Search

Lymphedema is a relatively common, potentially serious and unpleased complication after axillary lymph node dissection (ALND) for breast cancer. It may be associated with functional, esthetic, and psychological problems, thereby affecting the quality-of-life (QOL) of breast cancer survivors. Objective measurements (preferentially by measuring arm volumes or arm circumferences at predetermined sites) are required to identify lymphedema, but also subjective assessment can help to determine the clinical significance of any volume/circumference differences. Lymphedema per se predisposes to the development of other secondary complications, such as infections of the upper limb, psychological sequelae, development of malignant tumors, alterations of the QOL, etc. The risk of lymphedema is associated with the extent of ALND and the addition of axillary radiation therapy. Treatment involves the application of therapeutic measures of the so-called decongestive lymphatic therapy. Prevention is of key importance to avoid lymphedema formation. The application of the sentinel lymph node biopsy in the management of breast cancer has been associated with a reduced incidence of lymphedema formation.

Axillary lymph node dissection (ALND) has a central role in the surgical management of breast cancer; however, it is associated with a potentially significant morbidity. Although post-ALND complications are often minor, in some cases they can persist for a long time following surgery, thereby affecting the quality of life of breast cancer survivors. Seroma formation and altered sensation of the upper limb are the two most common complications following ALND. Lymphedema is the most common potentially severe long-term complication following ALND. Major post-ALND complications (such as injury or thrombosis of the axillary vein and injury to the motor nerves of the axilla) are extremely rare. Meticulous surgical technique and careful selection of patients for postoperative radiation therapy are mandatory to prevent significant morbidity following ALND. The introduction of the technique of sentinel lymph node biopsy in clinical practice has resulted in a significant reduction in the incidence of post-ALND complications.

EUSOMA (European Society of Mastology) is the organisation representing Breast Cancer Specialists in all disciplines, covering all aspects of breast cancer from risk and prevention, through diagnosis and treatment of the primary tumour, follow-up, treatment of recurrent and advanced disease, pathology, reconstruction, psychology and audit. EUSOMA Guidelines have been published on several aspects of breast cancer and are on service provision as well as giving clinical guidance and providing the basis for audit.

The aim of this study is the counting and the immunomorphological and molecular characterization of circulating tumor cells (CTCs) by the isolation by size of epithelial tumor cells (ISET) method in the peripheral blood of patients with breast cancer. An evaluation of the method's ability to reveal the presence of occult carcinoma cells in blood of a patient with breast cancer was performed and the results compared with those obtained by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay for the evaluation of cytokeratin-19 (CK-19) mRNA expression. The feasibility of molecular analysis of CTCs after laser microdissection of filters used in ISET was illustrated, referring to HER-2 amplification. Blood samples drawn from 44 patients with breast cancer were preoperatively analyzed by ISET. From the same samples, total RNA was extracted and submitted to quantitative real-time RT-PCR for the detection of CK-19 mRNA-positive cells using TaqMan technology. HER-2 amplification was measured by real-time RT-PCR on DNA extracted from cells recovered by laser microdissection from 7 selected ISET-positive filters. Of 44 samples, 12 (27%) showed the presence of epithelial cells on the filter (mean +/- SE: 8.5 +/- 2.4 cells per milliliter of blood). A statistically significant agreement (P = .001) was observed between real-time RT-PCR results and those obtained by ISET. With regard to HER-2 amplification, a good correspondence was found between the results obtained from microdissected CTCs and those obtained using DNA extracted from the primary tumor (R = 0.918; P < .01), as well as the immunohistochemistry results. The ISET method allows for the collection of breast carcinoma cells by filtration despite their smaller dimension relative to other carcinoma cell types. The sensitivity and specificity of the method is comparable with those obtained using the quantitative real-time RT-PCR assay for the evaluation of CK-19 mRNA expression. Moreover, the laser microdissection technique allows for the recovery of nucleic acids for further molecular analysis and CTC characterization.

Background: The Pre-Operative "Arimidex" Compared to Tamoxifen (PROACT) study was a randomized, multicenter study comparing anastrozole with tamoxifen as a preoperative treatment of postmenopausal women with large, operable (T2/3, N0-2, M0), or potentially operable (T4b, N0-2, M0) breast cancer. The effect of preoperative endocrine therapy in patients scheduled for mastectomy or with inoperable tumors at baseline was also investigated., Methods: Patients with hormone receptor-positive breast cancer received anastrozole (n = 228) or tamoxifen (n = 223) with or without chemotherapy for 12 weeks before primary surgery., Results: Objective responses for anastrozole and tamoxifen occurred in 39.5% and 35.4% of patients, respectively (ultrasound measurements), and 50.0% and 46.2% of patients, respectively (caliper measurements). In hormonal therapy-only patients (n = 314), feasible surgery at baseline improved after 3 months in 43.0% of patients receiving anastrozole and 30.8% receiving tamoxifen (P = .04). In the intent-to-treat population, improvement in feasible surgery at baseline to actual surgery at 3 months was found to be numerically higher in the anastrozole group compared with the tamoxifen group, although this difference did not reach significance. Drug-related adverse events were reported in 20.2% and 18.1% of patients, respectively, in the anastrozole and tamoxifen groups., Conclusions: Anastrozole is an effective and well-tolerated preoperative therapy, producing clinically beneficial tumor downstaging and reductions in tumor volume. These effects enable more minimal surgical interventions in patients scheduled for mastectomy, and mastectomy in patients with previously inoperable tumors. Anastrozole appears to be at least as effective as tamoxifen in this setting, and more effective than tamoxifen in certain clinically relevant subgroups. Cancer 2006. (c) 2006 American Cancer Society., (Copyright 2006 American Cancer Society)

