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Abstract: Background: Axillary lymph node dissection (ALND) in early-breast cancer patients with positive sentinel node (SLN+) may not always be necessary. Aims: To predict the finding of ≥1 metastatic axillary node in addition to SLN+(s); to discriminate between patients who would or not benefit from ALND. Methods: Records of 397 consecutive patients with 1-2 SLN+s receiving ALND were reviewed. Clinico-pathological features were used in univariate and multivariate analyses to develop a logistic regression model predictive of the risk of ≥1 additional axillary node involved. The discrimination power of the model was quantified by the area under the receiver operating characteristic curve (AUC) and validated using an independent set of 83 patients. Results: In univariate analyses, the risk of ≥1 additional node involved was correlated with tumor size, grade, HER-2 and Ki-67 over-expression, number of SLN+s. All factors, but Ki-67, retained in multivariate regressions were used to generate a predictive model with good discriminating power on both the training and the validation sets (AUC 0.73 and 0.75, respectively). Three patient groups were defined based on their risk to present additional axillary burden. Conclusions: The model identifies SLN+-patients at low risk (≤15%) who could reasonably be spared ALND and those at high risk (>75%) who should receive ALND. For patients at intermediate risk, ALND appropriateness could be individually evaluated based on other clinico-pathological parameters. [Copyright &y& Elsevier]

Abstract: Background: Feasibility and accuracy of sentinel node biopsy (SLNB) after the delivery of neo-adjuvant chemotherapy (NAC) is controversial. We here report our experience in NAC-treated patients with locally advanced breast cancer and clinically positive axillary nodes, and compare it with the results from our previous randomized trial assessing SLNB in early-stage breast cancer patients. Patients and methods: Sixty-four consecutive patients with large infiltrating tumor and clinically positive axillary nodes received NAC and subsequent lymphatic mapping, SLNB and complete axillary lymph node dissection (ALND). The status of the sentinel lymph node (SLN) was compared to that of the axilla. Results: At least one SLN was identified in 60 of the 64 patients (93.8%). Among those 60 patients, 37 (61.7%) had one or more positive SLN(s) and 23 (38.3%) did not. Two of the patients with negative SLN(s) presented metastases in other non-sentinel nodes. SLNB thus had a false-negative rate, a negative predictive value and an overall accuracy of 5.1%, 91.3% and 96.7%, respectively. All these values were similar to those we reported for SLNB in the settings of early-stage breast cancer. Conclusion: SLNB after NAC is safe and feasible in patients with locally advanced breast cancer and clinically positive nodes, and accurately predicts the status of the axilla. [Copyright &y& Elsevier]

Abstract: Aim: To investigate whether omitting intra-operative staging of the sentinel lymph node (SLN) in T1-N0 breast-cancer patients is feasible and convenient because it could allow a more efficient management of human and logistic resources without leading to an unacceptable increase in the rate of delayed axillary lymph node dissection (ALND). Methods: According to the experimental procedure, T1a–T1b-patients were to not receive any intra-operative SLN evaluation on frozen sections (FS). In all T1c-patients, the SLN was macroscopically examined; if the node appeared clearly free of disease, no further intra-operative assessment was performed; if the node was clearly metastatic or presented a dubious aspect, the pathologist proceeded with analysis on FS. T2-patients, enrolled in the study as reference group, were treated according to the institutional standard procedure; they all received SLN staging on FS. Results: The study included 395 T1-N0-patients. Among the 118 T1a–T1b-patients whose SLN was not analyzed at surgery, 12 (10.2%) were recalled for ALND. In the group of 258 T1c-patients, 112 received SLN analysis on FS and 146 did not. An SLN falsely negative either at macroscopic or FS examination was found in 33 (12.8%) cases. Overall, the rate of recall for ALND was 11.6% as compared to 8.4% in T2-patients. Using the experimental protocol, the institution reached a 9.6% cost saving, as compared to the standard procedure. Conclusions: Omission of SLN intra-operative staging in T1-N0-patients is rather safe. It provides the institution with both management and economical advantages. [Copyright &y& Elsevier]

