBMC TNF production {WEHI bioassay), PBMC IL-2 product[on (CTLL-2 bioassay) in response to PHA, serum CRP and albumin. percentage weight change over the previous 6 months. LBMI and BMI (calculated from indices of height and weight), and survival of patients with cancer were documented, Significant levels of endotoxin were found in 4/5 volunteers (median. range) 14,1 6.5 pg; ml) and 5/7 patients with cancer ( 18,2 27.5 pgmll) and spontaneous TNF production in these subjects wits 44,39 21)8 pg.'ml (volunteers) and 121,16 267 pg/ml (patients). Neither the levels of endotoxin nor tile amount of PBMC TNF production correlated with CRP, albumin, weight change. BMI. LBMI, or white cell count (WCC). Tile index. TNF,,I L-2, multiplied by tile levels of circulating endotoxin in the nine subjects with evidence of endotoxaemia correhtted with CRP {R = 0.72, P = 0.03), albumin (R = 0.88. P = I).002). CRP;albumin (R = I).78, P = 0.013), WCC [R = 0.67. P = 0.05). weight change (R = 0.88, P = 0.01L BMI [R = 0.88, P = 0.001 ) and LBMI (R = 0.77. P = 0.016) despite considerable overlap in all of these parameters between the patients and volunteers, Tile clinical inlpact of endotoxaemia may be influenced by tile degree of impairment of lymphocyte Ik-2 production, tile spontaneous production of TNF and the levels of circulating endotoxin. (IL-2: interleukin 2, PHA: phytohaemagglutinin. BIVlI: body mass index. LBMI: lean body mass index. CRP: C-reactive protein. WCC: white cell count, PPMC: peripheral blood mononuclear cell, TNF: tumour necrosis factor, R: Spearman correhttion coefficient. WEHI. CTLL-2: cell lines)
IBD = Inflammatory Bowel Disease. ENB = English National Board
An evaluation of the laparoscopic approach to total mesorectal excision J. E. Hartley, A. Qureshi, R. Farouk, A. W. MacDonald, G. S, Duthie, P. W. R. Lee and J. R. T. Monson
The Universit)' O/ Hull Academh' Surgical Unit. Casth' Hill Itospital Cottinglum, North Humherside "HUI7 5JQ. UK Routine TM E in the trealnlent of low rectal cancer Ims produced tile lowest reported rates of local recurrence. In most laparoscopic-assisted anterior resections tile pelvic dissection is performed during the open phase of tile operation. Therefore. real doubt remains its to tile ability of a pure htparoscopic rectal dissection to achieve TME. In this stud',, all patients undergoing curative surgery with TIVlE have been studied prospectively in a nonrandonlised tashion - all taparoscopic procedures were perfc, rmed by it single surgeon and conventional resections by it second consultant colorectal surgeon. Tile age. sex and median Dukes' stage of tile two groups were comparable. Histological examination of tile resectcd specimens was performed by it single colorectal pathologist, blinded to the method of resection, according to standard techniques. Results are presented as median value with interquartile range.
Group (n) LAP [131 OPN(12I
Specimen length [cmI
Long, nlargin Icm)
Radial margin (cml
No. of positive margins
Lymph node yield
25.0 16.5] 28.5 111.0)
3.5 12.251 3.0 tl.5)
1/.6 10.851 1.0 11.21
0
7.0 15.0) 10.0 14.51
0
These preliminary data confirm the technical feasibility of achieving TM E perfornled exclusively laparoscopically, and suggest that immediate cancer clearance is not compromised. Further follow-up is required to determine the consequences for bladder and sexual function of this approach. Oncological safety will be assessed by long term Iocoregionul recurrence rates. OPN = Open LAP = Laparoscopic TME = Total mcsorectal excision
Decreased IL-2 and increased TNF production by human mononuclear cells may facilitate an exaggerated response to circulating endotoxins D. B. Gough*, K. C. H. Fearon'l',S. D. Heys* D. C. Cartert and O. Erendn* *Department q/'Surger)'. University o/"Aherdeen. and TDepartment o/Surgerv. Royal h¢/irmarl" qf l:~linhurgh. UK Endotoxaemia in humans is associated with an acute phase re~iponse, but levels of endotoxins do not relate to the severity of this response. TNF is thought to mediate the effects of endotoxins. Sensitivity to cndotoxin and TNF is increased in the cancer state. This may account for tile lack of correlation between clinical outcome and levels of TNF and endotoxin. We examined whether an index (TN F/I L-2), incorporating tests of lynlphocyte function and spontaneous mononuclear activity [PBMC IL-2 production and basal PBMC TNF production, respectively], might reflect the extent of the inflammatory response to endogenous endotoxin. Blood was drawn from a
Core biopsy improves pre-operative diagnosis of screen detected breast cancers J. Kollias, d. C. Litherland, A. J. Evans, A. R. M. Wilson, S. E. Pinder, C. W. Elston, I. O. Ellis and R. W. Blarney Brt,ast ScreeHing Training Cettlre. Cil)" Hospital. Nottitt,fhant. UK Surgical QA guidelines recommend over 70% of screen detected cancers be diagnosed preoperatively by cytology or core biopsy. The Nottingham Breast Screening Unit introduced core biopsy in breast screening assessment in April 1994. The aim of this study was to assess tile impact of introducing core biopsy on the preoperative diagnosis rate. Between April 1994 and March 1995, 100 cancers were detected. Fine needle aspiration cytology (FNA) and core biopsy results were reviewed to assess tile contribution of each to preoperative diagnosis rate. A comparison was then made with results from the previous 2 years.
