[Protocol for diagnostic assessment of sentinel lymph node in breast pathology: a proposal of SIAPEC-IAP, Piemonte Region, Italy].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to G Canavese.
Explore the source record for details and available documents.
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 </= 10 mm 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 21.3 mm (range, 12-40 mm). 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.
Explore the source record for details and available documents.
The possible relationship between gastric metaplasia and ulcerative lesions in an unusual case of ulcerative jejunitis not related to celiac disease and with extensive gastric metaplasia is discussed. Previous studies have described gastric metaplasia in duodenal ulcers on the basis of endoscopic data, and some authors maintain that acid secretion in metaplastic mucosa could represent a pathogenetic factor of ulcerogenesis, with a self-amplifying mechanism. In the absence of functional evidence, we could provide data, in a case of ulcerative jejunitis, about morphologic signs of acid secretion in gastric metaplastic epithelium using an antibody against HMFG-1, a good marker of acid-secreting fundic cells. Metaplastic areas demonstrated a focal positivity for HMFG-1, and these finding are suggestive of local acid secretion.
We report a patient who, 2 years after mastectomy and breast reconstruction using a permanent expander, developed metastatic carcinoma around the filling port of the prosthesis. We believe this is the first description of such a condition, the differential diagnosis of which includes a silicone granuloma.
PURPOSE: Capecitabine is an oral fluoropyrimidine with considerable activity and minimal myelosuppression and alopecia. This phase I study evaluated the addition of capecitabine to epirubicin/docetaxel combination therapy as first-line treatment for advanced breast cancer. PATIENTS AND METHODS: Twenty-three female patients with advanced breast cancer received capecitabine (765-1060 mg/m2 twice daily on days 1-14 of a 3-week treatment cycle) in combination with epirubicin and docetaxel (75 mg/m2 i.v. on day 1). RESULTS: The maximum tolerated dose of capecitabine was 985 mg/m2 and the principal dose-limiting toxicity was febrile neutropenia. No grade 3/4 anemia or thrombocytopenia occurred. There were no grade 4 non-hematological events and grade 3 events other than alopecia were rare. Alopecia occurred in all patients and treatment cycles, and asthenia occurred in all patients and in 84% of treatment cycles. Other frequent adverse events included nausea, vomiting, fever, paresthesia and elevated transaminase levels. An objective response to treatment was observed in 91% (95% confidence interval 72% to 99%) of patients. CONCLUSIONS: The addition of capecitabine to docetaxel/epirubicin combination therapy provides a well-tolerated and active first-line chemotherapy regimen in patients with advanced breast cancer, and merits phase II/III evaluation.
BACKGROUND AND OBJECTIVES: Recent studies have demonstrated that the sentinel lymph node (sN) can be considered a reliable predictor of axillary lymph node status in breast cancer patients. However, some important issues, such as optimization of the technique for the intraoperative identification of the sN, and the clinical implications of sN metastasis as regards the surgical management of the axilla still require further elucidation. The objectives of this study was to assess (1) 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, and (2) the correlation between the size of sN metastasis (micrometastasis < or = 2 mm; macrometastasis > 2), primary tumour size, and the status of nonsentinel nodes (nsN) in the axilla. METHODS: Between October of 1997 and December of 1999, 212 patients with breast cancer (average age: 61 years; range, 40-79 years) underwent sN biopsy before performing standard axillary dissection. 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: Overall, the sN was identified in 206 of 212 patients (97.1%); at histologic examination of all dissected nodes, 77 of 206 patients had positive nodes (37.3%). The false-negative rate was 6.5% (5/77), the negative predictive value was 96.3% (129/134), and accuracy was 97.6% (201/206). Among 72 patients with positive sN, micrometastases were detected in 21 cases and macrometastases in 51. When micrometastases only were observed, the sN was the exclusive site of nodal metastasis in 17 of 21 cases (80.9%); in the remaining 4 cases (19.1%), nsN metastases were detected in 3 of 14 pT1c patients (21.5%), and 1 of 5 pT2 patients (20%). Macrometastases were detected in patients with tumors classified as pT1b or larger: the sN was the exclusive site of metastasis in 3 of 4 pT1b patients (75%), in 14 of 29 pT1c patients (48.2%), and in 3 of 18 pT2 patients (16.6%). The specific contribution of the two different techniques used in the identification of the sN was evaluated; the detection rate was 73.8% (113 of 153) with Patent Blue-V alone, 94.1% (144 of 153) with RGS alone, and 98.7% (151 of 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) with each of the three procedures (Patent Blue-V alone, RGS alone, or combined Patent Blue-V and RGS). CONCLUSIONS: Sentinel lymphadenectomy can better be accomplished when both procedures (lymphatic mapping with vital blue dye and RGS) are used, due to the significantly higher sN detection rate, although the prediction of axillary lymph node status remains remarkably similar with each one of the methods assessed. That patients with small tumours (<1 cm) and sN micrometastasis are very unlikely to harbour metastasis in nsN should be considered when planning randomised clinical trials aimed at defining the effectiveness of sN guided-axillary dissection.