The aim of this study is to determinate incidence and risk factors for loco regional failure (LRR) (breast, supraclavicular, axillary and internal mammary nodes) and indications for nodal irradiation. From January 1980 to December 2001, 4,185 patients with T1-T2 breast cancer were treated with conservative surgery and whole breast radiotherapy without nodal irradiation at the University of Florence. The median age was 55 years (range 19-86). All patients were followed for a median of eight years (range 3 months to 20 years). Multivariate analysis showed as independent prognostic factors for isolated nodal relapse (NR) the presence of more than three positive lymph nodes (PAN) (p = 0.001), angiolymphatic invasion (p = 0.002) and pT2 (p = 0.02). However, only 4.8% of patients with more than three PAN developed NR as the only site of recurrence. Having one to three PAN was not associated with an increased risk of NR. We believe that it is not necessary to prescribe nodal irradiation to patients with negative or one to three PAN. Regarding patients with more than three PAN, the number of isolated NR is also small to routinely justify a node irradiation.

Within the Italian Breast Screening Network, individual data are collected yearly on about 50% of all screen-detected operated lesions. In 2003 results showed a good overall quality of diagnosis and treatment, and an improving trend over time. Critical issues were identified in the number of cancers diagnosed pre-operatively, which is still below standards, and in the waiting times for surgery. Compliance with recommendations as to not performing frozen section on small lesions and unnecessary axillary dissection for ductal carcinoma in situ still have not reached the target. The sentinel lymph node technique was performed on the axilla in more than 60% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. Preliminary data for 2004 show further progress towards better quality, particularly in pre-operative diagnosis and in the avoidance of frozen section. The detailed results of this survey have been distributed to local and regional screening programmes in order to allow multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volume would provide the best setting for making audit effective in producing quality improvement.

Background: The need to dissect axillary nodes in patients with early breast cancer and clinically negative axilla remains controversial. The aim of the study was to assess the role of axillary radiotherapy (RT) in reducing axillary metastases in patients with early breast cancer who did not receive axillary dissection., Patients and Methods: From 1995 to 1998, 435 patients over 45 years old with breast cancer up to 1.2 cm and no palpable axillary nodes were randomized 214 to breast conservation without axillary treatment and 221 to breast conservation plus axillary RT., Results: After a median follow-up of 63 months, overt axillary metastases were fewer than expected: three cases in the no axillary treatment group (1.5%) and one in the RT group (0.5%). Expected cases were 43 in the no axillary treatment group and 10 in the RT group. Rates of distant metastases and local failures were low, and 5-year disease free survival was 96.0% (95% confidence interval, 94.1%-97.9%) without significant differences between the two arms., Conclusions: This study suggests that occult axillary metastases might never become clinically overt and axillary dissection might be avoided in patients with small carcinomas and a clinically negative axilla. Axillary RT seems to protect the patients from axillary recurrence almost completely.

Tankyrase promotes telomere elongation by interaction with the telomeric protein binding factor TRF1, a negative regulator of telomere extension. We measured tankyrase mRNA by real-time RT-PCR in 66 breast cancers and in paired normal tissues. Results were compared with hTERT mRNA expression. The levels of tankyrase in breast cancers were significantly higher in comparison to normal tissues (P<0.0001) and significantly related to the status of progesterone receptors. No relationship was found between tankyrase and hTERT mRNA expression in breast cancers. According to our results, tankyrase expression appeared up regulated in breast cancers.

Purpose: To evaluate the efficacy of cytology on axillary lymph node ultrasound-guided aspiration biopsy in the reduction of inappropriate surgery, such as the sentinel node (SN) procedure if positive, or axillary dissection if negative., Materials and Methods: Cytology was performed on 159 consecutive cases, on the ultrasonographically most suspicious lymph node. Lymph node histology was used as a reference standard to determine accuracy. Four different scenarios were simulated: routine axillary ultrasonography with cytology of the lymph nodes visible at ultrasonography (A), or of only the lymph nodes suspicious at ultrasonography (B), with ultrasonography limited to clinically negative axillae and cytology of the lymph nodes visible at ultrasonography (C), or only of the lymph nodes suspicious at ultrasonography only (D)., Results: Cytologic sensitivity was 58.6%, specificity 100%. Immediate axillary dissection only in the case of positive cytology would have avoided 6/6 inappropriate axillary dissections and 5/34 (14.7%) inappropriate SN, compared to routine practice (immediate dissection for palpable adenopathy, SN in the remaining cases). Each of the simulated scenarios saved inappropriate surgical procedures (A: 6 dissections, 5 SNs; B: 6 dissections, 3 SNs; C: 13 SNs; D: 11 SNs) at no expense (A and B) or limited expense (C: Euro 348, D: Euro 232 for each inappropriate surgical procedure saved)., Conclusions: Axillary lymph node cytology can save axillary dissections or sentinel node procedures and is recommended as routine practice. Routine axillary ultrasonography, with cytology of sonographically visible lymph nodes, followed by immediate axillary dissection only in case of positive cytology proved to be the best approach in terms of cost-benefit ratio.

