The importance of surgery and accurate axillary staging for survival in breast cancer.

AIMS: The purpose of this study was to investigate, within the context of the Danish Breast Cancer Cooperative Group (DBCG) programmes, whether a dedicated surgical approach had a significant bearing on the outcome of breast cancer treatment. METHODS: From 1 January 1980 to 31 December 1990, patients below 70 years of age with operable breast cancer from Odense University Hospital (n=743) were compared with those from the rest of Denmark (denoted rest-DK) (n=15,419). All patients were treated according to nationwide DBCG guidelines and reported to the DBCG Data Centre. The potential median observation time was 11.2 years (range 6.0-16.9). Patients underwent mastectomy or breast conserving therapy, and high risk lymph-node positive patients had adjuvant systemic therapy with or without radiotherapy. RESULTS: Comparing total patients series, overall survival (OS) was significantly superior in patients from Odense compared with rest-DK (P=0.02), with 10-year OSs of 62% (95% CI: 58-65%) and 56% (55-57%), respectively. In subgroups, the OS of low-risk node negative patients (protocol A) in Odense compared with rest-DK was significantly better (P=0.02); 10-year OS was 78% (73-84%) versus 72% (70-73%). Among the high-risk pre-menopausal patients (protocol B), the OS was significantly better in Odense (P=0.009); 10-year OS was 67% (60-75%) versus 53% (51-55%) in rest-DK. Post-menopausal high-risk patients (protocol C) did not differ significantly in OS between Odense and rest-DK (P=0.61). Locoregional control in the Odense series was superior compared with rest-DK. More lymph nodes were recovered and examined from the axilla in the Odense series than in rest-DK, a median of 10 vs. 6 nodes. In the Odense series, a significantly higher proportion of pre-menopausal patients had positive lymph nodes, predominantly one to three positive nodes, and subsequently a lower proportion of pre-menopausal patients had negative lymph nodes compared with rest-DK (P=0.02), indicating a more accurate staging in Odense vs. rest-DK. The survival benefit among the patients from Odense cannot be explained by stage migration alone, but seems to represent a true survival advantage. Overall mortality was significantly lower in the Odense series compared with rest-DK. Whether or not this difference could be explained by lower background mortality in the Odense series or was caused by superior treatment is discussed. CONCLUSIONS: The extent of surgery seems important for locoregional tumour control and accurate axillary lymph-node staging. In combination, these might lead to superior recurrence-free and overall survival, although differences in background mortality cannot be ignored. Surgery, therefore, might represent a risk factor by itself.

[Clinics for counseling on cancer genetics. Experiences with genetic studies and counseling on familial breast cancer and colorectal cancer]. / Cancergenetisk rådgivningsklinik. Erfaringer med genetisk udredning og rådgivning ved familiaer cancer mammae og familiaer cancer colorectalis.

Five to ten percent of cases of breast cancer and colorectal cancer are familial. These families can be divided into high-risk families and moderate-risk families. Cancer in high-risk families can often be explained by dominant inheritance of a gene causing increased susceptibility to cancer. There is a great demand for genetic counseling in these families, and the structure of and experiences from a familial cancer clinic at Odense University Hospital is described. The establishment of a familial cancer clinic involves three steps: 1) Identification of families with increased cancer susceptibility; 2) Molecular tests to identify gene carriers; 3) Clinical examinations for early detection of tumors. Achievement of these three steps requires the involvement of several medical specialties to ensure patient care. Experience with familial cancer clinics is still limited and the involvement of genetic testing and clinical examination programs at risk individuals are insufficiently examined. The rapidly improving techniques for genetic testing make it urgent that it is implemented as part of already established clinical programs.

The role of haematuria in the diagnosis of blunt renal trauma.

In order to reevaluate the indications for an acute excretory urography (IPV) after blunt renal trauma, with special emphasis on the degree of haematuria, the medical records of 114 patients admitted to The Department of Urology, Odense University Hospital during a 10 year period were reviewed. Fourteen cases of major renal damage were revealed. Thirteen of these patients had macroscopic haematuria. Three of the thirteen patients were in shock and required an acute operation in order to stabilize their blood pressure. In one case, a thirteen year old girl had a major renal lesion which was diagnosed by acute IVP before examination of the urine. The present data support other reports in the literature stating that radiographic imaging is not necessary in the adult sustaining blunt renal trauma with microscopic haematuria and no shock. However, we find good reason for radiographic evaluation of all children after a blunt renal trauma, independent of the degree of haematuria.