Abstract: Aim: To identify by means of clinical and histopathological features a subset of breast cancer patients with sentinel lymph-node (sN) micrometastases and metastatic disease confined only to the sN in order to spare them an unnecessary axillary lymph node dissection (ALND). Materials and methods: From January 1998 to December 2004, 116 patients with sN micrometastases underwent standard ALND for early-stage (T1–2 N0 M0) invasive breast cancer; clinical and histopathologic parameters were prospectively collected and evaluated by means of univariate and logistic regression analysis in order to identify which patients with sN micrometastases were free of metastasis in axillary non-sN. Results: Sixteen of 116 patients with sN micrometastases had tumour involvement of non-sN, with six and 10 patients having non-sN micrometastases and macrometastases, respectively. None of 19 patients with primary tumour measuring ≤10mm had tumour-positive non-sN; moreover, none of 15 patients with G1 tumours had non-sN metastases. The mean tumour size in patients with non-sN involvement was 21.3mm (range, 12–40mm). Univariate test of association between clinical and histopathologic features and non-sN status showed that the primary tumour size (P=0.005) and the presence of lymphovascular invasion (P=0.000) were the only significant predictors of non-sN involvement. By logistic regression, primary tumour size (P=0.011), lymphovascular invasion (P=0.001), and size of sN micrometastases were the only variables remaining into the model, although the latter parameter was not statistically significant. Conclusions: In patients with sN micrometastases, primary tumour size and lymphovascular invasion significantly predict non-sN status; notably, no patient with T1a–T1b and/or G1 tumours had non-sN metastases so that they could be spared an unnecessary ALND. [Copyright &y& Elsevier]

Background and Objectives: Literature review suggests that the sentinel lymph node (sN) represents a reliable predictor of axillary lymph node status in breast cancer patients; however, some important issues, such as the optimisation of the technique for the intraoperative identification of the sN, the role of intraoperative frozen section examination of the sN, and the clinical implications of sN metastasis as regards the surgical management of the axilla, still require further confirmation. The authors aimed (1) to assess the feasibility of sN identification with a combined approach (vital blue dye lymphatic mapping and radioguided surgery, RGS) and the specific contribution of either techniques to the detection of the sN, (2) to determine the accuracy and usefulness of intraoperative frozen section examination of the sN in order to perform a one-stage surgical procedure, and (3) to define how the sN might modulate the therapeutic planning in different stages of disease., Materials and Methods: From October 1997 to June 2001, 334 patients with early-stage (T(1-2) N(0) M(0)) invasive mammary carcinoma underwent sN biopsy; the average age of patients was 61.5 years (range, 39-75 years). In a subset of 153 patients, both vital blue dye (Patent Blue-V) lymphatic mapping and RGS were used to identify the sN, and the relative contribution of each of the two techniques was assessed., Results: In the whole group, the sN was identified in 326 of 334 patients (97.6%), and 105 of 326 patients (37.3%) had positive axillary lymph nodes (pN+). In 9 of 105 pN+ patients, the definitive histologic examination of the sN did not show metastases but these were detected in non-sN, thus giving an 8.6% false-negative rate, a negative predictive value of 94.5% (156/165), and an accuracy of 96.5% (252/261). As regards the specific contribution of the two different techniques used in the identification of the sN, the detection rate was 73.8% (113/153) with Patent Blue-V alone, 94.1% (144/153) with RGS alone, and 98.7% (151/153) with Patent Blue-V combined with RGS (P < 0.001). Noteworthy, whenever the sN was identified, the prediction of axillary lymph node status was remarkably similar (93-95% sensitivity; 100% specificity; 95-97% negative predictive value, and 97-98% accuracy) whichever of the three procedures was adopted (Patent Blue-V alone, RGS alone, or combined Patent Blue-V and RGS). Intraoperative frozen section examination was performed in 261 patients, who had at least one sN identified, out of 267 patients who underwent complete axillary dissection; 170 patients had histologically negative sN (i.o. sN-) and 91 patients histologically positive sN (i.o. sN+). All 91 i.o. sN+ were confirmed by definitive histology, whereas in 14 of 170 i.o. sN- patients (8.2%) metastases were detected at definitive histology. As regards the correlation between the size of sN metastasis, the primary tumour size, and the status of non-sN in the axilla, micrometastases were detected at final histology in 23 patients and macrometastases in 82 patients. When only micrometastases were detected, the sN was the exclusive site of nodal metastasis in 20 of 23 patients (86.9%) while in 3 patients with tumour size larger than 10 mm micrometastases were detected also in non-sN. Macrometastases were never detected in pT(1a) breast cancer patients; the sN was the exclusive site of these metastases in 30 patients (36.6%), while in 52 patients (63.4%) there were metastases both in sN and non-sN., Conclusions: Sentinel lymphadenectomy can better be accomplished when both procedures (lymphatic mapping with vital blue dye and RGS) are used, because of the significantly higher sN detection rate, although the prediction of axillary lymph node status remains remarkably similar whichever method is used. The intraoperative frozen section examination proved to be rather accurate in predicting the actual pathologic status of the sN, with a negative predictive value of 91.8%; in 35% of patients it allowed sN biopsy and axillary dissection to be performed in a one-stage surgical procedure. Finally, specific clinical and histopathologic features of the primary tumour and sN might be used to tailor the loco-regional and systemic treatment in different clinical settings, such as in ductal carcinoma in-situ (DCIS), early-stage invasive breast cancer, and patients with large breast cancer undergoing neo-adjuvant CT for breast-saving surgery as well as elderly patients with operable breast cancer.