The object of this study was to assess quality of care and adherence to treatment guidelines of screen-detected lesions in Italy using a new audit system. Data on screen-detected cases surgically treated in 1997 were collected using a system (QT 2.3) developed within the Italian Group for Planning and Evaluating Mammographic Screening Programmes (GISMa) and the European Breast Cancer Screening Network. Results of 18 performance parameters were considered compared with the reference standards. In 1997, 515 lesions (335 invasive, 60 in situ and 120 benign) in 496 patients were collected from 14 departments in the Central and Northern area of Italy. The 18 indicators were analysed and grouped according to six quality objectives. Some results were good and others were excellent, such as intraoperative identification, breast conservation surgery, adequate axillary procedures and completeness of pathology reports, but most of them failed: waiting times, preoperative diagnosis, employment of frozen section on small lesions and avoiding axillary procedures in ductal carcinoma-in-situ. This work is a first attempt in Italy to evaluate and uniform the criteria adopted for quality control of breast cancer treatment, using a standardised system. Some results are good or excellent, the overall level of compliance with quality indicators is not satisfactory and corrective actions should be undertaken for a number of issues. A continuous monitoring should be performed and appropriate action taken in order to verify the effectiveness of the corrective actions and to provide screen-detected patients with the best quality of care.

The study of the antiproliferative action of somatostatin (ss) is important not only to understand the regulation of neuroendocrine tumours that express receptors (sst), but also non-endocrine tumours which express these receptors. We previously demonstrated the presence of sst2 in a wide panel of cell lines from human neuroblastoma. Although hypotheses have been put forward that treatment with ss or its analogs may be beneficial in oncological patients, this does not appear to be the case in neuroblastoma; patients with high sst2 levels (who are therefore sensitive to ss treatment) have per se a relatively positive outcome. Therefore, adjuvant treatment with ss is not necessary. Viceversa, patients with a poor prognosis are essentially characterized by a low expression of sst2 (and therefore are insensitive to a therapy with ss). In these patients adjuvant treatment with ss might be indicated, but would have little chance of success. Although the majority of neuroendocrine tumours expresses sst2, pancreas and prostate cancer express sst1 but not sst2, and are therefore insensitive to octreotide treatment which binds preferentially to sst2. Tumours like colorectal carcinoma and breast cancer also express sst2 in their more favourable forms. However, the concentration of sst2 in colorectal cancer is similar, if not lower than that in the surrounding normal tissue. Therefore, the probability of successful adjuvant therapy with ss is relatively low. In breast cancer, it is possible that sensitivity to estrogens may have a positive influence on the expression of sst2. This might justify clinical trials with ss in breast cancer.

Background: Axillary lymph node status is the most important pathological determinant of prognosis in early breast cancer. However, axillary lymph node dissection (ALND) performed for pathological assessment is not without costs and morbidity. Recently, radioisotope-guided sentinel node biopsy (SNB) has been proposed as a promising technique for staging breast cancer patients., Aim of the Study: In this study we report our experience (76 patients) in radioguided sentinel node (SN) biopsy in breast cancer. The study was divided into two phases: the first represents our learning curve, necessary to establish our guidelines for its use in clinical practice, while the second phase was aimed at assessing the feasibility of SN localization using preoperative lymphoscintigraphy and intraoperative gamma probe (GP) detection., Methods: All patients underwent lymphoscintigraphy (LS) up to two hours after tracer delivery (99mTc-micro-nanocolloid, four i.d. injections of 200 microCi/200 miccroL around the primary lesion) 24 hours before surgery and GP tracing during surgery. Subsequently ALND was performed for pathological assessment., Results: SNs were identified in 73/76 patients using LS and in 72/76 using GP. In one case the SN was detected by GP alone while in two cases GP was not able to locate the SN although it had been identified by means of LS. Thirty-three of these 73 patients had axillary node involvement. In 31/33 cases the SN was the only positive node. No positive nodes were found in the remaining 40 ALNDs where SNs were identified. Thus, according to our experience 40/73 ALNDs could have been avoided. SNB seems to be a very interesting technique but further experience in lymph node radioisotope tracing is needed.