PURPOSE: To evaluate if chemotherapy (CT) dose-intensification jeopardizes radiotherapy (RT) dose-intensity (DI). PATIENTS AND METHODS: From 1992 to 1997, 247 stage I-II breast cancer patients, treated with conserving surgery, were treated at the National Cancer Institute of Genoa in a randomized study comparing the same CEF regimen delivered every two weeks (CEF14) or three weeks (CEF21). RT was applied to the residual breast at a total dose of 50 Gy in five weeks. Allowance was made for treatment at 2.3 Gy per fraction in order to compensate for gaps (hypofractionation). Radiotherapy DI was expressed as the average total dose received each week, i.e., 'weekly dose-rate' (WDR). The effect of various tumour, treatment and patient-related factors on the endpoint (a delivered WDR of RT < 9.5 Gy) was investigated by univariate analysis. Factors found to have P-value < or = 0.20 were entered in multivariate analysis. RESULTS: All but three patients (244 of 247, 98.8%) received a cumulative total dose of RT within +/- 10% of that planned. Moreover, most of them (197 of 247, 79.8%) received an average WDR of > or = 9.5 Gy/wk. With univariate analysis the probability of WDR < 9.5 Gy/wk significantly correlated with age, menopausal status, concomitant administration of RT and CT, and white blood cell toxicity. Moreover, a positive effect on WDR was found in patients treated at 2.3 Gy per fraction. The type of treatment (CEF14 vs. CEF21) did not affect the probability of WDR < 9.5 Gy/wk. With multivariate analysis, age (< or = 55 vs. > 55 years, RR = 3.99, 95% CI: 1.89-8.42, P = 0.0003), RT fractionation (conventional vs. hypofractionation, RR = 0.32, 95% CI: 0.15-0.68, P = 0.017) and WBC toxicity (none vs. some, RR = 1.54, 95% CI: 1.06-2.22, P = 0.027) were independent predictors of WDR < 9.5 Gy. Regarding the CT-RT overlap, patients receiving more than two cycles of chemotherapy during radiotherapy had an increased risk of RT delay compared to other patients (RR = 3.74, 95% CI: 1.44-9.48, P = 0.0063). CONCLUSIONS: There is no evidence of a direct effect of CT dose-density on dose-intensity of RT. However, the concomitant use of CT and RT reduces the possibility of giving a full dose-intensity of RT.