Axillary lymph node status represents the most important prognostic factor in patients with operable breast cancer. A severe limitation of this technique is the relatively high rate of false negative sentinel lymph nodes (>5%). We studied 284 patients suffering from breast cancer; 264 had T1 tumors (16 T1a, 37 T1b and 211 T1c), while 20 had T2 tumors. All patients underwent lymphoscintigraphy 18-h before surgery. At surgery, 0.5 mL of patent blue violet was injected subdermally, and the sentinel lymph node (SN) was searched by gamma probe and by the dye method. The surgically isolated SN was processed for intraoperative and delayed examinations. The SN was successfully identified by the combined radioisotopic procedure and patent blue dye technique in 278/284 cases (97.9%). Analysis of the predictive value of the SN in relation to the status of the axillary lymph nodes was limited to 191 patients undergoing standard axillary dissection irrespective of the SN status. Overall, 63/191 (33%) identified SNs were metastatic, the SN alone being involved in 37/63 (58.7%) patients; a positive axillary status with negative SN was found in 10/73 (13.7%) patients with metastatic involvement. In T1a-T1b patients the SN turned out to be metastatic in 9/53 patients (17.0%). In 7/9 patients the SN was the only site of metastasis, while in 2/9 patients other axillary lymph nodes were found to be metastatic in addition to the SN. None of the 44 patients in whom the SN proved to be non-metastatic showed any metastatic involvement of other axillary lymph nodes. Our results demonstrate a good predictive value of SN biopsy in patients with breast cancer; the predictive value was excellent in those subjects with nodules smaller than 1 cm.

Recent studies have demonstrated the possibility of identifying the sentinel lymph node (sN) as a reliable predictor of axillary lymph node status in both cutaneous melanoma and breast cancer. However, some important issues need further definition: (1) optimization of the technique for intraoperative detection of the sN; (2) predictive value of the sN as regards axillary lymph node status, and (3) reliability of intraoperative histology of the sN. We report our experience in sN mapping in patients with Stage I-II breast cancer, with the aim of assessing: (1) the feasibility of lymphatic mapping with a combined approach (vital blue dye lymphatic mapping and radioguided surgery); (2) the agreement of the intraoperative histologic examination of the sN, by means of hematoxylin and eosin staining with final histology, and (3) the accuracy of sN histology as a predictor of axillary lymph node status.