The European Society of Surgical Oncology is actively involved in the promotion of a high standard of surgical oncology throughout Europe. Such an ambition involves recognition of Centres of Excellence in the management of cancer patients throughout Europe. These centres have a multi-disciplinary system involved in the total care of patients with cancer and are concerned with the delivery of care to the highest available standards. It is accepted that not all patients with cancer can, nor should, necessarily be treated in such highly specialized centres. Yet all cancer patients should be guaranteed a high standard of care. High surgical standards can be ensured if surgeons treating cancer are trained in specialist centres and, when in independent practice, follow established guidelines or protocols of treatment. In common with many national surgical oncology societies, the European Society of Surgical Oncology is in the process of establishing good practice guidelines in the treatment of solid tumours. This document on the management of symptomatic breast cancer is the first of a series of guidelines to be proposed by ESSO. It draws heavily on excellent documents already in existence from the British Association of Surgical Oncology and from the Danish Breast Cancer Co-Operative Group. It is hoped that this document will be sufficiently clear and purposeful to be of help to the individual surgeon and yet sufficiently flexible to allow it to be adopted in the different medical systems throughout Europe.

The European Guidelines developed for mammography screening have contributed to the general discussion on quality assurance and the important tasks of the health professionals dealing with breast cancer screening. The cooperation of each medical discipline is of utmost importance in order to achieve optimal results and eventually a mortality reduction. The following guidelines are based on the British NHS quality assurance guidelines for surgeons in breast cancer screening and modified to meet the different needs in the European Countries. The term "surgeon" denotes a medical doctor trained and involved in the surgical treatment of breast diseases. The members of the working group who participated in order to adapt these guidelines are listed above. We hope that this document will contribute towards a more comprehensive approach of breast cancer screening-detected lesions throughout Europe.

Aims and Background: The association of p53 protein accumulation and prognosis in node-negative breast cancer patients has been alternately demonstrated and denied in literature reports, and opinions on the use of p53 expression as an indicator of high risk of recurrence and as a guide for adjuvant therapy are controversial., Study Design: The association of p53 protein accumulation with prognosis was retrospectively evaluated in a series of 221 node-negative breast cancer patients treated with surgery alone and followed up for a minimum of 10 years. p53 accumulation was determined by immunohistochemistry on archive material, and classified into four grades of increasing immunostaining., Results: No association was observed between p53 and age or pT category, whereas a significant association with nuclear grade was found (P = 0.0014). Univariate and multivariate analysis of 10-yr disease-free and overall survival showed a significant and independent prognostic association for tumor size (pT category) and nuclear grading but not for p53 expression, whatever grade grouping was used., Conclusions: We did not find any evidence supporting the use of p53 immunostaining in current practice as an independent prognostic indicator or as a discriminant factor for adjuvant treatment of node-negative breast cancer patients.

The accurate locoregional staging of rectal cancer is important in choosing and planning therapy. The diagnostic contribution of endorectal ultrasonography and of Computed Tomography is well known because both methods have been widely used in the last ten years. More recently, Magnetic Resonance Imaging (MRI) has been introduced in the preoperative staging of rectal cancer: most interestingly, in the last three years endorectal surface coils have become available as a clinical device. February through November, 1994, twenty patients affected with rectal carcinoma were examined with endorectal MRI. In order to assess their accuracy, MR staging results were compared with pathologic findings. MRI was performed with an 0.5 T system equipped with an endorectal surface coil. In all cases T2-weighted turbo spin-echo sequences were performed on axial and sagittal or coronal planes. Rectal wall layers were reliably demonstrated in all patients. The comparison with pathologic findings showed 78.9% MR accuracy in assessing tumor infiltration depth. In addition, the study of perirectal lymph nodes showed 83.2% MR sensitivity and 53.8% MR specificity. The high resolution images obtained using endorectal surface coils and the well-known panoramic capabilities of this method reveal MR potentials in rectal carcinoma staging.

Frozen section (FS) diagnosis was routinely performed in a large series of nonpalpable breast lesions from 1977 through 1991. The original FS diagnoses of 672 patients were classified in four categories (1 = benign lesion, 2 = in situ carcinoma, 3 = invasive carcinoma, 4 = deferred diagnosis) and compared with the diagnoses obtained at review of the permanent paraffin sections to estimate the accuracy of FS. A review of the mammographic pattern of the lesion was also performed. Frozen section diagnostic conclusion was deferred to permanent paraffin sections in only 22 cases (3.3%). Benign or malignant (grouping in situ and invasive carcinomas) FS diagnoses were accurate in 623 of 650 cases (95.8%). Overall, the prevalence of malignant lesions was 44.8% with a benign/malignant ratio of 1.2. The diagnosis was modified on the basis of permanent sections in 27 cases (4.2%) with three false positives and 24 false negatives. Sensitivity and specificity of FS diagnoses were 91.7 and 99.2%, respectively. When the comparison between FS and histologic diagnoses was analyzed according to the mammographic pattern, sensitivity among patients with microcalcifications as the only alteration was lower (88.8%) than among patients with opacities (94.9%). On the basis of these results, FS is to be considered a feasible and reliable diagnostic procedure in nonpalpable breast lesions, particularly in cases excised because of a mammographic opacity that is identifiable on gross examination of the surgical specimen.

