Cancerization of lobules and atypical ductal hyperplasia adjacent to ductal carcinoma in situ of the breast

The splitting of the functions of purchaser and provider in the New Zealand health system in 1993 necessitated the use of explicit contracts between the two parties. This paper examines contracting experiences during the first two years of operation. The study focuses on four services: rest homes, primary care clinics, surgical services, and acute mental health services. The insights of transaction cost economics form the theoretical framework. The objective of this study was to examine whether the transaction costs associated with contracting vary across the four different services, and whether different types of contracts and contractual relationships are emerging as transactors attempt to reduce these costs. Information was collected in a series of 53 interviews with purchasers and providers, together with any relevant documentation. The results suggest that the costs of contracting are indeed greater for some services than for others. Other variables such as the style of negotiations, the type and specificity of contracts and the degree of monitoring also differ across the four services. At this early stage of the reform process, there was little evidence that purchasers and providers were attempting to reduce transaction costs by negotiating more flexible, longer-term, relational contracts. The main benefit from contracting to date has been improved accountability of service providers.     

Evidence of significant apoptosis in poorly differentiated ductal carcinoma in situ of the breast

Following breast-conserving surgery for ductal carcinoma in situ (DCIS), the presence of comedo necrosis reportedly predicts for higher rates of post-operative recurrence. To examine the role of programmed cell death (apoptosis) in the aetiology of the cell death described as comedo necrosis, we studied 58 DCIS samples, using light microscopy, for morphological evidence of apoptotic cell death. The percentage of apoptotic cells (apoptotic index, AI) was compared between DCIS with and without evidence of 'comedo necrosis' and related to the immunohistochemical expression of the anti-apoptosis gene bcl-2, mitotic index (MI), the cellular proliferation antigen Ki67, nuclear grade and oestrogen receptor (ER) status. AI was significantly higher in DCIS samples displaying high-grade comedo necrosis than in low-grade non-comedo samples: median AI = 1.60% (range 0.84-2.89%) and 0.45% (0.1-1.31%) respectively (P < 0.001). Increasing nuclear grade correlated positively with AI (P < 0.001) and negatively with bcl-2 expression (P = 0.003). Bcl-2 correlated negatively with AI (P = 0.019) and strongly with ER immunoreactivity (P < 0.001). Cellular proliferation markers (MI and Ki67 immunostaining) correlated strongly with AI and were higher in comedo lesions and tumours of high nuclear grade (P < 0.001 in all cases). Thus, apoptosis contributes significantly to the cell death described in ER-negative, high-grade DCIS in which a high proliferative rate is associated with a high apoptotic rate. It is likely that dysregulation of proliferation/apoptosis control mechanisms accounts for the more malignant features typical of ER negative comedo DCIS.     

Allelic loss on a chromosome 17 in ductal carcinoma in situ of the breast

Multiple tumor suppressor genes are implicated in the oncogenesis and progression of invasive carcinoma of the breast. To investigate the chronology of genetic changes we studied loss of heterozygosity on chromosome 17 in ductal carcinoma in situ, a preinvasive breast cancer. A microdissection technique was used to separate tumor from normal stromal cells prior to DNA extraction and loss of heterozygosity was assayed mainly using simple sequence repeat polymorphism markers and the polymerase chain reaction. Loss of heterozygosity on 17p was observed in 8 of 28 tumors (29%) when compared with normal control DNA, whereas no loss was seen on 17q, suggesting that at least one locus on 17p is involved early in the development of breast cancer.     

Volume of resection in patients treated with breast conservation for ductal carcinoma in situ