[Intravenous urography in blunt renal trauma]. / Intravenøs urografi ved stumpe nyretraumer.

In order to re-evaluate the indications for an acute excretory urography after blunt renal trauma, the medical records of 116 patients admitted to the Department of Urology, Odense University Hospital, during a ten year period were reviewed. Fourteen cases of major renal damage were revealed. Thirteen of these patients had macroscopic haematuria. Three of the thirteen were in shock and required an acute operation in order to stabilise their blood pressure. In one case, a 13-year-old girl had a major renal lesion which was diagnosed by acute excretory urography before examination of the urine. The present data support other reports in the literature stating that radiographic imaging is not necessary in the adult sustaining blunt renal trauma with microscopic haematuria and no shock.

[The duct ectasia syndrome--an overlooked disease entity]. / Duktektasisyndromet--en overset sygdomsenhed.

Mammary duct ectasia is a benign disease of the mammary gland, characterized by a frequently long history of tumour formation, nipple discharge, nipple retraction and mastalgia. Non-puerperal mammary abscess, which may be the presenting symptom, is also part of the syndrome. Diagnosis can often be made on the basis of the history and the clinical findings of nipple discharge, nipple retraction, tenderness on palpation, fistula formation and subareolar tumour/abscess formation. Mammography may guide diagnosis. Breast cancer is the most important differential diagnosis. If the clinical picture resembles cancer, it is necessary to perform diagnostic biopsy. Causal therapy of mammary duct ectasia is not available. Until now excision of the central mammary tissue and larger ducts has been used as treatment for the clinical manifestations of abscess, fistula and nipple discharge, apparently with good results.

[The duct ectasia syndrome. A prospective clinical study of patients with breast diseases]. / Duktektasisyndromet. En prospektiv klinisk undersøgelse of patienter med mammalidelser.

Mammary duct ectasia is a benign condition of the mammary gland histopathologically characterized by inflammatory changes in the collecting ducts. A prospective clinical and histopathological study was done of 316 consecutive patients with surgical mammary diseases. The syndrome of mammary duct ectasia (DES) was found in 42 patients (13%). The mean age was 44 years and 81% of the patients were pre- or menopausal. Forty-eight percent of the patients had a history of previous benign breast lesions and abnormality associated with lactation was also frequently represented in the history. Major symptoms were tumour formation, localised in the subareolar region in more than half of the cases, subareolar abscess and nipple discharge. Minor symptoms were mastalgia, mammary fistula, nipple retraction, general symptoms and enlarged axillary lymph nodes. Treatment for an abscess in DES seems to fail more often if only incision and drainage are performed. Excision of the entire focus and corresponding duct may prove to be better.

Needle biopsy of breast cancer. Appearance of tumour cells along the needle track.

Appearance of tumour cells along the needle track in patients with breast cancer diagnosed by SURECUT needle biopsy is found in two out of 47 consecutive cases. It is not known whether these cells are early implantation metastases or are harmless. To avoid any unnecessary risk to the patients, we recommend that needle biopsy is so performed, that it is possible to remove the track during the definite surgical procedure, and that penetration into the muscles of the thoracic wall during the biopsy procedure is avoided.

[Breast carcinoma in situ. Diagnostic and therapeutic aspects with special reference to growth patterns]. / Carcinoma in situ mammae. Diagnostiske og terapeutiske aspekter med saerlig reference til vaekstformer.

The probability of developing in situ carcinoma has been calculated at about 25%, while the cumulative risk of having the diagnosis established is estimated at less than 1%. In situ carcinoma in its pure form constitutes up to about 6% of all newly diagnosed breast cancers in clinical series, whereas its share in the most thorough mammographic screening series ranges from 8 to 16%. This excess in diagnosis comprises, in particular, the ductal type, primarily its most aggressive forms. To-day in situ cancer occurs chiefly as non-palpable lesions demonstrated by mammography or as minor changes discovered accidentally by the pathologist. A more recent classification based upon histological growth patterns is described. The advantage of classifying according to growth pattern bears a good correlation to clinical presentation, extent of surgery and prognosis. The treatment of in situ carcinoma lacks a rational basis. Therapy should therefore be kept within the framework of prospective protocols. Various treatment modalities are described with reference to the most important multicenter trials.