Between 1986 and 1995, 965 patients with T1 breast cancer were treated with wide excision (796 pts) or mastectomy (138 pts). Axillary dissection was performed in 934 patients. Nodal positivity was 8.7% for T1a, 15.6% for T1b and 37.7% for T1c. 68.5% of cases had one to three positive nodes, 18.3% four to ten and 13% more than ten nodes. No differences were observed in the frequency of lymph nodes involved according to the age of patients, menopausal status, pattern at mammography, histology and receptor status. Favourable histology (tubular, cribriform, papillary, colloid) shows a significant difference when compared with all the others histotypes. On the basis of data collected it is impossible to anticipate the axillary status and avoid axillary dissection.

In breast cancer the study of prognostic factors has been well developed during last years and many biologic and biochemical parameters have been analyzed. Cell kinetics parameters demonstrated the capability to select patients with different risk of evolution of the neoplasia and in some cases treatment protocols are established by means of proliferation rate. The present study deals with the determination of Thymidine Labelling Index in breast tumors mostly T1-T2 with negative lymph nodes. Results demonstrated that the proliferative activity is higher in younger patients, in T2 cancers compared to T1, and in ductal infiltrating forms compared to the other more frequent histotypes. A significant correlation has been observed between TLI and nuclear grade. The preliminary analysis of the prognostic value of TLI has been two performed using an experimental cut off that is able to discriminate groups of patients with overall survival rate of 67% and 88%, depending on the different proliferative activity of the tumor.

A series of 59 phyllodes tumors of the breast was retrospectively reviewed (average follow-up = 3.9 years). Clinical features (age, size of tumor) and diagnostic tests (palpation, mammography, sonography and cytology) were found to be inaccurate in predicting benign (n = 22), borderline (n = 12) or malignant (n = 25) histological type. Limited surgery was associated with a relatively high proportion of local recurrence (enucleation/enucleoresection = 3/5, wide resection = 12/30) compared with mastectomy (2/24). No significant association was observed between the probability of local recurrence and patient's age, histological type or lesion size. Although the study confirms that limited surgery may cure phyllodes tumor, careful follow-up of all patients is needed, since no reliable risk factors for recurrence are available. In malignant cases, axillary node involvement was nil and distant metastases were infrequently observed (3/25). Axillary dissection and search for asymptomatic metastases is not recommended.

The authors report on a retrospective consecutive multicentric series of 60 cases with histologic evidence of lobular carcinoma in situ (LCIS), followed for an average of 5.3 years. In the course of the follow-up, ipsilateral LCIS or infiltrating carcinoma occurred in 3 or 5 cases, respectively. Two LCIS reoccurrences and all ipsilateral infiltrating carcinomas were observed in 37 patients treated by limited surgery. Contralateral synchronous or metachronous carcinoma was observed in 3 or 2 cases, respectively (intraductal = 3, infiltrating = 2). Three patients died of breast cancer (2 with ipsilateral, 1 with ipsilateral and contralateral infiltrating carcinoma). The study confirms the higher risk of ipsilateral and contralateral cancer in LCIS patients and warns about the possible hazards of limited surgery in these cases.

A multicenter retrospective series of 70 breast sarcomas (malignant cystosarcoma phyllodes (25), osteosarcoma (12), liposarcoma (10), stromal sarcoma (8), angiosarcoma (7), mixed types sarcoma (4), malignant histiocytoma (3), leiomyosarcoma (1)) was reviewed. The average follow-up was 5.9 years. Diagnostic tests (palpation, mammography, sonography and cytology) were poorly sensitive, and a large proportion of cases, appearing as regular, sharp bordered, rounded masses were diagnosed as benign fibroadenomas. Surgery (limited (29), mastectomy (41)) was the treatment of choice. Axillary nodes were rarely involved (2 of 31) at pathologic staging. No significant predictors of local recurrences (12 cases) were observed although recurrences were more frequent in larger lesions (0-20 mm = 1.1%, 21-50 mm = 1.7%, > 50 mm = 6.1% women-year) and in cases treated with limited surgery (limited surgery 4.6%, mastectomy 2.0% women-year). Distant metastases (16 cases) were less frequent in malignant cystosarcoma phyllodes or liposarcoma patients, but no other significant predictors of distant metastases were evidenced. Five-year disease-free or overall survival was 50% or 66%, respectively. The study confirms that breast sarcomas are rare, difficult to diagnose, but can be cured by surgical treatment in a considerable proportion of cases.

CA 15-3 and MCA assays were tested in 103 operable patients (preoperative determination) and 100 patients with advanced breast cancer. Normal CA 15-3 and MCA values were determined in a series of 68 healthy women. The negative/positive cut-off was set at 28.8 U/ml and 15.5 U/ml respectively for CA 15-3 and MCA (mean value + 2SD). Results were analyzed in the two groups and with respect to T and N pathological categories in the preoperative series. In pT1 (59 pts), pT2 (30 pts), pT3 + pT4 (14 pts), pNO (58 pts), pN1 (45 pts) and overall preoperative series CA 15-3 and MCA sensitivities were respectively 25%, 40%, 57%, 22%, 42%, 30% and 27%, 30%, 35%, 21%, 33%, 26%. In the patients affected by widespread disease, sensitivity was 92% and 80% for CA 15-3 and MCA. Results were significantly different among normal, preoperative and advanced patients (P less than 0.05). Our results suggest that CA 15-3 and MCA levels are correlated with the tumor mass. Nevertheless, the low sensitivity in pT1 and pNO cases indicates that these two assays have no role in the diagnosis of early breast cancer. In the advanced patients, too, the results can be questioned: in the present study, in fact, recurrent cases were characterized by gross disease with multiple site involvement and cannot be considered as an example of early diagnosis of breast cancer recurrence.