The immunohistochemical expression of the inhibitors of cyclin-dependent kinases p21 and p27 was investigated in 109 endocrine tumors of the pancreas and gastrointestinal tract and compared with that of Ki67 and p53. p21 was found to be scarcely expressed without significant differences between benign and malignant or between differentiated and undifferentiated tumors. This suggests no relationship between changes in p21 levels and clinical behavior in these endocrine tumors. p27 was found to be highly expressed in differentiated neoplasms and proved to be inversely related to Ki67 labeling (P =.02), which was usually low. These data indicate that p27 may have an important inhibiting role on the low proliferation rate of the tumors. Moreover, the protein may have a role in the resistance of differentiated endocrine tumors to chemotherapeutic agents. p27 high-expressor neoplasms were frequent in either benign (70.6%) or malignant (81.4%) differentiated tumors, thus not allowing the use of this protein for the differential diagnosis of malignant neoplasms as suggested for endocrine tumors of parathyroid and pituitary. Poorly differentiated endocrine carcinomas, which differred from the differentiated tumors for their very high Ki67 levels and frequent p53 expression, showed low or absent p21 and p27 in most cases. Classical midgut carcinoids were characterized by a sharp discrepancy between malignant behavior and very bland proliferative pattern, with Ki67 and p27 expressions similar to that of benign tumors.
The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way through the lymphatic system, from the first to upper levels. Therefore, the first lymph node met (the sentinel node) will most likely be the first to be affected by metastasis, and a negative sentinel node makes it highly unlikely that other nodes are affected. Because axillary node dissection does not improve prognosis of patients with breast cancer (being important only to stage the axilla), sentinel lymph node biopsy might replace complete axillary dissection to stage the axilla in clinically N0 patients. Sentinel lymph node biopsy would represent a significant advantage as a minimally invasive procedure, considering that, after surgery, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Furthermore, histologic sampling errors can be reduced if a single (sentinel) node is assessed extensively rather than few histologic sections in a high number of lymph nodes per patient. Although the pattern of lymph drainage from breast cancer can be variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Therefore, considering that tumor lymphatics are disorganized and relatively ineffective, subdermal and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. (99m)Tc-labeled colloids with most of the particles in the 100- to 200-nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy because images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than that of background (at least 10:1 intraoperatively). After removal of the sentinel node, the axilla must be reexamined to ensure that all radioactive sites are identified and removed for analysis. The sentinel lymph node should be processed for intraoperative frozen section examination in its entirety, based on conventional histopathology and, when needed, immune staining with anticytokeratin antibody. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94%--97% in institutions where a high number of procedures are performed and approaches 99% when combined with the vital blue dye technique. At present, there is no definite evidence that negative sentinel lymph node biopsy is invariably correlated with negative axillary status, except perhaps for T1a-b breast cancers, with a size of < or =1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection on patients with a negative sentinel lymph node on the long-term clinical outcome of patients.
BACKGROUND AND OBJECTIVES: Axillary lymph node status is the most important prognostic factor in patients with operable breast cancer. 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. Sentinel lymph node identification proved feasible by either peritumoral dye injection (Patent Blue-V) or radiodetection, with identification rates of 65-97% and 92-98%, respectively. However, some important issues need further definition, namely (a) optimization of the technique for intraoperative detection of the sN, (b) predictive value of the sN with regard to axillary lymph node status, and (c) reliability of intraoperative histology of the sN. We reviewed our experience in sN detection in patients with stage I-II breast cancer to assess the feasibility and accuracy of lymphatic mapping, by vital blue dye or radioguided surgery, and sN histology as a predictor of axillary lymph node status. METHODS: Two groups of patients (55 and 48) were recruited between May 1996 and May 1997 and between October 1997 and February 1998; the patients of the first series underwent vital blue dye lymphatic mapping only, whereas those of the second series had a combined approach with both vital blue dye mapping and radioguided detection of the sN. RESULTS: In the first set of patients, the sN was identified in 36/55 patients (65.4%); sN histology predicted axillary lymph node status with a 77% sensitivity (10/13), a 100% specificity (23/23), an 88.5% negative predictive value (23/26), and an overall 91.5% accuracy (33/36). The sN was the quasi-elective site of lymph node metastases because in clinically N0 patients nodal involvement was 20-fold more likely at histology in sN than in non-sN (30% and 1.5%, respectively). In the second set of patients, 49 lymphadenectomies were performed because 1 patient had bilateral breast cancer; the sN was identified in 45/49 lymphadenectomies (92%). The sN was intraoperatively negative at frozen-section examination in 33 cases, and final histology confirmed the absence of metastases in 31/33 cases (94%), whereas in 2 cases (6%) micrometastases only were detected. Final histology of the sN predicted axillary lymph node status with an 87.5% sensitivity (14/16), a 100% specificity (29/29), a 93.5% negative predictive value (29/31), and an overall 95.5% accuracy (43/45). CONCLUSIONS: Sentinel lymphadenectomy can be better accomplished when both mapping techniques (vital blue dye and radioguided surgery) are used. In this group of patients, agreement of intraoperative histology of the sN with the final diagnosis was 94%, and sN histology accurately predicted axillary lymph node status in 43/45 lymphadenectomy specimens (95.5%) in which an sN was identified.
