Biomedical subjects

F Hartveit

Publications and source records attributed to F Hartveit.

At least 19 recordsLinked to original sources

PubMed2000

'Missed' micrometastases--the extent of the problem.

The value of detecting micrometastases in patients with breast cancer has been debated for many years. The aim of this study was to determine whether and why such tumour deposits are missed at the time of reporting. The series comprised 272 patients treated surgically for breast carcinoma. For node-negative cases, the haematoxylin and eosin stained slides were re-examined. Those still remaining negative were stained with epithelial membrane antigen marker (EMA). Hilar sections were used in 76% of cases. Micrometastases were found in 35 cases reported as node-negative: 15 being identified on re-examination and 20 after staining with EMA, a gain of 44%, including 20 of embolic type. All were found in hilar sections of the nodes. The patients in whom micrometastases were found on further examination had significantly smaller tumour deposits than those reported as node-positive. In cases with infiltrating ductal carcinoma these presented as embolic growth, while those with infiltrating lobular carcinoma, for example, tended to colonize the nodal parenchyma, giving nodal growth. Differentiation between these growth patterns enables pathologists to distinguish between the dangerous embolic type and the less important nodal growth. In conclusion, many of these micrometastases can be detected if the slides reported as node-negative on first reading are re-examined. In those remaining negative, immunohistochemical staining is recommended.

Axilla↗

PubMed1999

Laser conization of cervical intraepithelial neoplasia grade 3: free resection margins indicative of lesion-free survival.

BACKGROUND: Various grades of cervical intraepithelial neoplasia may occur following laser conization for grade 3 lesions. The aim of this study was to assess lesion-free survival after laser conization in cases with/without free resection margins, and to test whether detection of human papillomavirus infection and/or p53 expression in the cone lesion were useful predictors of lesion-free survival. METHODS: In 598 women treated for cervical intraepithelial neoplasia grade 3 the state of the resection margins was recorded and related to the findings on follow-up, up to 15 years post-operatively. Lesion-free survival times were analyzed by the Kaplan-Meier method. The presence/absence of human papillomavirus infection and/or p53 expression in the primary lesion was investigated in every fifth case by in situ hybridization and immunohistochemistry respectively. RESULTS: Lesion-free survival was significantly more common after complete than incomplete excision of cervical intraepithelial neoplasia. In the latter, lesions tended to appear shortly after surgery, indicating the presence of residual disease. The few lesions appearing later were evenly divided between those with and those without complete excision. The results of the human papillomavirus and p53 investigations added no further information. CONCLUSIONS: The presence of cervical intraepithelial neoplasia in the cone margin gives strong indication of potential treatment failure. In its absence laser conization is highly effective in the treatment of cervical intraepithelial neoplasia, and has the advantage of providing a specimen suitable for the necessary histological investigation.

Conization↗

PubMed1998

Prognostic implications of cervical intraepithelial neoplasia in a single cervical smear. an age-matched case-control study of women with negative smear histories.

Our aim was to investigate the prognostic implications of a single cervical smear showing cervical intraepithelial neoplasia (CIN) in a group of women with a previous series of negative smears, and to estimate their risk of developing histologically confirmed CIN 3. A retrospective case-control study was set up. It consisted of 171 cases and 513 age-matched controls, all with at least 3 negative and no positive smears between 1981 and 1988 inclusive. In all cases CIN had been diagnosed on cytology in 1989, while the controls had remained negative. The women were followed up to the end of 1995. The outcome was recorded in terms of regression, progression, persistence or surgical treatment. In women with a single smear showing CIN 1 or 2, the risk of developing histologically proven CIN 3 was 14 and 26 times that in women with negative smears. Negative control smears in the short term did not exclude subsequent progression. Thus women with a single cervical smear indicating CIN 1 had a greatly enhanced risk of producing a lesion that demanded intervention. Such cases should be observed closely with repeat smears over a period of at least 6 years.

Adult↗

PubMed1998

Nodal tumour growth in breast cancer: the time-span of its biological progression.

This series of 1,154 women with unilateral breast carcinoma was treated by modified radical mastectomy with axillary dissection. Histological staging of nodal tumour growth in the axilla distinguished 4 populations in which the numbers of patients presenting for operation over the months of the year differed markedly. The findings are used to develop a hypothesis on nodal tumour growth in which the length of time needed to complete the growth sequence, from the entry of a micrometastasis to exit of tumour cells via the efferent nodal vessels, could be estimated. The results suggest that the time-span may be as much as 3 years, and probably more.