FNA Alone invasive cancer in-situ cancer all cancers
74% 36% 70%
FNA + Core biopsy 94°/, (P = 0.0002) 82% IP < 0.01) 91% [P < 0.002)
Conclusion Tile introduction of core biopsy has signilicantly improved our preoperative diagnosis rate of screen detected breast cancer.
Comedo DCIS is hormone independent and will not benefit from antioestrogen therapy P. A. Holland, W. Fiona Knox*, Elizabeth Andersont, C. S. Potten:l:, A. D. Baildant, A. Howell and N. J. Bundred Depts of Sltrgery *Pathology. tMedical Oncolog.v. ++Epithelial Biology. IVithhtgton Hospital. M20 8LR. LIK The value of oestrogens in preventing recurrence of screen-detected DCIS after local excision is currently being studied. Using u novel animal model for human DCIS, the effect of oestrogen on DCIS cell proliferation rates has been studied using the Ki-67 antibody. A concurrent study of 50 archival DCIS lesions has shown comedo DCIS to have significantly higher cell proliferation rates [Median 14.7%, range 7-29%), than non-comedo DCIS [median 5.3%. range 0.5-19%, P < 0.001). For each experiment, 8 human DCIS xenografts were implanted into each of 8 nude mice, Half the mice were stimulated with a 2 mg 17/~oestradiol imphmt. Grafts were removed at 14 and 28 days. ER status was measured immunohistochemically. In 3 noncomedo [ER positive) DCIS lesions, oestrogen stimulation increased cell proliferation compared to DCIS in control mice. There was no increase in cell proliferation rates of 9 comedo (ER negative) DCIS lesions after oestrogen stimulation (see table). Over 50% of screen detected DCIS lesions are comedo subtype which are usually ER negative. These lesions were not stimulated by oestrogen and are oestrogen independent. Antioestrogen therapy is unlikely to benefit patients with comedo DCIS. DCIS--Ductal carcinoma in situ; ER--Oestrogen receptor Statistics by Mann Whitney U and Kruskal Wallis tests.
Abstracts
700
Comedo (9) All ER - v e Range Noncomedo 13) All ER + ve Range
Median Ki67 Day 0
Median Ki67 Day 14
Median Ki67 Day 28
25,88%
24.50%
22.70%
mm respectively). Our experience saggests that MR is a promising imaging technique for evaluating ILP.
P = ns 12.8--45%
10.3-55%
9-50%
2.07'/0
13%
10,11%
1.8-5%
11-15%
7-10.4%
D. A. Browell, Jane E. Liston, M. J. Egan and M. J. Higgs Breost Screening Centre. Queen Eli:aheth Hospital. Gateshead. UK P < 0.02
Digitization improves mammographic assessment of breast cancer K. Ogston*, P. Undrill't, G. Needham+, F. Gilbert,, S. D. Heys* and O. Eremin* Department.~ of *Surger)'. "~Biomedieal Ph.rsies. and ~Radiolog.r. Unirersit.r O/ .4berdeen. UK The best nlcthod of assessing breast cancer response to chemotherapy has still to be established. Computer assisted digital techniques may help in the interpretation of sequential nlanlnlograms and responses to treatment. Images were obtained from patients with breast cancers (T2(>4 cm). T3. T4: N2) treate~ with nco-adjuvant chemotherapy. Mammograms were perfornted at diagnosis and after completion of chemotherapy. Films were digitised on a LUMISCU 100 scanner at 400 microns resolution over an optical density range of 0 to 3.8. Each series of films were corrected Ibr variations in exposure. compression of the breast and patient position. Tile optical density of the whole breast and tile tumour area ',,,,ere determined asing the ANALYZE imaging software. Twenty-seven patients 1124 evaluated) who had a mammographic static response ",,,,ere identilicd. Twelve (44%) had a decrease in tumour density and 15 (56'%) no change. In the group with a density decrease, 10 (83"/0) had a clinical response (partial. complete) and 9 (75%) a good pathological response Iminimal residual disease). In tile group with no change in density. 5 133'!;.) had a clinical response and I (6%) a good pathological response. In 9 patients with good pathological responses and stasis on mammography, all shov,,ed a decrease in the density of the turnout.