Aims: Clinical records of patients undergoing surgery for breast cancer were reviewed in order to evaluate the prognostic role of lymph-node level involvement., Methods: From 1982 to 1991, 1143 patients had radical mastectomy or conservative surgery with total axillary dissection: 461 patients of mean age 57.1 years (range: 25-89 years) were lymph-node positive (pN1); 369 patients (80%) had radical mastectomy; and 92 patients (20%) had conservative treatment plus post-operative radiotherapy, with the same mean number (n = 16) of lymph nodes collected in the surgical specimen. Data were analysed for the number of positive lymph nodes and level of involvement., Results: Level I, Levels I + II and Levels I + II + III were involved in 44.9, 18 and 21.4% of patients, respectively; 'skip metastases' occurred in 72 of 461 pN1 patients (15.5%). A univariate analysis showed that prognosis was directly related to the number of levels involved (P < 0.001), and skip metastases had the same prognostic role as Level I involvement. The numbers of involved lymph-node levels and metastatic lymph nodes were well correlated; multivariate analysis showed that involvement of Levels I and III was independently correlated with prognosis. After adjustment for age and number of positive lymph nodes, the number of involved lymph-node levels was an independent prognostic factor, with highest predictability when all three lymph-node levels were positive (P = 0.009)., Conclusions: The prognostic value of lymph-node status should be defined not only by the number of metastatic lymph nodes, but also by the number of levels of involvement.

From May 1985 to June 1992, 375 patients were enrolled in a prospective controlled randomized clinical trial of peri-operative adjuvant chemotherapy (PAC) associated with long-term adjuvant chemo-endocrinotherapy in order to test the effectiveness of reducing the time interval between surgery and chemotherapy. The short-term surgical complications related to PAC are reported in order to verify whether such treatment might negatively affect the results of breast cancer surgery. One hundred and eighty-nine patients were randomly assigned to the peri-operative treatment, and 186 to the control group. Patients undergoing PAC received one course of cyclophosphamide (600 mg/sqm), epidoxorubicin (60 mg/ sqm), and 5-fluorouracil (600 mg/sqm) (CEF) within 48-72 h following surgery. Pathologically node-positive (N+) patients, who were given peri-operative CEF, had five further cycles of CEF alternated with six cycles of CMF (cyclophosphamide 600 mg/sqm, methotrexate 40 mg/sqm, and 5-fluorouracil 600 mg/sqm). All the other N+ patients received six cycles of CEF alternated with six cycles of CMF, starting within 30 days of surgery. No significant difference in post-operative morbidity was observed as regards median hospital stay (8 days), number of outpatient dressings (3.5 vs 3), seroma (51 (26.9%) vs 45 (24.2%)), lymphatic drainage (400 ml vs 409 ml), and post-operative infections, both local (10 vs 9) and in extraoperative foci (6 vs 7), in the study and control group, respectively. The toxicity of the peri-operative CEF was mainly gastrointestinal (nausea and vomiting, 55%; stomatitis, 3%), with only a small percentage (9%) reaching grades III-IV. Hair loss was the other main side effect (55%) with baldness in only 3%. Post-operative complications following radical breast cancer surgery seem to be primarily related to operative details (type of incision, accurate nerve-sparing technique, bleeding control, closure of subcutaneous and skin, drainage, aseptic technique) rather than to the one course of PAC.

From 1987 to 1992 at our Institute, 253 patients with non palpable breast lesions (NBPL) underwent a surgical excision. Fifty-one lesions (19.7%) were localized by an injection of a sterile 3% charcoal suspension under sonographic guide. The sonographic features of NBPL were classified as follows: positive in one case (2%), doubtful in 31 cases (60%) and negative in 19 cases (38%). According to our data the preoperative sonographic localization is a useful alternative procedure to stereotactis mammography in case of breast masses and/or areas of increased tissue density or distorted breast architecture.