Breast Neoplasms↗

PubMed1998

The size of a micrometastasis in the axilla in breast cancer: a study of nodal tumour-load related to prognosis.

Much has been written on micrometastases to the axilla in breast cancer but there is no consensus as to their size. In this study three levels of nodal tumour-load are defined following measurement of nodal tumour area on histology. The two cut-points described are both of clinical interest. The smallest deposits, up to 0.0001 cm2, include embolic growth on the afferent side of the node, which is, as reported previously, of poor prognosis. In such cases post-operative prognosis approaches that in the "node-positive", here defined as cases with an axillary tumour-load of 0.5 cm2 or more. Between these two groups is a collection of cases, 40% of the total series, with a prognosis similar to the node-negative. It is suggested that the deposits in this intermediate group should be termed micrometastases, the high risk cases with embolic growth reported as such and those with larger deposits as node-positive.

Axilla↗

PubMed1998

Staging nodal growth in breast cancer on a histological basis.

This study describes the axillary tumour-load in 484 women with breast carcinoma with spread to one or more nodes. The aim was to relate tumour-load to nodal histology. The tumour area and that of residual lymphoid tissue was measured from standardised nodal sections. The presence/absence of tumor cells in the efferent vessels (EV) defined their nodal status as EV+ or EV-. The former has a poor prognosis. While the number of EV+ cases increased with the total tumour-load, the number of EV- cases decreased. In the EV+ there was high positive correlation between tumour-load and number of deaths from breast cancer, with a corresponding negative correlation in the EV-. Twice as many patients with EV+ nodes died of breast cancer compared to the EV- group. Investigation of 164 consecutive tumour-bearing nodes showed a similar pattern. Irrespective of EV status the area of residual lymphoid tissue remained constant. Although the lymphoid area was similar the tumour-load was twice as high in the EV+ cases. These findings stress basic biological differences in the growth of breast carcinoma in the nodes. Patients with the smallest micrometastases that are found in the afferent lymphatics of the node and the EV+ patients in which tumour cells are present in the efferent nodal vessels have a poor short-term prognosis. The patients with larger micrometastases in the nodal lymphoid tissue and also EV- patients with the next highest tumour-load are both of low prognostic risk, with the exception of the few EV- with an exceptionally high tumour-load.

Breast Neoplasms↗

PubMed1996

Breast cancer: two micrometastatic variants in the axilla that differ in prognosis.

Measurement of the area of the tumour deposits present in routine sections from the axillary nodes from a series of 1069 breast cancer patients showed that 138 cases had a single micrometastasis (0.2 cm2 or less), while in 29 a similar load was spread over two or more nodes. These 167 cases represent 15% of the patients in the series. Twentyfive of them had died of breast cancer within a mean follow-up of 6 years. They had smaller micrometastases than those surviving (P < 0.0025). Histological examination in the 138 with single micrometastases showed that two variants were present. In one, tumour growth was confined to the capsular lymphatics and/or the subcapsular sinus. In the other, tumour growth was present in the nodal lymphoid tissue, and, on occasion, at the other sites as well. Those with growth in the lymphoid tissue had a better prognosis than those without (P < 0.0035). Prognosis in the former was comparable to that in the node-negative cases, while in those lacking such growth it was similar to that in the node-positive. The presence of these two variants could explain divergent reports in the literature on prognosis in cases with micrometastases. While the mechanisms behind this apparent paradox remain speculative, the observation can be of diagnostic interest in routine surgical pathology.

Axilla↗

PubMed1996

Human papillomavirus infection in progressive and non-progressive cervical intraepithelial neoplasia.

Human papillomavirus (HPV) infection is common in cervical intraepithelial neoplasia (CIN) and is widely held to be responsible for its progression to grade 3. This thesis is examined here. Comparison of the level of HPV changes in 133 lesions that had not progressed to that in those from 197 women with histologically proven CIN 3 failed to reveal significant differences in their level of HPV infection on cytology, histology or in situ hybridization. However, in both these groups, some of the cases that did not show HPV positivity on in situ hybridization with probes reacting with the common HPV types did show evidence of HPV DNA using a general primer-mediated polymerase chain reaction. This may indicate low-copy number infections or non-productive infections. Such reactions were more frequent in the women with progressive lesions, and it is probable that they may also have been at greater risk of cervical infection in general. The present findings suggest that a further factor, a cocarcinogen, may be involved in progression to CIN 3, HPV being a common forerunner, providing a proliferative environment and thus favoring such an event.

Cell Transformation, Neoplastic↗

PubMed1996

Prognostic role of oestrogen and progesterone receptors in patients with breast cancer: relation to age and lymph node status.