Clinical response No clinical response Good pathological response Poor pathological response
Can touch print cytology reduce the need for further surgery in breast conservation
Density change (n = 12)
No density change (n = 15)
I0 2 9 2
5 10 I 14
Mammographic digitisation can improve substantially the interpretation of images in patients receiving chemotherapy.
Magnetic resonance (MR) guided interstitial laser photocoagulation in breast cancer H. Mumtaz, Margaret HalI-Craggs*, T. Davidson, M. Kissin'l',M. Payley*. I. Taylor and S. G. Bown+ + ~Natioual Medical Laser Centre, Departtnents qf Surger.r aml Imaghlg, U('L Medical School Lomhm and +Royal S,rre)" Count)' Hospital. Guih(lbrd. UK Interstitial laser photocoagulation (ILP) is a recently developed minimally invasive procedure for in situ tumour destruction. Its current limitation is the lack of an optimal imaging technique to demonstrate treatment effects. This study was designed to assess the role of MR in the development of ILP as a minimally invasive treatment of breast cancer. Twenty patients with breast carcinoma underwent M RI using a dedicated breast coil at I Tesla prior to laser treatment. M R images were acquired using a TI-weighted gradient echo sequence before and after enhancement with gadolinium. ILP was undertaken using a semiconductor diode laser for a duration of 500 sec. Under local anaesthetic, single (n = 17) or multiple (n = 3) 400 pm fibres were passed percutaneously through 18G needles into the centre of the lump with ultrasound guidance. Post-laser MR scans were performed at a median interval of 48 h (range 4-96 It). Following resection, the extent of disease, size of laser burn and residual turnout were correlated with MR images. The maximum size of the bright region seen on ultrasound correlated poorly with the extent of laser-induced necrosis. M R performed at or > 24 h post-laser showed a non-enhancing zone which correlated with laser-induced necrosis seen histologically. The median size of laser burn was I I mm measured by both MR and histological mapping (range 8-18 mm and 8-15
Conservative surgery with adjuvant radiotherapy gives equivalent results in terms of long terrrl survival. Adequate excision ill breast conservation is essential as local recurrence is a consequence of inadequate surgery. HisIological assessment may miss excision margin involvement. This study aims to ewduate touch print cytology (TPC) in assessing adequate excision margins. Histologically involved excision margins was the determinant thai led to farther surgery. Two hundred and lift.',' breast biopsies from one surgeon (MJIt) ',,,'ere analysed. Touch prints of tile fresh specimen were made on glass microscope slides. Cytological reporting was pcrfornlcd without prior knowledge of the biopsy result. Thirty-nine benign biopsies gave no lalse positive results. Forty-five have positive touch print cytology. Thirty-four had further surgery, twenty-six of which contained residual disease. Of those with a positive TPC thirty-eight had a resection margin of less than 5 ram. If the original resection margin was less than 5 mm and TPC was positive seventy-three percent of re-excisions contained residual cancer (positive predictive value pp,,,). If the original resection margin was less than 5 mm and TPC was negative only two had residual disease (ppv 3.5%). This shows that with negative TPC and a resection margin of less than 5 mm it is unlikely that residual disease remains.
Examining microvessel quantification and prognosis in invasive breast
cancer L. Marlin, C. Renshaw, B. Green, J. Winstanley and S, J. Leinster D~TJartments ¢~l Surgery mul Pathology. Unirer.~ity q! Lh'erpo,d, UK Studies on neo-~tscularisation as a prognostic factor in breast cancer have produced variable results. This may be secondary to differences in the methodologies. The aims of this study were: ( I ) to validate whether the microvessel density is a prognostic factor in breast cancer (2) to determine the best method for the quantification of the inlra-tumoural mierovessel density. Sections from 166 archival primary breast cancers were labelled with 3 monoclonal antibodies to vascular endothelium: anti-CD34, anti-CD31 and anti-FVIIIRAg, and then counted at 200 x magnilication over 10 liclds. To compare the 3 antibodies and the counting methods, the highest count and a mean of the highest 3. 5 and 10 counts for each antibody were correlated with survival. CD34 was the most sensitive endothelial marker (mean count CD34 = 83. CD31 = 78, FVIIIRAg = 65). There was a strong correlation for counts between all 3 antibodies (P < 0.001 Spearman rank test). CD34 is the best predictor of survival (P < 0.04 log rank Kaplan Meier survival analysis). For all the antibodies the highest and mean of the highest 3 counts gave the best prognostic information. We conclude that the microvessel count is a prognostic indicator in invasivc breast cancer. Anti-CD34 gives the best prognostic information and the highest count should bc used.
