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Biomedical subjects

F Hartveit

Publications and source records attributed to F Hartveit.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

Risk of cervical intraepithelial neoplasia in women with glomerulonephritis.

OBJECTIVE: To investigate the occurrence of cervical intraepithelial neoplasia in women with glomerulonephritis and its possible association with immunosuppressive treatment. DESIGN: Retrospective study of cytological or histological specimens from women presenting with glomerulonephritis and a group of case and age matched controls. SETTING: University department of pathology, Norway. PATIENTS: 81 women presenting with glomerulonephritis from 1981 to 1988, from whom gynaecological cytological or histological specimens were available. A group of 162 case and age matched controls. MAIN OUTCOME MEASURES: Age when glomerulonephritis of cervical intraepithelial neoplasia was diagnosed, type and characteristics of kidney lesion, stage of cervical intraepithelial neoplasia and presence of human papillomavirus, use of immunosuppressive treatment. RESULTS: Cervical intraepithelial neoplasia was more common in women with glomerulonephritis than in their controls (16/81 (20%) v 7/162 (4%), p less than 0.001) and was more advanced in those with glomerulonephritis than in the controls (9/81 (11%) of the study group had grade III cervical intraepithelial neoplasia compared with 1/162 (1%) of the controls). The increased occurrence of cervical lesions was independent of the use of immunosuppressive treatment, but the individual lesions tended to be more advanced when it was used (four of the seven cervical lesions in women with glomerulonephritis who had received immunosuppressive treatment were carcinoma in situ). Of the nine cervical lesions tested, seven were virus associated. CONCLUSION: Women with glomerulonephritis should have regular cervical smears, irrespective of their use of immunosuppressive treatment.

Adult

Skip lesions in the axilla in breast cancer, and their association with micrometastases.

The term 'skip lesion', referring to a tumour-bearing node in the axilla in breast cancer, presupposes that nodal colonization usually occurs in sequence with the path of the lymph flow. Skip lesions are thus out of step with the system. The present study of axillary nodes from 73 node-positive patients demonstrates that skip lesions have much in common with lone micrometastases found at any level, and are thus but a variant of the pattern found in early colonization of the axilla. This in turn indicates that in contrast to a progressive build up of tumour growth first at the lower and later at the middle level, early colonization may be a random process. This again stresses the importance of nodal dissection versus biopsy in the management of breast cancer, particularly in view of recent reports on the prognostic significance of micrometastases.

Axilla

Fat emboli in the lymphatic labyrinth in breast stroma.

Fat emboli may be seen in the fine lymphatic system of the human breast. In the present study they are described ultrastructurally in 3 cases in the stroma adjacent to breast carcinomas. While the significance of the finding is obscure at present, it is pointed out that factors leading to the aggregation of chylomicrons can be expected to alter the chemical make-up of the lymph, and this may affect the subsequent behaviour of cancer cells in it.

Biopsy

Periodicity in metastatic tumour growth demonstrated in the human liver at autopsy. Preliminary report.

The present study is based on 1,069 autopsies made up of stomach, breast, renal and colonic cancer. Periodicity is described in the liver weight index (liver weight/body height) at death in patients with liver metastases. The seasonal variation tended to be more marked in females and among older patients, and it differed with tumour type. A period with maximum deaths tended to follow that of maximum liver weight index. A periodic difference previously reported in a small series of malignant melanomas is thus not an isolated phenomenon. This indicates that basic biological pathways concerned with the control of tumour growth may be involved. How the system works remains an open question.

Age Factors

Clinically undiagnosed malignant tumours found at autopsy.

In a series of over 20,000 autopsies carried out over a 25-year period, 700 cancers (11%) were found in patients in whom the diagnosis of cancer had not been considered relevant clinically. In over half of them the unrecognized tumour was considered an incidential finding and thus of no importance to the individual concerned, though of epidemiological concern. As expected from the literature the main organs involved were kidney and prostate, with stomach cancer in third place. In contrast, the unrecognized cancers that caused death were most often from the pancreas or lung, again with the stomach in third place. These patients with stomach or lung cancer were frequently thought to have died of other diseases in the gastrointestinal/respiratory tract, and the disease cited was often present though not the cause of death. These patients tended to be older than those with clinically recognized disease, and had been hospitalized late in the course of their fatal illness, at which time clinical recognition would not have influenced the outcome. Earlier recognition of this type of cancer is thus essential. This cannot be achieved without definition and further analysis of the entities concerned.

Autopsy

Underdiagnosis of carcinoma of the stomach in the elderly: a 25-year autopsy study.

Gastric carcinoma may present atypically in the elderly. Between 1955 and 1979, 571 autopsies on gastric carcinoma cases were carried out at the Gade Institute, Bergen. In 165 of them the diagnosis had not been made clinically. The latter patients were, on average, 10 years older at death than those in whom the diagnosis was made premortem, and their tumours were smaller. In 45 the tumour was considered an incidental autopsy finding, while 58 were diagnosed clinically as advanced cancer of unknown origin. In the remaining 62 cases the cancer was the underlying cause of death. Recognition of an elderly sub-group of patients whose gastric carcinomas presented atypically brings with it an increasing diagnostic challenge in our ageing population.

Aged

Changes in the cancer spectrum at autopsy: 1975-1984.

In an autopsy series of 8571 cases from 1975 to 1984, cancer deaths increased significantly, particularly in those cases over 60 years of age. A similar trend was seen in the mortality statistics from the district. Study of the degree of correlation between the frequency for the different types of cancer and the total deaths from that cancer at autopsy in the population supplies guidelines for use in assessing the relevance of autopsy findings to epidemiological research. It is stressed that without autopsy control monitoring of cancer in a population is incomplete and unreliable. An autopsy frequency of 40 per cent or more for the cancer in question in the population as a whole is required combined with series of 5-600 cases if satisfactory studies are to be initiated. Such conditions are difficult to fulfil for the less common types, but offer a valid approach to the monitoring of those types of cancer that are numerous enough to merit such attention.

Age Factors

Axillary metastasis in breast cancer: when, how, and why?

Axillary metastasis in breast cancer is a time-dependent phenomenon that varies greatly from tumour to tumour. It is discussed in relation to tumour diameter and the growth rate of the tumour cells. It parallels the former but is not directly related to either. A tumour age coefficient (Tac) is presented that demonstrates this lack of interrelationship. Tumour growth in the axillary nodes is progressive and in general mimics the potential tumour load elsewhere in the body. Qualitative rather than quantitative assessment is needed. This can be provided by simple means, using hilar nodal sections from standardised nodal samples. There is, however, as yet no definitive method of predicting the presence/absence of occult distant metastatic spread in either node-negative or node-positive cases. Treatment is thus based on statistical probability, which may or may not be relevant in the individual case.

Axilla

The prognostic role of progesterone receptor status and age in relation to axillary node status in breast cancer patients.

The prognostic role of axillary lymph node status, progesterone receptor (PgR) status, age of the patient at operation, oestrogen receptor (ER) status and tumour diameter was studied in 443 breast cancer patients treated by modified radical mastectomy. Logistic and proportional hazard regression analyses were used to estimate the prognosis from the time of operation up to 60 months. We also estimated the prognosis from 36 to 60 months for those who had survived 36 months (conditional analysis). PgR and age gave significant information in each node class, old age and PgR negativity being disadvantages. PgR status relative to node status was more important for estimating early (24 months) prognosis, while age was of more importance later (60 months). Node status and age were the only variables giving significant information in the conditional analyses. It is thus of importance to consider the time dependency of the prognostic variables when predicting survival in breast cancer patients. No effect was found for ER status or tumour diameter.

Age Factors