Effect of a combined surgery, re-irradiation and hyperthermia therapy on local control rate in radio-induced angiosarcoma of the chest wall.

PURPOSE: Radiation-induced angiosarcoma (RAS) of the chest wall/breast has a poor prognosis due to the high percentage of local failures. The efficacy and side effects of re-irradiation plus hyperthermia (reRT + HT) treatment alone or in combination with surgery were assessed in RAS patients. PATIENTS AND METHODS: RAS was diagnosed in 23 breast cancer patients and 1 patient with melanoma. These patients had previously undergone breast conserving therapy (BCT, n = 18), mastectomy with irradiation (n=5) or axillary lymph node dissection with irradiation (n = 1). Treatment consisted of surgery followed by reRT + HT (n = 8), reRT + HT followed by surgery (n = 3) or reRT + HT alone (n = 13). Patients received a mean radiation dose of 35 Gy (32-54 Gy) and 3-6 hyperthermia treatments (mean 4). Hyperthermia was given once or twice a week following radiotherapy (RT). RESULTS: The median latency interval between previous radiation and diagnosis of RAS was 106 months (range 45-212 months). Following reRT + HT, the complete response (CR) rate was 56 %. In the subgroup of patients receiving surgery, the 3-month, 1- and 3-year actuarial local control (LC) rates were 91, 46 and 46 %, respectively. In the subgroup of patients without surgery, the rates were 54, 32 and 22 %, respectively. Late grade 4 RT toxicity was seen in 2 patients. CONCLUSION: The present study shows that reRT + HT treatment--either alone or combined with surgery--improves LC rates in patients with RAS.

No evidence of benefit from class-II compression stockings in the prevention of lower-limb lymphedema after inguinal lymph node dissection: results of a randomized controlled trial.

Graduated compression stockings have been advocated for prevention of lymphedema after inguinal lymph node dissection (ILND) although scientific evidence of their efficacy in preventing lymphedema is lacking. The primary objective of this study was to assess the efficacy of class II compression stockings for the prevention of lymphedema in cancer patients following ILND. Secondary objectives were to investigate the influence of stockings on the occurrence of wound complications and genital edema, health-related quality of life (HRQoL) and body image. Eighty patients (45 with melanoma, 35 with urogenital tumors) who underwent ILND at two specialized cancer centers were randomly allocated to class II compression stocking use for six months or to a usual care control group. Lymphedema of the leg and genital area, wound complications, HRQoL, and body image were assessed at regular intervals prior to and up to 12 months after ILND. No significant differences were observed between groups in the incidence of edema, median time to the occurrence of edema, incidence of genital edema, frequency of complications, HRQoL, or body image. Based on the results of the current study, routine prescription of class II graduated compression stockings after ILND should be questioned and alternative prevention strategies should be considered.

Therapeutic surgical management of palpable melanoma groin metastases: superficial or combined superficial and deep groin lymph node dissection.

BACKGROUND: Management of patients with clinically detectable lymph node metastasis to the groin is by ilioinguinal or combined superficial and deep groin dissection (CGD) according to most literature, but in practice superficial groin dissection (SGD) only is still performed in some centers. The aim of this study is to evaluate the experience in CGD versus SGD patients in our center. METHODS: Between 1991 and 2009, 121 therapeutic CGD and 48 SGD were performed in 169 melanoma patients with palpable groin metastases at our institute. Median follow-up was 20 and, for survivors, 45 months. RESULTS: In this heterogeneous group of patients, overall (OS) and disease-free survival, local control rates, and morbidity rates were not significantly different between CGD and SGD patients. However, CGD patients had a trend towards more chronic lymphedema. Superficial lymph node ratio, the number of positive superficial lymph nodes, and the presence of deep nodes were prognostic factors for survival. CGD patients with involved deep lymph nodes (24.8%) had estimated 5-year OS of 12% compared with 40% with no involved deep lymph nodes (p=0.001). Preoperative computed tomography (CT) scan had high negative predictive value of 91% for detection of pelvic nodal involvement. CONCLUSIONS: This study demonstrated that survival and local control do not differ for patients with palpable groin metastases treated by CGD or SGD. Patients without pathological iliac nodes on CT might safely undergo SGD, while CGD might be reserved for patients with multiple positive nodes on SGD and/or positive deep nodes on CT scan.

Long-term outcome of isolated limb perfusion with tumour necrosis factor-α for patients with melanoma in-transit metastases.