Does magnetic resonance mammography improve the detection of multifocal breast cancer? Joanna B. Reed, A. Coulthard, Alice Burridge, Jane Potterton, B. Angus and T. W. J. Lennard Depurtnwnts of Surgery and Radiology. University ~1 Neweasth" Medic',l SchoOl. Newcastle upon 7~vne. UK A cohort of 24 consecutive patients with a diagnosis of breast cancer on line needle aspiration underwent mammography, ultrasonography and Magnetic Resonance Imaging using standard protocols prior to surgery and the resahs were correlated with the pathological lindings. I I of tile 24 patients showed a single focus of carcinoma on all three imaging modalities. The other 13 patients all showed a further abnormality on the MRI scan suggestive of mullifocal nlalignancy and 9 of these were confirmed on histology. Tile 4 patients with false positive MRI scans for multifocality all had abnormalities on both mammogram and uhrasound suggestive of benign disease which was confirmed on histology. Of the 9 patients with a second focus of malignancy none were visualised on mammography and only 4 were visualised on ultrasound scanning. Thus 5 of the 24 patients, or over 20%, had a second focus of malignancy which was not detected on any other modality and which affected the suitability of local resection as an option for surgery. Failure to detect multifocal disease may be a factor in tile high rates of recurrence lifter conservative treatment for breast cancer. M RM = Magnetic Resonance Mammography
Abstracts M a g n e t i c resonance m a m m o g r a p h y in the investigation of suspected tamour recurrence following breast conserving treatment G. Needham*, F. J. Gilbert*, A. D. Murray*, T. W. Rcdpath~, S. D. Heys++, A. K. Ah-Sce~ and O. Eremin DtTartmems r~/ Radiology*. Biomcdica/ Physics't. and Surgery~.. Unirersity of ..Iherdeen. UK Suspected [unlour recurrence in Ifie surgically conserved breast often poses diagnostic difficulties. These may not be resolved by clinical examination. imaging (mammography. ultrasound) or fine needle aspiration cytology or core-biopsy. Resultant surgery to establish tbe diagnosis, adds further to patient anxiety, may result in breast disfigurement and induce more scar Ibrmation. There is a need. therefore, to evaluate new diagnostic modalities. Dynamic gadolinium (Gd) enhanced magnetic resonance mammography (MRM) has been recently introduced into clinical practice. We have used M RM to evaluate 37 consecutive patients who had undergone breast conservation treatment and who had clinical and or imaging (mammographic) suspicion of recurrent disease. Time from original treatment was I 10 years. MRM was performed on a Magnetom Impact 1.0 Tesla (Siemens}. using a double breast surlace coil. Both breasts were imaged in tbeir entirety in the axial plane with a pre-Gd-enhaucement and three post-Gd-enhancement repetitions. Total imaging time was under 20 minutes. Enhancing lesions were identified using image subtraction software (MammaCalc, Siemens) and sites of maximum enltancement ',','erequantitatively analysed using the indices AS, and AS,,,,,.
IS~ -S,,) AS~ = 0._~(F,,+I:~)
IS~, -S.} and
AS.....
fl.SiF,,+ F,,,.,,}
Lesion signal change is expressed as a fraction of the mean lat signal, with S.. S~ and S,..,. being lesion signal intensity pre-Gd, one minute post-Gd and at maximum enhancement. F,,. I:~ and Fro.,, are the respective signals from a region close to the lesion. Eleven patients (11 mammographic. I clinical abnormalities) had enhancing lesions. All lesions ~'ith AS~ > ¢1.30 (5; I I patients) had invasivc cancers (confirmed by biopsyl. Lesions with ASt < 11.30 16 I I patients) had benign disease Iconfirmed by cytology, biopsy). In one palienl an occult contralateral cancer was found. Tbe remaining 26 patients showed no enhancement, diagnosis confirmed by negative biopsy (3), negative cytology (I 7} or clinical and imaging lbllow-up (61. Quantitative M RM is helpful in discriminating recurrent from post-treatment change in the breast and tbe index ASt < (I.31)was an accurate predictor t 100%) of the absence of turnout recurrence in our series.