BACKGROUND AND OBJECTIVE: We performed a pilot study on 30 consecutive patients undergoing sentinel node (sN) biopsy by radioguided surgery and vital blue dye mapping to determine whether there is a single sN for each breast independent of tumor site or an sN specifically related to the site of the breast neoplasm. METHODS: There were 6 groups of 5 patients; each patient had a subdermal injection of radiotracer on the tumor site plus a second injection of radiotracer that was changed in every subset of patients to test whether modifying the site or the route of injection could have impaired the proper detection of the sN. RESULTS: "False" sN were detected only in patients who had a second injection of radiotracer away from the tumor site; this occurred in 2 of 5 patients (40%) in group I, in 3 of 5 patients (60%) in group II, in all patients in group III, and in 3 of 5 patients (60%) in group IV. The different route of injection (peritumoral or subdermal) always on the tumor site that was tested in groups V and VI did not impair the proper detection of the sN. CONCLUSIONS: Our findings support the hypothesis of a precise topographic correspondence between the primary tumor and its specific sN more than the existence of a first sN in the axillary basin, which indiscriminately drains all quadrants of the breast, like "a neck of a bottle." This should be considered for the proper selection of the injection site of either vital blue dye or radiopharmaceuticals.
The purpose of the present work was two-fold: 1) to evaluate the predictive value of the sentinel lymph node (sLN) versus the axillary-node status in patients with T1-T2 breast cancer, and 2) to form an experimental basis for a randomized trial in which one group of patients with non-metastatic sLN will not have axillary dissection. Of a group of 284 patients considered for this analysis, 264 had a T1 cancer (16 T1a, 37 T1b and 211 T1c), while 20 had a T2 cancer; 243 patients were in clinical stage N0 and 41 were N1. All patients underwent lymphoscintigraphy 18 hr before surgery: 10 MBq in 0.15 mL of 99mTc-human albumin nanocolloids (particle size between 50-80 nm) was injected subdermally at the cutaneous projection of the tumor. Static gamma-camera images were acquired every 10-15 minutes until scintigraphic identification of the sLN. At surgery, 1-2 mL of Patent-Blue Violet was injected subdermally, and the sLN was searched by gamma-probe and by the dye method. The surgically isolated sLN was processed for intraoperative Hematoxylin & Eosin (H&E) histology, then for delayed histological and immunohistochemical examinations. The sLN was successfully identified by the combined radioisotopic procedure and Patent-Blue dye technique in 278/284 cases (97.9%). The Patent-Blue dye technique alone identified fewer sLNs than the radioisotopic procedure alone (56.3% versus 97.2%). Analysis of the predictive value of the sLN as to the status of axillary lymph nodes was limited to 197 patients undergoing standard axillary dissection irrespective of the sLN status. Overall, 63/191 (33%) identified sLNs were metastatic, the sLN alone being involved in 37/63 (58.7%) patients; a positive axilla status with negative sLN was found in 10/73 patients with metastatic involvement (13.7% false-negative rate). In conclusion, subdermal lymphoscintigraphy was confirmed to be an effective technique for sLN mapping; the addition of Patent-Blue dye minimally improved intra-surgical identification of the sLN. There was a high, but not absolute, correlation between a negative sLN and a negative axilla.