2740 consecutive breast cancers undergoing physical examination were reviewed. Ninety-two subclinical cancers detected at mammography were excluded from further evaluation and the study focused on palpable false benign cancers. The sensitivity of physical examination varied according to T category (TIS = 0.48, T1 = 0.70, T2 = 0.90, T3 = 0.89, T4 = 0.93), age (20-29 = 0.77, 30-39 = 0.58, 40-49 = 0.75, 50-59 = 0.84, 60-69 = 0.90, greater than 69 = 0.94) and operator (range 0.69-0.89), a significant difference being recorded in favor of more expert operators. Multivariate analysis (Cox) showed that T category, patient's age and operator experience are independent determinants of sensitivity. This study confirms that physical examination is not very sensitive, particularly for small tumors and in younger women and should always be performed by expert operators.

A multicenter series of 350 intraductal breast cancers (DCIS) is reported. Mammography was the most sensitive test but suspicion arose only at palpation in 13% of cases whereas in 10% of cases biopsy was recommended for a benign lesion and DCIS was an unexpected finding. Mammography, physical examination and cytology must be combined to achieve optimal sensitivity. Systematic biopsy of apparently benign masses would increase DCIS detection rates but the cost-effectiveness of such a policy is questionable. A trend of conservative surgery was evident over time (from 1968-79, 28%; 1985-1989, 50%) but breast irradiation followed only in one fourth of the cases. The local recurrence rate was significantly higher in cases of limited surgery (with or without irradiation) with respect to mastectomy (1.2 vs 0.2 x 100 patient-years at risk). Most recurrences (7 of 8) in the conserved breast were infiltrating, but no recurrence was seen in subclinical DCIS cases. Three patients died of breast cancer after local recurrence in the conserved breast (2 cases) or mastectomy scar (1 case). Eligibility for conservative surgery of DCIS needs to be carefully discussed to avoid under-treatment. Contralateral breast cancer was recorded in 44 cases and the incidence of further metachronous cancer to the other breast was ten times higher than expected in normal breasts. Four patients died of contralateral breast cancer, free of ipsilateral recurrence. A careful follow-up of the contralateral breast in DCIS cases looks as important as surveillance of the conserved breast.

Estrogen receptors (ER), progesterone receptors (PR) and alkaline phosphatases (AP) were measured in 150 tumors from patients who underwent mastectomy for primary breast cancer. The percentage of ER positive samples was inversely related to the AP activity ranging from 88.9% in low activity samples (less than 30 U/mg prot.) down to 30.6% in the high activity ones (greater than 400 U/mg prot.). When considering only ER positive samples, the ER content was inversely related to the AP activity. This could not be demonstrated for PR. Therefore, the authors suggest the hypothesis that in human breast cancer, the AP may play a role in the dephosphorylation of the ER molecule and in the consequent modulation of its binding capability.

We report on 156 consecutive cases of in situ ductal carcinoma (DCIS) of the breast observed from 1968 to 1988. The relative frequency of DCIS was much higher in screened, with respect to self-referred, women and a significant association of DCIS with younger age was observed. The combined use of mammography and physical examination identified 138 of 156 total DCIS cases as suspicious. Mammography, physical examination or cytology (of nipple discharge or needle aspirate) were the only tests to provide suspicious evidence in 35, 22 and four cases respectively. DCIS was a relatively unexpected surgical finding in 13 apparently benign cases. Different surgical options were recorded in the study period but a temporal trend in favour of conservative surgery was evident. Subsequent ipsilateral or contralateral breast cancer was recorded in seven and six cases respectively. Death from breast cancer occurred in five cases, all of whom had contralateral or subsequent ipsilateral infiltrating cancer. This figure confirms the high curability of DCIS if local control is achieved.

This study was undertaken to compare the changes in physiologic variables caused by the use of two different types of pump-assisted veno-venous bypass during experimental liver transplantation. The experiments, performed on female pigs weighing 30 +/- 2 kg, were divided into two groups depending on the bypass used. During the anhepatic phase a pump-assisted portal-jugular (PJ) bypass was used in Group 1 (n = 8) at a flow rate of 15 ml kg-1-min-1, while a pump-assisted caval-portal-jugular (CPJ) bypass was used in Group 2 (n = 8) at a flow rate of 20 ml kg-1-min-1. Intraoperative haemodynamics, pulmonary gas exchange, haematological and serum biochemical parameters were evaluated. Postoperative animal survival rate and complications associated with the bypass used were evaluated. Mean pulmonary artery pressure (Ppa) and pulmonary vascular resistance (Pvr) showed significantly different behaviour in the two groups, whereas the remaining parameters all showed the same trend. Thus an earlier and more substantial increase in Ppa and Pvr values was found in Group 1 when compared to Group 2 during the anhepatic phase. The different behaviour shown by Group 1 may depend on the release of circulating vasoactive substances generated following pelvic venous congestion caused by the temporary clamping of the inferior vena cava. In conclusion, this study indicates that the pump-assisted CPJ bypass is more suitable than the pump-assisted PJ bypass. Furthermore, in order to obtain better results it should be used routinely in porcine liver transplantation.