Plasma osteopontin correlates with survival in metastatic breast cancer H. Singhal, D. S. Bautista, Katia S. Tonkin, Frances P. O'Malley, Ann F. Chambers and J. F. Harris Lomhm Rcgiomd Cancer Ccmre. and Unh'crsit.r qf II "estern. Ontario, Lmuhm. Ontario. ('(llltl(kl Osteopontin (OPN} is a multifunctional glycosylated integrin binding phospboprotem, the levels of whicll have been shown to be elevated in metastatic cancer. This study was designed to prospectively test the prognostic utility of plasma OPN in metastatic breast cancer. Using a quantitative capture ELISA developed in our laboratory we measured plasma OPN levels in 56 women with known metastatic breast cancer attending the London Regional Cancer Centre. All patients were prospectively followed after measurement of plasma OPN. Patients with metastatic disease had levels from 26-485 ngml (median 84 ng/ml). At a median Ibllow-up of eight months. 18 patients bave died of metastatic disease. The median plasma OPN m the survivors is 67 ngml compared to 128 ng;ml in tbe deceased patients {P < 0.008. Mann-Whitney lest). Statistical analysis was performed using the log rank test of Kaplan Meier survival curves. A significant difference in survival [P < I].03, log rank test. hazard ratio 0.38) is evident for groups with values above In = 19) and below (n = 36} 100 ng~nal. Tbe results are even more signilicant when analysed with patients separated into quartiles, based on plasrrta OPN levels IP < 0.0081, with a very significant trend of decreased survival in patients with the highest levels (P < 0.0001 ). Tbe correlation of plasma OPN with survival in this initial study suggests the potential of plasma OPN to be used as a prognostic marker in metastatic breast cancer.
Cancer registry statistics for purchasers--can the partially sighted lead the blind? F. D. Skidmore Department of Surger.r. Joyce Green Ho.~7~ital.Dartlord. Kent. UK At patient presentation to bospital, demographic information, age. sex. occupation, inberitance factors, and clinical data. histology, nature of surgery and outcome is conscientiously recorded by medical staff. Regional Cancer Registries (RCR) have relied on a "top down' philosophy for capturing data based on death certificates, and erratic searches of some hospital records by inadequate numbers of peripatetic clerks. (i) Recent analysis of one consullant's solo rectal cancer records revealed that the RCR had only captured
701
70% of these patients 5 years after presentation. Purchasers. RHA remnants and DOH rely on RCRs for data against which expenditure on cancer management and staffing predictions are calculated, lit) Cancer specialists who press government to create more posts and a cancer centre network must arrange for immediate reporting of statistics and histology to RCRs. Purchasers must be advised to insist that providers have cancer data managers working with clinicians. (iii} The present incomplete figures for cancer incidence at District level should be compared with cancer numbers identilied after inception of a 'bottom up" approach Io data collection in order to correct under estimates of true workload and inadequate expenditure projections by the Department of Health.
References (i) "Review of Cancer Services in South East Thames 1991 1992" SETRHA 1994 {it) 'Medical Manpower & Workload in Clinical Oncology in the U.K.' Royal College of Radiologists 1991 lilt) 'Core contract for cancer registries" NHS Executive 1995
The application of neural networks to prognostication in colorectal cancer
P. J. Drew, L. Bottaci*, R. Farouk, P. W. R. Lee, I. M. C. Macintyre'l', J. R. T. Monson and G. S. Duthie The Unicersit)" ¢~fHtdl ..Icademic Surgical Unit. Casth' Hill Ho.sjTital. * Departmerit of ('ompltlcr Sch'nce. Hull aml "~TIw IVeslern General Ho.qJital. Edinburgh. UK The prediction of survival following surgery for colorectal cancer is unreliable. Even the best of the pathological staging techniques, such as Dukes', are only able to give percentage survival figures relating to the popuhttion as a whole over set periods of time. Expert systems and artificial intelligence programmes have previously been tmable to provide a consistently superior performance. Neural Networks. which are able to "learn' from established outcome data. represent an alternative form of artificial intelligence. Emulating a biological systems" computational techniques I'a~.ditatesa level of flexibility and accuracy of pattern recognition impossible to achieve with conventional systems. We investigated the ability of neural networks to prognosticate for individual patients Ibllowing surgery for coloreetal cancer. Unselected 5 :,,ear follow up data on 334 colorectal cancer patients was used to teach and validate the networks. Several network designs were constructed: 41 input parameters made up the first layer of neurons, 12 15 neurons were utilised in tbe middle layer with the output neuron providing a yes 11o answer. The networks achieved an accuracy of greater than 80% Ibr the prediction of cause specific mortality from colorectal cancer at 9. 12. 15, 18.21 and 24 months. These results far exceeded the capability of the traditional Duke's staging to predict survival. The networks were able to accurately predict, in 3 monthly periods, the duration ofsurvival of individual patients and not just tbe population group to which tbey belonged. As they are provided with more data and 'learn" more about the disease, the accuracy of the networks' predictions will increase still furtber. We conclude that this technology may soon allow accurate individual prognostication in colorectal cancer.