The N-terminal domain (1-318 amino acids) of mouse NFkappaB (p65) has been purified to homogeneity from the soluble fraction of Escherichia coli cells expressing this protein. Its complex with a full-length ikappaB-alpha (MAD3, 1-317 amino acids) molecule was generated by binding the E. coli-derived ikappaB-alpha to the purified NFkappaB and purifying the complex by sequential chromatography. The stoichiometry of NFkappaB to ikappaB in the complex was determined to be 2 to 1 by light scattering and SDS-polyacrylamide gel electrophoresis. The secondary structure of the NFkappaB (p65) determined by Fourier-transform infrared (FTIR) spectroscopy is in good agreement with that of the p50 in the crystal structure of the p50/DNA complex, indicating that no significant structural change in NFkappaB occurs upon binding of DNA. The FTIR spectrum of the NFkappaB/ikappaB complex indicates that its secondary structure is composed of 17% alpha-helix, 39% beta-strand, 18% irregular structures, and 26% beta-turns and loops. By comparing these data to the FTIR data for NFkappaB alone, it is concluded that the ikappaB (MAD3) in the complex contains 35% alpha-helix, 27% beta-strand, 22% irregular structures, and 16% beta-turns and loops. Circular dichroism (CD) analysis of a shorter form of ikappaB (pp40) indicates that it contains at least 20% alpha-helix and that the ikappaB subunit accounts for nearly all of the alpha-helix present in the NFkappaB/ikappaB complex, consistent with the FTIR results. The stabilities of NFkappaB, ikappaB, and their complex against heat-induced denaturation were investigated by following changes in CD signal. The results indicate that the thermal stability of ikappaB is enhanced upon the formation of the NFkappaB/ikappaB complex.     

Mammary ductal carcinoma in situ with microinvasion

BACKGROUND: The natural history of patients with intraductal carcinoma (DCIS) and microinvasion is poorly defined, and the clinical management of these patients, with particular reference to management of the axilla, has been controversial. Previous studies of this lesion have used varied and/or arbitrary criteria for the evaluation of microinvasion. METHODS: Thirty-eight DCIS lesions with microinvasion (n=29) or probable microinvasion (n=9), diagnosed during the period 1980-1996, were retrospectively analyzed after cases not treated with mastectomy and axillary lymph node dissection were excluded. Microinvasion was defined as a single focus of invasive carcinoma < or = 2 mm or up to 3 foci of invasion, each < or =1 mm in greatest dimension. RESULTS: The patients were all females with a mean age of 56.4 years. DCIS was of comedo (n=31) or papillary (n=7) subtype. Microinvasion was often associated with an altered, desmoplastic stroma (55%) or a lymphocytic infiltrate (39%). The foci of microinvasion ranged from 0.25 to 1.75 mm (mean, 0.6 mm), with an aggregate mean size of 1.1 mm (range, 0.25-2.25 mm). Foci of microinvasion, ranging from 1 to 3 (mean, 1.7), were adjacent to DCIS in 95.3% of cases. The extent of DCIS did not correlate with the number of foci of microinvasion. Axillary lymph node dissections yielded a mean of 19.3 lymph nodes (range, 7-38), and all lymph nodes were negative for metastasis. None of 33 patients, followed for a mean of 7.5 years (range, 1.0-14.4 years), developed local recurrence or metastasis. CONCLUSIONS: The cases of microinvasive carcinoma examined in this study, as defined above, were not associated with axillary lymph node metastases and appeared to be associated with an excellent prognosis. Further study is indicated to determine the appropriate management and long term prognosis of patients with this lesion.     

Ductal carcinoma in situ of the breast

PURPOSE: The increasing incidence and biological heterogeneity of ductal carcinoma in situ (DCIS) of the breast have made the management of this entity challenging and controversial. This paper reviews data on the natural history of the disease and results obtained with various management approaches. DATA SOURCES: Computerized MEDLINE search of articles related to DCIS published since 1966. STUDY SELECTION: Randomized trials were given higher value; however, because these were relatively scarce, retrospective studies and data published in abstract form were also included. DATA EXTRACTION: The authors reviewed all sources critically. No formal statistical calculations were made. DATA SYNTHESIS: The incidence of DCIS is increasing, and a greater proportion of diagnoses are being made in asymptomatic patients. No data from randomized trials compare mastectomy and breast-conserving therapy for the treatment of DCIS. A large randomized trial comparing lumpectomy with lumpectomy plus radiotherapy showed lumpectomy plus radiotherapy to be effective for management of this disease. The presence of comedo necrosis and surgical margin status are frequently used as predictors of subsequent recurrence, although this practice is controversial. The risk for in-breast recurrence at 5 years after lumpectomy and radiotherapy is approximately 8%. With more refined molecular analysis, the relation of DCIS to invasive breast cancer will be better defined. CONCLUSIONS: Treatment strategies for DCIS have evolved, and lumpectomy followed by radiotherapy is an appropriate alternative for most patients. The use of lumpectomy alone in selected patients remains controversial.     