In addition to suppressing breast cancer cell growth, retinoids potentiate growth inhibition in human breast cancer when tested in vitro and in vivo with tamoxifen and/or interferon. The purpose of this study was to ascertain the biologic effects of all-trans-retinoic acid (ATRA) administered alone and with tamoxifen +/- interferon and to identify the relationship between ATRA plasma concentrations and optimal biological dose (the lowest dose that produces a biological response). Three consecutive groups of 15 patients with locally advanced operable breast cancer were treated, in accordance with good clinical practice (GCP) requirements, with ATRA at 3 dose levels alone or with tamoxifen +/- alpha-interferon 2a at flat doses. After 3 weeks, the tumors were surgically removed. Biological parameters measured at the beginning (in biopsy tissue) and end (in surgical tissue) of the study were compared. The optimal biological dose for ATRA was 15 mg/m2/day. Treatments influenced tumor grade but not cell cycle kinetics (G0-G1 phase) or proliferation (Ki67 levels). ATRA induced progesterone receptors independent of dose level and co-administered drugs, but did not induce estrogen receptors when administered alone. Retinoic acid receptor (RAR)-alpha was not affected by treatment and RAR-alpha was moderately influenced whereas RAR-beta (concomitantly with transforming growth factor-beta) was induced in 33% of patients by ATRA alone. ATRA pharmacokinetics were dose- and time-dependent. Neither the ATRA + tamoxifen nor the ATRA + tamoxifen + interferon combinations potentiated the ATRA-induced biological changes. Future studies evaluating the role of RAR-beta as a biological marker of retinoid activity are warranted.
Twenty-one patients with histologically proven locally advanced breast cancer (LABC) were treated with a combined modality approach based on primary chemotherapy and radical modified mastectomy followed by adjuvant chemotherapy. Surgery was performed by using radioimmunoguided surgery (RIGS) technique with the preoperative injection of Iodine-125 labeled monoclonal antibodies (MoAbs) B72.3 anti-TAG (11 patients, Group A) and FO23C5 anti-carcinoembryonic antigen (CEA; 10 patients, Group B). The role of RIGS was defined at surgery by using an intraoperative hand-held gamma-detecting probe (GDP) to locate the primary tumor, possible clinically occult multicentric foci and ipsilateral lymph node metastases. In Group A, RIGS correctly defined the primary tumor in seven out of 11 patients (63.3%) and was able to find multicentric tumors in two out of four patients (50%). Positive lymph nodes were identified by RIGS in three out of eight patients (37.5%). In Group B, patients RIGS correctly located the primary in 4/10 cases (40%); in two RIGS-positive cases, the tumor was clinically not evident after primary chemotherapy (yT0). RIGS correctly identified multicentric foci of tumor in one out of two cases (50%). Correct lymph nodal RIGS assessment was observed in three out of nine patients (33.3%). No RIGS false-positive findings occurred in the 21 patients included in the study. RIGS appears to be a reliable technique for the intraoperative diagnosis and staging of breast cancer with a potential role especially when conservative surgery is planned after primary chemotherapy in LABC.
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.
A total of 38 suspected primary (26) or recurrent (12) breast tumors underwent enhanced magnetic resonance imaging (MRI) of the breast after positive (19) or uncertain (19) mammography. Spin echo T1-weighted images before and after intravenous administration of 0.15 mmol/kg Gd-DTPA, the latter ones at 1, 3, and 5 min, were obtained to characterize the mammographic findings. When contrast enhancement was absent, the same images were also obtained at 10 min. Evident and early focal enhancement was considered as an MRI sign of malignancy. All the lesions were submitted to histological examination (seven by core-biopsy only). Mammography results were 23 true positives and 15 false positives. MRI results were 22 true positives, 13 true negatives, 2 false positives, and 1 false negative. Twelve uncertain-mammography cases became true negatives at MRI; 1 uncertain-mammography case was the only MRI false negative; 1 positive-mammography cases became true negative at MRI. Resting on this limited series of patients, MRI is confirmed as a useful imaging technique after uncertain mammography.