Apoplosis, p53 expression and prognosis in colorectal cancer N. E. I. Langlois't, J. Lambt, O. Ereatin* and S. D. Heys* Department of *Surgery and tPlltholog.v. Uniccrsity ~/' .4hcrdcen. Aberdeen. U'K Interest in tbe control of tumour growth has focused on the relationship between cell proliferation and cell death (necrosis and apoptosis). The protein product of p53 has a key role in inducing apoptosis. Normally. the turnover of the p53 protein product is rapid and the protein is not detectable by immunollistochemistry. If detected it is probably mutant and non-functional. The aims of study were twofold. (a) to examine the relationship of apoptosis, mitosis and the expression of p53 mutant protein product in colorectal cancers, and (b) to evaluate their roles as prognostic l:actors, in conjunction with known prognostic indicators such as Dukes stage and ext~mlural vascular invasion. The turnouts from 75 patients with coloreetal cancer aged 45 years and under, were staged using the Dukes system. Apoptotic and mitotic counts and the presence of extramural vascular invasion were determined by light microscopy using standard criteria. The protein product of the p53 oneogene was determine using a streptavidin-biotin technique (CMI antibody). Tumours were regarded as positive if there was a 10% or greater staining of turnout nuclei. A significant correlation ;,,'as observed ber,veen apoptotic count and the mitotic index [r = 0.86; P = 0.003 (Fisher's r to z)]. In addition, the mean apoptotic count was increased in lumours not expressing the p53 product (mutant protein), when compared with those in v,,hich it was detected [5.7 versus 4.3, P = 0.02 (unpaired t test)]. There was, however, no relationship between p53 expression and mitotic count. Independent risk factors (muhivariate analysis) for overall survival were as follows: apoptotic count (P < 0.04), Dukes stage (P < 0.0001). extramural vascular invasion
702
Abstracts
(P < 0.02), (Cox stepwise proportional hazards model). This study has identtiled that apoptotic count is an independent prognostic indicator in col,rectal cancer. Furthermore, these results suggest that p53 protein (functional) may have a key role in inducing apoptosis in these ttunours. The possibility that restoration of p53 function may improve survival has implications for gene therapy of cancer.
Management of Ioco-regional recurrence in patients with colorectal liver metastases treated by hepatic artery infusion chemotherapy M. M. Davies, Carol Fordy, Sally Earlam and T. G. Allen-Mersh Department q/'Surgery. Charingcross & II "estminster Medica/ School. Chelsea & ll"estminster Hospital. Lomhm. U'K Abdominal and pelvic LRR is known to develop in patients with CLM being controlled by HAl. WE report the results of LRR treatment by resection or irradiation in a population of 147 patients undergoing HAl Ibr CLM. Twenty patients [14%) developed abdominal (7 patients) and/or pelvic ( 13 patients) LRR. Treatment of LRR was feasible in 15 of these patients (resection 6 patients: 4 abdominal, 2 pelvic; pelvic irradiation 9 patients). The survival from onset of HAl in LRR patients (median 403 days. i.q.r. 236-584 days) was not significantly different (log rank test) from patients who did not develop LRR (median 272 days, i.q.r. 167 -323 days). Median survival from treatment of LRR was 182 days, i.q.r. 102 430 days [resection 259.5 days i.q.r. 172-388 days. irradiation 155 days i.q.r. 129-170 days). Control of LRR by resection or irradiation was feasible in 75% of patients developing LRR and resulted in similar survival to that in CLM patients treated by HAl who did not develop LRR.
T h e p e r i v a s c u l a r innervation and ultrastructure of blood vessels in
liver metastases in an animal model S, Ashraf, Marilena Loizidou, Rahima Crowe, M. Turmaine, I. Taylor and G. Burnstock Departments o/ Surgery aml Anatomy. UCL Medical School. Lomhm. UK We have previously demonstrated abnormal innervation of blood vessels in human col,rectal liver metastases. This information is being utilised to enhance cytotoxic perfusiou of liver inetaslases. To detcrrnine the optinlunl (lose of drug and pharmacological moduhltor, we have investigated MC28 fibrosarcoma and HT29 aden.carcinoma introduced intraportally in the rat and which result in multiple liver metastases. Areas of normal liver and liver metastases were studied immunohistochemically for the presence of protein gene product 9.5 (PGP), neuropeptide Y (NPY), tyrosine fiydoxylase [TH). calcitonin gent-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and substance P (SP). Perivascular innervation and tfltrastructure of blood vessels were also examined by transmission electron microscopy. In both models within the normal liver perivascular nerve fibres containing PGP. NPY, TH. C G R P and SP were observed around the inlerlobular blood vessels and in the portal tract. The highest density was seen for PGP, In contrast no perivascular immunoreactive nerve was seen either in tile MC28 or HT29 liver tumours. Similarly electron microscopy confirmed the absence of perivascular nerves in the HT29 turnout, Smooth muscle cells were not observed in any turnout blood vessel. These results demonstrate similarity with human col,rectal liver metastases and indicate that this model is suitable Ibr pharmacological studies on vascular manipulation of hepatic artery infusion chemotherapy.