Comparative genomic hybridisation of ductal carcinoma in situ of the breast: identification of regions of DNA amplification and deletion in common with invasive breast carcinoma

Comparative genomic hybridisation has been used to map copy number changes in nine cases of ductal carcinoma in situ of the breast obtained from wax-embedded archive material. A wide variety of abnormalities were detected including gain of regions of 1q, 17q, 19q, 20p and 20q and loss on 13q, 14q, 17p, 16q and 22q. Amplification of areas on 10p, 8q and 20q were also observed. Chromosomal alterations were more frequent in higher grade DCIS and closely resemble those previously detected in invasive breast cancer using the same technique. These data provide strong molecular support for the view that DCIS is a precursor lesion of invasive breast carcinoma.     

A practical approach to breast ductal carcinoma in situ and tumors with an extensive intraductal component

Seventy-two patients were admitted in a multicentre trial with the purpose of assessing the clinical efficacy and safety of the hormonal control and tolerance of leuprolide acetate in a once-a-month depot injection formulation for the treatment of disseminated prostate cancer. During a 1-year follow-up, there were ten withdrawals for different reasons. At baseline and at 6 months of treatment the following parameters were evaluated: clinical examination, routine blood analysis, PAP, PSA, LH and testosterone, as well as bone scan. LH and testosterone determinations were repeated at 2, 4, 8, 12, 16, 20 and 24 weeks. Testosterone reached castration levels within the second week and was maintained until the end of the study. In agreement with the NPCP criteria, 65 patients were assessed as: complete response 3%, partial response 40%, disease stabilization 36%, and progression 21%. In summary, a once-a-month injection of leuprolide acetate offers a safe and effective alternative to surgical castration.     

Increases in ductal carcinoma in situ (DCIS) of the breast in relation to mammography: a dilemma

The increased use of screening mammography has resulted in a marked increase in detected cases of ductal carcinoma in situ (DCIS) of the breast since the early 1980s. In 1993, there were an estimated 23,275 newly diagnosed cases of DCIS in the United States, of which 4,676 were in women aged 40-49. DCIS accounted for 14.7% of all newly diagnosed breast cancers in women aged 40-49 in 1993, and perhaps 40% of all mammographically detected breast cancers in this age group are DCIS. Among women aged 40-49, an estimated 1,890 mastectomies and 2,707 lumpectomies (with or without radiation) were performed for DCIS in 1993. There is an urgent need to better understand the relationship of mammographically detected DCIS to invasive and potentially life-threatening breast cancer. Better information about the appropriate treatment of DCIS is also needed to reduce the confusion and uncertainty many women and their physicians currently experience in the face of a DCIS diagnosis. For the present, women considering screening mammography should be told the likelihood of being diagnosed with DCIS and that only some DCIS cases may be clinically significant but almost all will be treated surgically.     

Clinical problems of the breast carcinoma in situ

The results of diminution mammoplasties are reported. From 1972 to 1974, 70 diminution mammoplasties according to Str?mbeck were carried out. Indication for the operation was hypertrophy of the breasts with side effects of morbid value. In 47 patients side effects of the body posture were the leading indication. In 23 patients, psychosocial problems were the indication. Only patients with side effects of morbid value were considered to be sufficiently motivated to tolerate the total stress of the operation and the possible post-operative complications. The technical problems of the operation and the post-operative complications are described. 43 patients were followed up at least one year after the operation. In 36 patients the pre-operative complaints were alleviated by the operation. In 7 patients there was improvement. No patient had continuing pre-operative complaints. The mentally depressed and physically and psychologically in their relationship to their environment handicapped patients became usually more satisfied by the operation. Diminution mammoplasties are recommended for the operative treatment of hypertrophy of the breast with side effects of morbid value.     