The use of preoperative localization procedures for non-palpable breast lesions (NPBL) is becoming more and more widespread, increasing the detection of early breast cancers. From October 1987 to July 1992, at our Institution, 253 patients (pts) with clinically non-palpable lesions underwent surgical treatment. Of the 253 pts, the lesions have been localized in 95 cases by a needle system, and in the other 158 cases by a dye injection of a 3% sterile charcoal suspension using stereotactic method (118 cases) or sonography (40 cases). The patients' mean age was 53 years (range 30-75). Mammography revealed regular opacities in 133 cases, clustered microcalcification in 75, diffuse microcalcification in 24, opacities with irregular borders in nine and opacities with internal microcalcifications in 12. The histological findings showed benign breast disease in 175 cases (69.2%), borderline breast disease in 23 (9.1%) and malignancy in 55 (21.7%). The benign/malignant/borderline lesions ratio was 3.2:1. The majority (70%) of these malignant lesions were small cancers (less than 1 cm in diameter) and without lymph-node involvement. The biopsy cost (benign/malignant/borderline ratio, patients discomfort and cosmetic result) has been acceptable.

A phase I study to evaluate the use of i.p. infusion of recombinant interleukin-2 (rIL-2) was planned. The following dose levels were calculated: 0.1, 0.3, 1.0, 3.0 and 10 mg/m2/day for 14 days, but only the second levels were reached. In this trial the acute toxic effects at this dosage included cardiac ischemia, transient liver impairment and septic peritonitis. The maximum tolerated dose (MTD) was 0.3 mg/m2/day for 14 days. In addition, two patients developed peritoneal fibrosis. No objective responses were observed. Therefore, in order to explore the biological activity of low (nontoxic) doses, three patients (one untreated and two previously treated with rIL-2) were infused with 0.01 and 0.03 mg/m2/day for 7 days. Potentiation of cytolytic activities in peritoneal lymphocytes and activation of a lymphokine cascade in the ascitic fluid were observed at doses ranging from 0.03 mg/m2/day to 0.3 mg/m2/day. These findings in association with the toxic effects observed at the MTD suggest the use of the minimum effective dose for future locoregional immunotherapeutic protocols.

Surgery is the treatment of choice for thyroid cancer, often followed by I131 and thyroid hormone to control the local residual tumor and distant metastasis. Hundred and sixty-two patients with thyroid disease underwent surgery at the Division of Surgical Oncology of the Cancer Institute in Genoa. Thirty cases presented no malignant hot thyroid nodules, 37 of the other 132 cases were cancers (28%). In 23 cases (62%), the pathological diagnosis was papillary carcinoma, in ten cases (27%) follicular carcinoma, in four (11%) medullary carcinoma. In 13 cases (35%) (ten papillary carcinoma, two follicular carcinoma, one medullary carcinoma) the lesion was multicentric. Our data suggest that total thyroidectomy, performed in two steps, in most cases does not carry important post-operative morbidity but offers the greatest potential for cure. In our cases only one patient died (of the cancer). After radical surgery it is possible to detect and treat metastases by I131.

Estrogen (ER) and progesterone (PgR) receptors were evaluated in the tumor tissue (T) and in the mammary gland far from malignancy (D) in 36 breast cancers. Results were correlated with the pathological grading of the tumor and the axillary nodal status. It is suggested that a lower cancer malignancy with negative nodes and lower values of pathological grading (G1-G2) may be associated with a high level of ER in the mammary parenchyma far from the tumor (D).

In a phase-I-study recombinant interleukin-2 (rIL-2) in a dose from 0.01 to 0.3 mg/m2/day for 7 to 14 days was infused intraperitoneally. Side effects were fever and fluid retention. 2 patients showed a bacterial peritonitis after paracentesis. The investigations showed that the intraperitoneal (i.p.) administration of interleukin-2 activates the whole lymphokine cascade.

A case of retroperitoneal infectious myositis is described. The symptoms of infectious myositis may be confused with those of other more frequent soft tissue pathologies (haematoma and sarcomata). This infection is more frequent in countries with a tropical climate. The most frequent aetiological agent is Staphylococcus aureus. This paper reports on the diagnostic and therapeutic problems of this disease as recently observed at the Division of Surgical Oncology of the National Cancer Institute in Genoa.