Response to regional chemotherapy in patients with variant hepatic
LRR = Iocoregional recurrence HAl = hepatic artery infusion CLM = col,rectal liver metastases
a r t e r y anatomy Julie C. Doughty, H. Warren, J. D. Anderson, T. G. Cooke and C. S. McArdle
Unirersity De'purtnwnt ~!/'Surgery. Glasgow Royal h!/irmar.v. Ghtsgow. G31 2ER. UK In-vitro assessment of Lipiodol-cytotoxic conjugates fur primary and metastatic liver cancers R, AI-Mufti, B. Chauhan*, H. Farrent*, C. Trefiane*, K. E. F. Hobbs and M. C, Winslet University D~Tartment t!l' Surgery. Royal Free Hospital School ~,/ Medichu,, *Pharma~T D~Tmrtment. Pond Street. Lomhm. NIl'3 2QG. UK Lipiodol. an iodinated ethyl ester derivative of poppy seed oil, has been used as a therapeutic vehicle to deliver targeted chemotherapy or radiotherapy for primary and some metastatic liver cancers. Variable cytotoxic conjugates have been used with little prior assessment in vitro or vivo. The efficacy and stability of Lipiodol-cytotoxic conjugates with Epirubiein, 5-Fluorouracil, Methotrexate and Milomycin-C were assessed in cell cultures of Hep-G2 Ihuman hepatoma), H UVEC (human umbilical vein endothelial cells), SW620 (coin-rectal metastatic cancer) and LoVo (coin-rectal hepatic cancerl cell lines. The cytotoxicity effect of these Lipiodol conjugates was assessed with regard to cell growth, cell viability with trypan blue exclusion and LDH assays. The dose-response curves used were equivalent to the clinical doses used for each cytotoxic agent. The cultures were exposed to these Lipiodof cytotoxic conjugates for 3.6. 12, 24 and 48 hours. Suspension stability '.','as assessed by separation on standing at room temperature. LipiodoI-Methotrexate and LipiodoI-Mitomycin-C separated completely at 2.5 hours, LipiodoI-Epirubicin at 3.5 hours, followed by Lipiodol5-Fluorouracil at 4.5 hours. Cell growth analysis of the HUVEC cell line showed that these Lipiodol-eytotoxic coujugates were cytostatic on nonmalignant cells, with a high retained percentage viability. All four Lipiodolcytotoxic conjugates had a significant cytotoxic effect on the three cancer cell lines at 24 hours with a maximum efl'ect at 48 hours. The optimum Lipiodob cytotoxic conjugate was Epirubicin. which was effective against all the cancer cell lines, followed by 5-Fluorouracil.
48 HOURS
Control cells
Hep-G2 SW620 LoVo H UVEC
Regional chemotherapy via surgically implanted hepatic artery catheters is increasingly used to treat patients with col.rectal liver metastases. Up to 40% of patients have unusual vascular anatomy. It is suggested that this ulay compromise outcome and the aim of this study was to compare the response of patients with normal anatonly to those with abnormal configurations. Forty-five patients with biopsy proven liver metastases who were subscquently treated with intra-arterial 5Fu and systemic folinic acid had preoperative angiograms and the anatomy confirmed at laparotomy. Patients with normal anatomy had a silicone catheter inserted into the gastroduodenal artery and those with variant anatomy had the less domiuant vessel temporarily occluded and pcrfusion assessed with patent bluc dye. If perfusion was inadequate a second catheter was inserted into an accessory vessel using a sapbenous vein graft. Twenty-eight patients had normal and 17 variant anatomy. Response ,.','as assessed by CT scan at 3 and 6 months.
Normal Variant
Complete response
Partial response
Stable disease
Progressive disease
2 2
I0 4
12 I0
4 I
No significant difference P > (1.6 (Chi-square) was observed between responders and non-responders in tile group. There was also no signilicant difference in time to progression and percentage hepatic replacement between the groups.
Control Lipiodol
LipiodolEpirubicin
Lipiodol-5Fluorouracil
LipiodolMethotrexate
LipiodolMitomycin-C
99%
98.5'/o
26.6"/o
98.5%
98. 1%
1.2%
63"/°
74.2%
76.5°/.
42%
61.3%
97. 1% 99.1%
96.3% 97.9%
25. 1% 92.5%
59.2°/.
20.7% 94.3%
68.5% 89.7%
76.2% 81.5%
Abstracts We conclude that variunt hepatic artery anatomy does not alter the response Io regional chemotherapy.