Ductal carcinoma in situ: introduction of the concept of ductal intraepithelial neoplasia

The current definition, diagnostic criteria, grading, and approach to assessment of extent of ductal carcinoma in situ (DCIS) are presented. The problem areas, particularly the difficulties in separating low-grade DCIS from atypical intraductal hyperplasia (AIDH), accurate assessment of size and/or extent of DCIS, and their impact on patient management are critically reviewed. On the basis of the route of progression of DCIS, recently confirmed by three-dimensional reconstructed models, an optimal and simple approach to uniform excision, orientation, and processing of biopsy samples is presented. Emphasis is placed on the role of intraductal proliferative lesions (IDH, AIDH, and DCIS) as risk factors of variable magnitude in subsequent development of invasive breast carcinoma. It is proposed that these proliferations should be classified as "mammary intraepithelial neoplasia, ductal type" or as "ductal intraepithelial neoplasia" (DIN); the rational for the application of this classification system is provided. This approach obviates the current separation of AIDH and low-grade DCIS into two very drastically different categories of cancer and non-cancer without interfering with appropriate management of the various lesions. The DIN classification is presented in a simple translational table, along with the current terminology for various lesions.     

Second cancers following in situ carcinoma of the breast

Most reports of midbrain infarction have described clinicoanatomical correlations rather than associations and aetiologies. Thirty nine patients with midbrain infarction (9.4%) are described out of a series of 415 patients with vertebrobasilar ischaemic lesions in the New England Medical Center Posterior Circulation Registry. Patients were categorised according to the rostral-caudal extent of infarction. The "proximal" vertebrobasilar territory includes the medulla and posterior inferior cerebellar artery territory. The "middle" territory includes the pons and anterior inferior cerebellar artery territory. The "distal" territory includes the rostral midbrain, thalami, superior cerebellum, and medial temporal and occipital lobes. Midbrain infarction was accompanied by "proximal" territory infarcts in four patients, and by "middle" territory infarction in 19 patients. Thirteen patients had associated "distal" territory infarcts, three of whom had occipital or temporal lobe infarcts. Only three patients had isolated midbrain infarcts. Cardioembolism (n=11), in situ thrombosis (n=9), large artery to artery embolism (n=7), and intrinsic branch penetrator disease (n=5) were the most common aetiologies. Bilateral infarction and accompanying pontine infarction were associated with the most extensive vertebrobasilar occlusive disease. Midbrain infarction was 10-fold more likely to be accompanied by ischaemia of neighbouring structures than it was to occur in isolation. Recognition of the different patterns of infarction may act as a guide to the underlying aetiology and vascular lesions.     

Tenascin expression in elastotic cuffs of invasive ductal carcinoma of the breast

We studied immunohistochemically one thousand one hundred and thirty-seven cases of primary invasive breast cancers (NST) and adjacent normal mammary glands for tenascin expression, and compared their elastic content to verify if a relationship exists between tenascin expression and elastosis. Periductal, perivascular and stromal elastosis were graded on a scale from 0 to 3 (absent to massive). All carcinomas showed tenascin expression and elastosis with various histological appearances. In the adjacent breast, teanscon was distributed around the normal ducts or with extasia and uctal hyperplasia without atypia. Digestion of the sections with elastase prior to staining resulted in a loss of the specific staining reactions in all areas where elastosis was present. Tenascin staining was observed in the mesenchyme closely surrounding the neoplastic ducts and the cancer cell nests. Stromal tenascin staining appeared stronger in those carcinomas that exhibited marked desmoplastic reactions. The highly differentiated tumours contained more elastosis in their tumour tissue than the poorly differentiated ones, whereas tenascin expression was stronger in poorly differentiated tumours than well differentiated tumours. A strong staining for tenascin was observed in the elastotic cuff. Tenascin staining did not disappear afterwards with elastase. We did not find a statistically significant correlation between tenascin expression, elastosis and prognostic factors such as size of the tumour, lymph node metastasis, tumour necrosis and age. In our study tenascin proved to be an additional element in elastotic areas even though the significance of an association between elastosis and tenascin is still unknown, as is that of elastosis itself.     

Management of ductal carcinoma in situ with nipple discharge. Intraductal spreading of carcinoma is an unfavorable pathologic factor for breast-conserving surgery