In situ carcinomas of the female breast. Diagnostic and therapeutic aspects with special reference to histological growth patterns. Clinical review.

There is a disparity between the autopsy prevalence and the clinical incidence of in situ carcinoma of the breast without co-existing invasive carcinoma. The probability of developing in situ carcinoma is about 25%, while the cumulated risk of having the diagnosis established is less than 1%. In situ carcinoma in its pure form constitutes roughly 6% of all newly diagnosed breast cancers whereas in the most thorough mammographic screening series the incidence ranges from 8 to 16%. This excess in diagnosis comprises the ductal type in particular, primarily in its most aggressive forms, while the lobular type is no more common than in clinical series. Today in situ cancers occur chiefly as non-palpable lesions shown on mammography or as small changes accidentally discovered by the pathologist in a meticulous examination of an otherwise benign specimen. This survey also describes the traditional histopathological classification and presents in more detail a new classification based on histological growth patterns. The advantage of classifying in situ cancer according to its growth pattern is that it shows a good correlation with its clinical presentation. Moreover, the growth pattern can indicate the extent of excision. In addition, the method also seems to be applicable to prognosis. The treatment of in situ carcinoma has not been worked out scientifically, so treatment should be kept within the framework of prospective clinical trials. This is the only way to collect useful data about the biological behaviour of such lesions. In several countries large multicentre studies are being conducted to extend our knowledge about carcinoma in situ and to create a rational basis for treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous urography with a new non-ionic contrast media in a clinical phase III study: iopentol vs iohexol.

The safety and diagnostic efficacy of iopentol 300 mg I/ml were compared with iohexol 300 mg I/ml in 300 patients submitted for urography. The study was carried out as a double-blind, randomised parallel study where 149 patients received iopentol and 150 patients iohexol. There were no significant differences between the patients receiving the two contrast media with regard to demographic parameters, rate of injection or total dose of injected contrast media. No changes in blood pressure and no clinically important changes in heart rate were detected in the two groups. No serious adverse effects occurred. Seven patients (5%) in the iohexol and 12 patients (8%) in the iopentol group experienced adverse effects other than a sensation of warmth. Fourteen iohexol patients (9%) and 18 iopentol patients (12%) experienced warmth related to the contrast injection. Excellent films were obtained in most patients and no difference in diagnostic quality between iopentol and iohexol was observed.

Multicystic transformation of the kidneys in dialysis patients.

In a dialysis population patients who had been treated merely with haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) were examined with ultrasound. The occurrence of multicystic transformation of the kidney was 4/15 in HD patients and 8/25 in CAPD patients with no significant difference between the two groups. There was a significant association between the occurrence of multicystic transformation and the patient age while there was no significant association to the duration of dialysis or the duration of the uraemic state. No tumour or any other complication to cystic transformation was found. In 582 persons without renal disease examined as controls we found 44 with cystic change. This material does not support the recommendation of regular ultrasound examination of our dialysis patients. However, until these results can be confirmed by prospective studies we must recommend screening of all maintenance dialysis patients after a longer duration of dialysis.

Diagnostic strategy in the management of patients with breast symptoms. A recommended design and present experience.

The diagnostic problems in patients with breast symptoms have increased as the referral pattern has changed. Patients with vague symptoms and atypical palpatory findings are increasing in number. At the same time, the doctor is faced with the demand for greater diagnostic accuracy and, paradoxically, restraint in the use of diagnostic methods. Accordingly, high priority must be given to an effective diagnostic strategy without unnecessary investigations and delaying procedures. Above all, efforts must aim at reducing the number of 'unnecessary' benign biopsies. We are presenting a suggestion for an integrated diagnostic system based upon close collaboration between the general practitioner on one hand and radiologist, surgeon, and pathologist as the expert hospital team on the other. This design has not only entailed greater diagnostic accuracy, it also complies with the demand for conservation of resources.

Bioptic strategy in breast cancer.