AIMS: To consider the prognostic role of oestrogen receptor and progesterone receptor status in relation to the age at surgery, length of follow up and lymph node status. METHODS: The study population comprised 977 patients with histologically confirmed breast carcinoma, with a median follow up of nine years. The actuarial life table method was used to test for survival differences. The Cox proportional hazard model was used to test for interaction effects between each hormone receptor and age, lymph node status and length of follow up. As the analysis involved multiple subgroups, significance was set at the 1% level (p < 0.01). RESULTS: When the patients were subdivided into groups according to lymph node status and age, progesterone and oestrogen receptor status predicted prognosis in middle aged (46-60 years) patients with lymph node positive breast cancer. Their prognostic effect in this subgroup, however, was restricted to the first five years after surgery. Progesterone receptor status was the strongest predictor of outcome. CONCLUSION: The prognostic power of oestrogen and progesterone receptor status varies depending on age, lymph node status and length of follow up after surgery.

Adult↗

PubMed1996

The differences in the cytological histories of women with high- and low-grade cervical intraepithelial neoplasia.

This study concerns 330 women from each of whom we had received a cervical smear showing cervical intraepithelial neoplasia in 1989. They were divided into two groups. One consisted of 197 cases that had progressed to histologically confirmed cervical intraepithelial neoplasia grade 3 between 1989-90, the other of those that had not done so. Their laboratory records (1981-92) were analysed. These showed clear differences in their cervical histories. Those that had progressed rapidly to grade 3 (on histology) were characterized by a short history of abnormal smears. Those that had not progressed over the years tended to have had a series of fluctuating low-grade lesions. On this basis it is suggested that a woman with a negative cervical-smear history, presenting with intraepithelial neoplasia irrespective of grade, should be carefully monitored over the following year to define the nature of the lesion present.

Adult↗

PubMed1996

Micrometastases to the axilla in breast cancer: their size and season of presentation.

In a series of 1,069 breast cancer patients there were no significant differences in the numbers of node-negative or node-positive cases undergoing operation in the two halves of the year. This held also for cases with nodal micrometastases (0.2 cm2 or less). There were two histological types. Their distribution according to season was similar. Using the mean tumour area those presenting in the first half of the year were smaller than the others (p < 0.001), and more cases were under 0.000 cm2 (p < 0.005). In these cases the tumour cells tended to be in the capsular lymphatics and subcapsular sinus. In keeping with their histology, deaths were also more frequent than with those presenting in the second half of the year, in which the micrometastases were larger and had usually infiltrated the nodal lymphoid tissue. Thus the metastatic process in the primary appears to be active in the first part of the year when the smallest of the micrometastases are found entering the nodes. This may be a reflection of the growth form of the primary.

Axilla↗

PubMed1996

Node-positive breast cancer: axillary micrometastases, their incidence and some implications.

In node-positive breast carcinoma, the presence of tumour cells in the efferent vessels (EV) of the axillary nodes (positive EV status) was shown to be of poor prognosis in 1979. Later the presence of nodal micrometastases was also related to survival. This report describes a new subgroup in this system that is of potential therapeutic interest. It consisted of the 40% of the EV-positive cases with micrometastases (< 0.2 cm2) in their nodes, in addition to nodes with macrometastases. In them the difference in prognosis associated with EV status no longer held. Their prognosis did not differ markedly from that in the EV-negative patients. In the absence of such 'additional' micrometastases, the prognostic difference was still highly significant. There was also some indication that the presence of micrometastases consisting of embolic tumour growth alone may be associated with early death in EV-negative cases, in keeping with the prognosis in cases with lone micrometastases.

Axilla↗

PubMed1995

The cervical smear record: its relevance to the subsequent development of cervical neoplasia.

BACKGROUND: Our aim was to investigate the previous smear history in women with cervical intraepithelial neoplasia grade 1-3 or squamous carcinoma and define its relevance to the lesion present in 1989. METHODS: All 850 women with a laboratory record of cervical intraepithelial neoplasia or cervical squamous carcinoma in 1989 were studied. We retrieved their cytological and histological cervical diagnoses for the period 1981 to 1992 from the laboratory files. On this basis we assessed their previous smear history and short term clinical outcome. RESULTS: Half the women had a negative record prior to 1989, irrespective of the grade of their lesion in that year. Cervical intraepithelial neoplasia grade 1 had previously been found in 16%, grade 2 in 10%, and grade 3 in 7%. These levels were not related to the grade present in '89, but as in those with a negative record, were proportional to the number of women examined, and thus reflect the frequency of such lesions in the screened population in general. In all, 310 were treated operatively for cervical intraepithelial neoplasia grade 3 following abnormal findings in 1989. In such cases abnormal findings were also common in '88, although 45% of them still had a negative smear history. The group with no previous record, i.e. unscreened, contained significantly more invasive cases. CONCLUSIONS: In women with cervical intraepithelial neoplasia in 1989, their previous smear history did not indicate the grade of lesion present. The relevance of their previous abnormal slides to that lesion is thus questionable. The findings, however, suggest that progressive lesions may be acute in origin, superimposed in some cases on a history of similar morphological abnormalities.