A consecutive series of 185 instances of histologically confirmed nonpalpable infiltrating carcinoma of the breast is presented. Histologic nodal involvement was found in 12 per cent and was dependent on the size of the tumor. Conservative surgical treatment was the predominant method used during the study period. The ten year over-all survival was studied and compared with that of 4,217 instances of palpable carcinoma of the breast observed during the same period. The ten year survival rates were, by far, better for nonpalpable (94 per cent) than for palpable carcinomas (65 per cent). A better prognosis for nonpalpable carcinomas was confirmed also by multivariate analysis (Cox) with adjustment for potential confounders, such as age, stage or nodal involvement. The possible confounding effect of over diagnosis and length or lead time bias is discussed. Although this difference in survival might be partially explained by the aforementioned confounders, the chance of increasing life expectancy and conservative surgical treatment encourages preclinical detection of carcinoma of the breast.

Many biological substances are commonly used as markers for malignant neoplasms, but no single marker with high specificity and sensitivity has been found for cancer to date. In this study we evaluated simultaneously the serum levels of five biomarkers of malignancy: phosphohexose-isomerase (PHI), creatine kinase isoenzyme BB (CK-BB), alpha 1-acid glycoprotein (AAG), beta 2-microglobulin (BMG), and ferritin. In 89 female patients with breast lesions, we identified 30 benign lesions, 32 primary breast cancers, and 27 metastatic breast cancers (pulmonary and/or bone metastases). Each marker was assayed individually and in a combination and was compared with other markers. The results revealed that in benign lesions only 7% had PHI values higher than our cut-off limit value, while 3% had elevated values of AAG, BMG, and ferritin. In primary breast cancer we discovered pathological values of CK-BB and AAG in 71%, of PHI in 69%, of BMG in 50%, and of ferritin in 47%. Metastatic disease was associated with elevated values in 88% of CK-BB, in 70% of PHI and AAG, and in only 55% of BMG and ferritin. Combined pathological values for primary and metastatic breast cancer were 79% for CK-BB, 71% for AAG, 70% for PHI, and only 55% for BMG and ferritin. These data were assessed by the Student t test, which revealed for each marker a significant capacity (P less than 0.01) to discriminate between benign lesions and neoplastic diseases. The same capacity to distinguish between primary and metastatic cancer was obtained by the simultaneous use of three markers (CK-BB, PHI, and AAG).(ABSTRACT TRUNCATED AT 250 WORDS)

The immunoradiometric assay "CA 15-3", recently developed to measure a breast tumor-associated antigen, gave a mean serum value of 13.8 U/ml (S.D. 6.2) for this antigen in 156 non-cancer controls (36 biopsies for a benign breast lesion and 120 healthy controls). Setting a cut-off value of 30 U/ml (specificity 99.3%), only 3 out of 58 primary breast cancer cases were positive. In metastatic breast cancer, 11 out of 33 cases with limited recurrence (33.3%) and 36 out of 56 cases with extensive recurrence (64.3%) gave abnormal values in this assay, above the cut-off point, with an overall sensitivity of 52.8%; the difference between the sensitivity values in the two groups of recurrent cases was statistically significant (P less than 0.01). According to the findings of the present study, CA 15-3 has no role in the detection of primary breast cancer, but its usefulness in disease monitoring can be hypothesized, as circulating levels of the antigen seem to be dependent on the tumor mass.

The diagnostic role of physical examination (PE) is evaluated in 1450 cases of breast cancer detected in 34,677 women controlled at the Centro per lo Studio e la Prevenzione Oncologica in the period 1974-1981. In 47 cancer cases, PE findings were normal since the neoplasm was not clinically palpable because of its size and site, and in another 185 cases the clinical diagnosis was benignancy without evidence of suspect signs. Therefore, the overall sensitivity of PE was 84%. PE errors did not involve a therapeutic delay for the patient in 75% of cases in which a biopsy was recommended for clinical benignancy or for suspicion on the basis of other diagnostic methods. The present study confirms that PE has a good diagnostic sensitivity when the examined population is represented by self-referred women, who for the most part are symptomatic, whereas it cannot be considered as the only diagnostic test for early diagnosis in mass screening, since in asymptomatic women a large number of cancers are not clinically palpable. Moreover, PE shows lower sensitivity for small lesions and in younger women. Extensive use of fine needle aspiration cytology and other diagnostic methods in association with PE is therefore recommended to reduce the possibility of errors.