703
Malignant ascites : a two year experience in a teaching hospital S. L. Parsuns, M. Lang and R. J. C. Steele Department o/Surger.r. I- Floor. II'e:~'thlock. L,'nirt,rxit)' Hospital. Nottingham.
NG7 2L'H. UK O m e p r a z o l e is not cytotoxie to eoloreclal cancer cells J. R. Duncan, L. D. Penman, Jane Plumb*, P. J. O'Dwyer and J. R. McGregor
('nirersity Dcparlmcm ~!/ Surgery. II'estt, rn h!/irmary and *('RC Beatsm~ Rcseurch Lahnrutorit,s. Ghtsgow. UK Omcprazolc induces signilicanl hypcrgastrinucmia and as gastrin is trophic lbr colonic mucosa there has been concern surrounding its long term prescription and colorcctal cancer risk. In contrast, n recent study suggested thai omcprazole can protccl against experimental carcinogenesis. Tile aim of this experiment was to delcrminc if omcprazolc has uny cytoloxic action on colorcctal cancer cells. Omcpruzolc (3.45 rag). dissolved in I M dimcthyl sulphoxidc (I roll wus serially dilulcd in culture medium to give concentrations ranging from 2 x Ill "~to 2.5 x 10 I ' mols,l. Maximal plasma levels after oral omcprazole in mun ure less than 5 x 10 " m o l s l I Rcgurdh CG. TIn'r~qwuth' Druy ,thmiloriny 1990: 12:163 72). Three hunlun colorcctul cunccr cell lines were studied: HT29. LoVo. and BE. Suspensions of 7.75 × I()'a cells were added to 4 mls drug-free medium in culture flasks. After 48 hours this rncdiurn was replaced with omeprazolc containing medium and left for 24 hours. Cells were then plated out and colonies counted at 10 days. Colony Ibrming cll~cicnc.v was low Ibr cach cell line [I I~.,, to 37".;,]. Omcprazolc hud no ell"cot ut its highest concentration when colony formation was reduced. At Iherapeutic levels omcpruzole does not suppress colorectul tumour cell proliferation. A cytotoxic action cannot therefore account for any protection omcpruzole offers against colorcctal carcinogenesi's.
Ascilcs is a manifestation of advanced malignancy and can be associated with a variety of primary tumours. One-hundred and sixty-four consecutive patients who develop ascites between April 1992 and Murch 1994 were reviewed. Ascitcs of ovarian origin wus associated with a significantly better survival than uscites from other causes (P < (I.0t)l using 1he Mann Whitney U test). Ascites in the presence of liver mctustuses was associated with a poor prognosis ( P .< 0.001 ). A serum albumin at diagnosis of > 32 g l wus associated with un improved surviwd (P < 0.001 ).
Tumour All Ovariun Gastrointestinal Breasl Unknown Misccllancous
Total no.
No. dead
Survival (days) median Irange)
164 46 48 16 37 17
147 32 47 16 37 15
42 (I 2798~ 287 {6 1913) 26 (I 236] 39.5 [7-349~ 40 (3-364) 57 {7-2798)
Mean age 65.8 63.4 67.5 53.4 72.4 65. I
Forty-live per cent of putients with uscites had ascites as their initial presentation. It is essential 1o investigate all female patients to identify all ovarian primuries, since these patients have a reasonable prognosis if treated appropriately. Rigorous investigation in male patients is not justilied.
Editorial Note. T h e Europeun .Iourmd ~/' Surgical Oncologt' is pleased to publish a b s t r a c t s p r e s e n t e d at the British A s s o c i a t i o n o f S u r g i c a l O n t o l o g y a n d E u r o p e a n Society o f Surgical O n c o l o g y meetings. In o r d e r to extend this a s s o c i a t i o n , the J o u r n a l offers a 'l~lst-track" p u b l i c a t i o n o f p a p e r s a c c e p t e d Ibr p r e s e n t a t i o n at B A S O o r E S S O meetings. I n d i v i d u a l s w h o s e p a p e r s h a v e been a c c e p t e d Ibr p r e s e n t a t i o n are invited to s u b m i t c o m p l e t e m a n u s c r i p t s to the J o u r n a l within I week o f the meeting. A system has been i n t r o d u c e d to e n s u r e r a p i d peer review a n d if the p a p e r is a c c e p t a b l e for p u b l i c a t i o n it will a p p e a r within three m o n t h s l¥om a c c e p t a n c e . Please note t h a t the p a p e r m u s t c o n l b r m to the strict criteria set d o w n by the European Journal qfSur.qical OncohLq.t'. W e h o p e t h a t a u t h o r s will take a d v a n t a g e o f this oiler. Irving Taylor
Editor-hl-Cllic~f