Adult↗

PubMed1993

Mast cell association with collagen fibres in human breast stroma.

Whirl-like structures consisting of strands and bundles of collagen fibres with a central space are described in human breast stroma. Association between these structures and connective tissue mast cells is demonstrated. Mast cells in these whirls, in contrast to those in loose connective tissue, showed signs of secretory activity. On ultramicroscopy some showed electron-dense bud-like structures at the edge of the cell, and between this and adjacent collagen bundles. In the absence of cytoplasmic cover association was demonstrated between the surface of a mast cell granule and a band of collagen fibres in the stroma. In vitro production of collagen fibres was reported in 1952 on the addition of heparin powder to soluble collagen. The mechanism of that reaction was not further defined. Neither, as yet, is that underlying the present findings. The products of mast cell granules would appear to be common to both. It is suggested that these findings may represent an alternative pathway for collagen deposition in vivo, as in vitro.

Breast↗

PubMed1992

Breast carcinoma: periodicity in presentation of metastatic tumour growth in the axilla.

The clinical value of assessment of tumour load in the axilla in the treatment of breast cancer patients has stood the test of time. Much information is available on its extent and characteristic distribution but, in contrast, little is known of the biological factors that may control the timing of the metastatic phenomenon. There is recent circumstantial evidence that such factors may exist and this prompted the present detailed study of axillary metastases from a series of 437 consecutive cases of breast carcinoma. Evidence of such factors was found here also: the excess of micrometastases in cases coming to operation in the second half of the year was highly significant (P less than 0.001) and is consistent with a synchronized start to the metastatic process. The total metastatic pattern in the material further indicated that the process may show periods of inactivity, i.e. periods when new colonies are not recruited. Mechanisms controlling this periodicity could theoretically be light-mediated, opening up new possibilities in the development of anti-metastatic treatment regimes.

Axilla↗

PubMed1992

Reassessment of tumour-load in the axilla in patients with breast cancer: a preliminary report.

The tumour-load in the axilla of breast cancer patients is classically measured from the number of tumour-bearing nodes present, which is then used to assess prognosis. This preliminary morphometric study on 73 cases of breast carcinoma for which standardized axillary dissection specimens were available shows that the total tumour load, measured from the sum of the tumour area (cm2) in hilar nodal sections, gives a redistribution of the patients; one that may provide better prognostic information in particular in women with a high tumour load. In those with four or more nodes involved the actual number is said to give little prognostic discrimination at 4 years post-operatively, as was demonstrated in this series. In contrast, using data from the same patients, the risk of death by this time increased steadily with increasing tumour area.

Axilla↗

PubMed1992

Koilocytosis in neoplasia of the urinary bladder.

Koilocytosis is commonly regarded as indicative of human papilloma virus infection in the uterine cervix. In 1987 morphologically similar changes were reported in bladder tumours. This is confirmed in the present study, the incidence here being 65%. In addition the incidence of koilocytic change was shown here to increase from non-infiltrative WHO grade I to infiltrative WHO II lesions, and to be more common in bladder lesions in women with cervical koilocytosis. The latter is in keeping with our previous report that the incidence of koilocytosis in the cervix of patients with bladder neoplasia is higher than expected in the general population, adding support to the hypothesis that both lesions may be virus-related.

Adult↗

PubMed1992

Pericytes in human breast stroma and the cells to which they relate.

The function of pericytes, the cells nearest the microvascular endothelium, has long been debated. On the basis of ultrastructural studies it is pointed out that they have specialised features in common with endothelial cells of the lymphatic labyrinth of the human breast. The latter are in continuity with the initial lymphatics. These features, which include points of stromal attachment, allow contraction or relaxation of the cell-processes. The cytoplasmic processes of the pericyte, when relaxed, form areas of contact with the blood vascular endothelium. Subsequent contraction may lead to loss of contact and increase in the area of vascular endothelium available for diffusion. The pericyte is thus equipped to act as a regulatory link between the blood vascular endothelium and that of the fine lymphatic system.

Breast↗