BACKGROUND: Surgical management of ductal carcinoma in situ (DCIS) has been a controversial issue in the selection of breast-conserving surgery as a method of treatment. The definition of intraductal spreading of carcinoma becomes an important factor in the decision making process, but little is known about how much intraductal extension influences the spreading of tumor in the whole breast. To define any unfavorable pathologic factors existing in limited surgery for patients with DCIS, the authors investigated histopathologic characteristics using a sequential slicing of tissues. METHODS: Duct-lobular segmentectomy, a limited surgery, was performed on 110 patients with a bloody nipple discharge. Six patients with invasive carcinoma and 17 patients with DCIS subsequently received a total mastectomy. The specimens obtained by segmentectomy and mastectomy were histopathologically examined. Using subserial sections, the authors examined the relationship between intraductal spreading of carcinoma in the segmentectomy specimens and carcinoma residue in the mastectomy specimens. RESULTS: Among 16 mastectomy specimens, the authors found residual DCIS in 6, and atypical ductal hyperplasia in 4. Intraductal spreading of carcinoma was detected in 8 of 16 segmentectomy specimens. Six of eight patients with intraductal spreading had residual DCIS. The other two patients had atypical hyperplasia in breasts. No residual DCIS was detected in the other eight patients without intraductal spreading. Among 12 patients under observation who did not have a mastectomy, invasive carcinoma subsequently developed in 3. Two of three patients had intraductal spreading in segmentectomy specimens. Only 1 of 10 patients without intraductal spreading, however, developed carcinoma. CONCLUSIONS: Intraductal spreading of carcinoma is an unfavorable pathologic factor in breast-conserving surgery for patients with ductal carcinoma in situ with nipple discharge.     

Surgical therapy strategies in carcinoma in situ of the breast

The surgical treatment of carcinoma in situ of the breast depends on the histological type. After detecting a lobular carcinoma in situ (CLIS) either an intensive (aftercare) follow-up is recommended or a bilateral mastectomy. The choice for one of these two very different forms of therapy can be done only after intensive psychological dialog with patient. The reason for the different forms of further treatment is the multicentric and often bilateral occurrence of CLIS and the potential risk of developing an invasive cancer. The therapy of the ductal carcinoma in situ (DCIS), which often spread out in a segment of one breast, is the total excision of the lesion with clear margins. The Van Nuys Prognostic Index depending on the histological results (tumor-diameter, thickness of clear margins, pathocytologic classification) indicates further treatment such as radiotherapy or mastectomy to lower the chance of local recurrence.     

Progression of atypical ductal hyperplasia/carcinoma in situ of the pancreas to invasive adenocarcinoma

Heterochromatin protein 1 (HP1) of Drosophila and its homologs in vertebrates are key components of constitutive heterochromatin. Here we provide cytological evidence for the presence of heterochromatin within a euchromatic chromosome arm by immunolocalization of HP1 to the site of a silenced transgene repeat array. The amount of HP1 associated with arrays in polytene chromosomes is correlated with the array size. Inverted transposons within an array or increased proximity of an array to blocks of naturally occurring heterochromatin may increase transgene silencing without increasing HP1 labeling. Less dense anti-HP1 labeling is found at transposon arrays in which there is no transgene silencing. The results indicate that HP1 targets the chromatin of transposon insertions and binds more densely at a site with repeated sequences susceptible to heterochromatin formation.     

Prediction of local recurrence of ductal carcinoma in situ of the breast using five histological classifications: a comparative study with long follow-up

OBJECTIVE: To identify the independent and differential diagnostic and symptom correlates of suicidal ideation and suicide attempts and determine whether there are gender- and age-specific diagnostic profiles. METHOD: The relationships between suicidal ideation, suicide attempts, and psychiatric disorders were examined among 1,285 randomly selected children and adolescents, aged 9 to 17 years, of whom 42 had attempted suicide and 67 had expressed suicidal ideation only. Youths and their parents were interviewed as part of the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study, using the Diagnostic Interview Schedule for Children Version 2.3 (DISC-2.3). RESULTS: Logistic regression analyses indicated that mood, anxiety, and substance abuse/dependence disorders independently increased the risk of suicide attempts, after controlling for sociodemographic characteristics. There was no significant independent contribution of disruptive disorders to suicide attempts, although its association with suicidal ideation was significant. Substance abuse/dependence independently differentiated suicide attempters from ideators. Noncriterion symptoms that remained significant predictors of suicide risk, after adjusting for psychiatric disorder, included panic attacks and aggressiveness. Perfectionism did not significantly increase suicide risk after adjusting for psychiatric disorder. The association of specific disorders and noncriterion symptoms with suicidality varied as a function of gender and age. CONCLUSION: A monolithic diagnostic risk profile for suicidality, ignoring gender- and age-specific risks, is inadequate. The contribution of substance abuse/dependence in the escalation from suicidal thoughts to suicide attempts is underscored.