The bioptic strategy in breast cancer rests on the following basic conditions at the Department of Surgery K, Odense University Hospital: Firstly, clinical mammography precedes any bioptic procedure. Secondly, the bioptic procedure must secure representative tissue for histological examination. Thirdly, knife-biopsy should preferably be excisional. Finally, tissue examination is exclusively done by the pathologist and always on unfixed tissue. The application and outcome of the employed biopsy methods are illustrated by a series of 365 women with operable, primary invasive breast cancer, treated from 1982 to 1987. Definitive surgery was mainly based on excisional (62%) or needle biopsy (24%). Three-fourths of the patients were treated by the one-stage procedure. However, within the last year of the period the rate of needle biopsy and two-stage procedures was doubled, increasingly employing core-aspirating needle biopsy synchronously with mammography and done by the radiologist. So far, patient compliance and histological outcome is satisfactory.

In situ carcinomas of the female breast. Incidence, clinical findings and DBCG proposals for management.

In situ carcinomas of the female breast (CIS) include lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS). Also associated are controversial forms of epithelial hyperplasia, lobular cell atypia (ALH) and ductal cell atypia (ADH). Based upon recent Danish autopsy studies, it has been estimated that about 25% of all women will develop in situ carcinoma, predominantly in the form of DCIS. Only a fraction of these lesions will evolve into a clinical manifest form, however. Thus, in a clinical setting, the frequency of CIS is 0.09 cases per 1,000 woman-years for a Danish female population aged twenty years or more. The lifetime risk of having CIS demonstrated is estimated at 0.53% for women in this age group. CIS makes up a few per cent of all newly diagnosed breast cancers in Denmark. Enforced employment of mammography in the early detection of breast cancer will increase CIS incidence from about 4-6% to about 9-10% of all newly diagnosed breast cancers, and aggressive DCIS growths will mainly constitute the increment. In concurrence with the new DBCG protocols in 1988, new strategies for the management of in situ carcinomas, based upon histogenetic types and growth patterns, are being introduced. The aim will be breast-conserving treatment whenever it can be achieved.

Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies.

In 110 consecutive, medicolegal autopsies of young and middle-aged women (range 20-54 years) the breasts were examined by an extensive histopathologic method and by correlative specimen radiography. Malignancy was found in 22 women (20%) of which only one was known to have had clinical invasive breast cancer (IBC). At autopsy 2 women had IBC (2%), the remaining in situ carcinoma (in situ BC) of microfocal type (18%), i.e. 15 (14%) intraductal carcinomas (DCIS), 4 (3%) lobular carcinoma in situ (LCIS) and one (1%) both DCIS and LCIS. Forty-five per cent of the women with malignancy had multicentric and 41% had bilateral lesions. Forty-five per cent of all histologically confirmed malignant lesions were identified by specimen radiography. Adenosis, benign epithelial hyperplasia, papilloma and duct ectasia were positively associated with malignancy. In addition malignancy was significantly more frequent among women aged more than 40 years, with late age at first full-term pregnancy, with alcohol abuse and with steatosis or cirrhosis of the liver. The results suggest that clinically occult in situ BC are frequent in young and middle-aged women.

In situ carcinomas of the breast. Types, growth pattern, diagnosis, and treatment.

The paper presents a prospective study comprising 40 consecutive patients with in situ carcinomas of the breast and two with atypical ductal hyperplasia (ADH) who underwent operation during a 2-year period at a single hospital. Out of the 40 in situ carcinomas 13 were of the lobular type (LCIS) and 27 of the ductal type (DCIS). They made up about 9% of all newly diagnosed breast cancers. Histologically a distinction could be made between three different growth patterns: microfocal, tumour-forming, and a diffuse form. With the exception of one case, the 26 microfocal growths (2 ADH, 13 LCIS, 11 DCIS) were accidental findings in otherwise benign breast biopsies, whereas the tumour-forming and diffuse forms (16 DCIS) were diagnosed in the great majority clinically and/or by mammography. Of the tumour-forming and diffuse DCIS 25% were demonstrated solely by mammography. The surgical treatment in the 26 patients showing microfocal changes was exclusively biopsy in 23, while three had mastectomy, because of a papillary focus in two and patient preference in one. Of six patients with tumour-forming DCIS three had segmental resection and three mastectomy, the latter because of papillary foci, while all 10 with diffuse growth had mastectomy. On the basis of their experience of types and growth patterns, the authors set up a surgical strategy which might add new aspects to our knowledge about the biological nature of in situ lesions.