The authors report on 767 consecutive primary Stage I-II breast cancer cases followed-up from 3 to 8 years. The estrogen receptor (ER) content was determined in all cases and did not influence the treatment choice. A correlation was attempted between ER and menstrual or pathological nodal status (N) or the 5-year disease-free survival (DFS). ER was correlated with menopausal status ER+ cases being more frequent in postmenopausal patients, whereas no correlation was observed between ER and nodal status. In absence of nodal involvement (N-) the prognosis was not influenced by the ER status. A significantly better DFS was evident for ER+ respect to ER- patients in the N+ series but such a correlation is questionable as the adjuvant treatment (hormone or chemotherapy) given to such patients may have influenced the DFS according to the ER status. According to the present study, ER determination should not be used as a discriminant in the performance of adjuvant postoperative treatment based on a prognostic judgment.

We report on the possible diagnostic and prognostic role of circulating immune complexes (CIC) determination in breast cancer. A sensitivity of 87% and a specificity of 90% were observed in a case-control study of 15 cancers and 25 noncancer healthy controls. A direct correlation of CIC level to the presence and probably to the entity of the tumor mass was assessed by comparing preoperative to postoperative CIC determinations in cancer cases: CIC levels were significantly lower after tumor removal. These preliminary results suggest further studies on the use of CIC determination in the follow-up of breast cancer for the early diagnosis of recurrent disease.

The authors report on 1,017 consecutive breast cancer cases without symptomatic metastases staged by means of chest X-ray (CXR), skeletal survey (BXR) and bone scintigraphy (BS). Occult metastases (DM) detection rate was 0.88%: 0.29% for lung and 0.59% for bone DM. The detection rate was correlated with clinical stage: 0.36% for stage I, 0.20% for stage II, 0.26% for stages I and II, and 2.77% for stage III cases. The sensitivity based on DM cases prevalent or surfacing within 6 months of follow-up was 0.30 for CXR, 0.22 for BXR and 0.55 for BS; specificity was 0.99, 0.98 and 0.90, respectively. The study confirms the possibility of early detection of DM with preoperative staging, but the extremely low detection rates in stage I and II cancers do not advise such a routine procedure. The higher detection rate of DM may suggest adoption of the routine staging procedure in stage III cancers. In these cases, although no evidence is available of a favorable prognostic impact of early detection and treatment of DM, an unnecessary mastectomy could be avoided in about 3% of cases in the presence of DM detected by the staging procedure.

The authors report on 283 primary, non-metastatic, breast cancer cases consecutively referred after surgery and followed-up from a minimum of 10 months to a maximum of 3.5 years. All cases were studied according to the presence of estrogen receptors (ER). ER presence was correlated with age and menstrual status, with ER+ cases more frequent in older patients. No correlation was found between ER and nodal status. Prognosis was evaluated in terms of disease-free survival at 2 years (actuarial method). No correlation between ER and survival was evident for N- cases, whereas a better prognosis was recorded for ER+N+ patients compared to ER-N+, although the difference was not statistically significant. The observed results are compared with recent literature data and agree with other recent reports, which did not confirm the previously undiscussed statement regarding the prognostic role of ER determination. According to these studies and to the present study, the prognostic role of ER determination seems at least questionable and particularly the postoperative adjuvant treatment of ER-N- cases should be reconsidered.

Thirty-seven (4.1%) cases of nodal metastases skipping the first level are reported in a consecutive series of 912 breast cancer axillary dissections including 392 N+ cases. First level nodes examination is sufficiently accurate in assessing the quality of nodal status (negative or positive) but not the extent of nodal involvement (number of involved nodes).

The authors report on a consecutive series of 1979 TIS-T1A-T2A-T3A breast cancer cases surgically treated from 1979 to 1985. The study investigates the impact of recent reports on conservative surgery and of a national treatment protocol for breast cancer, encouraging the use of modified radical mastectomy (MRM) and quadrantectomy, axillary dissection and breast irradiation (QUART) as alternatives to Halsted's radical mastectomy (RM). RM frequency dropped from 52% to 8% in TIS-T1A and from 82% to 20% in T2A-T3A cases in the study period, in favor of MRM and of QUART, which increased from 10% to 54% in TIS-T1A cases. Although surgical choices differ widely according to individual surgeons, a definite trend towards more conservative surgery is evident, which demonstrates how the national treatment protocol has affected current surgical practice.

The results of 56 consecutive orthotopic liver transplants in the pig were reviewed to determine the incidence of primary biliary tract complications. There were 8 biliary tract complications in 56 grafts (14.2%) directly responsible for death. End-to-end choledochocholedochostomy (ee-CC) was the most frequently used technique (40 cases) with 4 technical failures (10.0%). Choledochojejunostomy with a Roux-en-Y jejunal loop (RYCJ) was used in 9 cases with 2 technical failures (22.2%). Side-to-side choledochocholedochostomy (ss-CC) was used in 7 cases with 2 technical failures (28.5%). Biliary leak and stenosis were the most common complications. End-to-end choledochocholedocostomy appears to be the most suitable and easy biliary reconstruction in the pig but possible gross disparity in the sizes of the donor and recipient ducts may represent and adverse factor.