BACKGROUND: The use of tumour necrosis factor (TNF) α in isolated limb perfusion (ILP) for in-transit melanoma metastasis is not uniformly accepted. This article reports the long-term results of adding TNF-α to standard melphalan-based ILP (TM-ILP) for treatment of melanoma in-transit metastases. METHODS: Data for patients treated between 1991 and 2005 were retrieved from a prospectively maintained database. Hyperthermic ILP was performed with 1-4 mg TNF-α. With a median potential follow-up of 13 years, response rates, time to local progression and disease-specific survival were analysed in relation to standard baseline factors. RESULTS: Some 118 TM-ILPs were analysed in 105 patients, 54 for stage IIIA, 50 for stage IIIAB and 14 for stage IV disease. The overall response rate was 93·2 per cent; the response was complete in 67·8 per cent and partial in 25·4 per cent. The response rate was significantly influenced by stage of disease (IIIA versus IIIAB; P = 0·006). The complete response was maintained until the end of follow-up in 35 patients (33·3 per cent), and local control was achieved with one additional intervention in 12 others (11·4 per cent). Local progression occurred after 66 ILPs (55·9 per cent). Number of in-transit metastases (P = 0·008) and complete response after ILP (P < 0·001) were strong prognostic factors for time to local progression. The 5-year disease-specific survival rate was 27·3 per cent; survival was positively influenced by age, stage of disease, previous ILP and complete response after ILP. CONCLUSION: ILP with TNF-α may obtain long-term local control in selected patients with in-transit metastases from melanoma.

Forequarter amputation for malignancy.

BACKGROUND: Forequarter amputation (FQA) is an important treatment for malignant disease of the shoulder girdle. The aim of this study was to elucidate its role in surgical oncology. METHODS: This retrospective study analysed 40 patients who had an FQA. In nine, the chest wall was resected. The most frequent diagnoses were soft-tissue sarcoma (28 patients) and recurrent breast cancer (five). RESULTS: Median follow-up was 16 (range 1-184) months. The 1-year, 2-year and 5-year overall survival for patients with malignant disease was 71, 59 and 38 per cent respectively. The median time to local recurrence (eight patients) was 4 (range 1-19) months. Thirty-two patients had curative FQA with a 1-year, 2-year and 5-year overall survival of 90, 75 and 48 per cent respectively, and a median overall survival of 51 months. The 5-year overall and disease-free survival for soft-tissue sarcoma was 41 and 26 per cent respectively. Eight patients had a palliative FQA with a median survival of 5 (range 1-12) months. CONCLUSION: In locoregional disease such as sarcoma, FQA may offer the only possibility of cure. However, in patients with axillary metastasis, FQA has no impact on survival, although local control may improve the patient's quality of life.

Should internal mammary chain (IMC) sentinel node biopsy be performed? Outcome in 90 consecutive non-biopsied patients with a positive IMC scintigraphy.

INTRODUCTION: Although the status of the regional lymph nodes is an important determinant of prognosis in breast cancer, harvesting sentinel nodes (SN) detected in the internal mammary chain (IMC) is still controversial. AIMS: To determine in how many patients a positive IMC-SN might change the systemic or locoregional adjuvant therapy, with a possible benefit in outcome. PATIENTS AND METHODS: During 6 1/2 years data of T1-2 breast cancer patients, having an SN procedure, were prospectively collected. Our policy was not to explore the IMC even if it was the only localization of an SN. RESULTS: In 86 of 571 patients lymphoscintigraphy showed an IMC-SN. In 64 of these, the axillary SN was negative and only 25 of these patients did not have an indication for adjuvant systemic treatment based on their tumor characteristics. In the literature, IMC metastases are found in 0-10% of axillary negative patients. Routine IMC-SN biopsies would have resulted in an indication for adjuvant systemic therapy in 2-3 of our patients. Four parasternal recurrences were found during a median follow-up of 51 months. CONCLUSIONS: Harvesting IMC-SNs is a procedure of which only a limited number of patients have therapeutical benefit. Even with a thorough selection of patients, the extra morbidity of the procedure should be weighed against the potential benefit for the patient.

Who is prone to high levels of distress after prophylactic mastectomy and/or salpingo-ovariectomy?

BACKGROUND: The present study aimed to assess predictors of distress after 'prophylactic mastectomy (PM) and salpingo-ovariectomy (PSO), in order to enable the early identification of patients who could benefit from psychological support. PATIENTS AND METHODS: General distress and cancer-related distress were assessed in 82 women at increased risk of hereditary breast and/or ovarian cancer undergoing PM and/or PSO, before and 6 and 12 months after prophylactic surgery. Neurotic lability and coping were assessed before surgery. RESULTS: Cancer-related distress and general distress at both follow-up moments were best explained by the level of cancer-related and general distress at baseline. Being a mutation carrier was predictive of increased cancer-related distress at 6-month follow-up (but not at 12 months), and of lower general distress 12 months after prophylactic surgery. Also, coping by having comforting thoughts was predictive of less cancer-related distress at 6-month follow-up. CONCLUSIONS: Genetically predisposed women who are at risk of post-surgical distress can be identified using one or more of the predictors found in this study. Exploration of and/or attention to cancer-related distress and coping style before prophylactic surgery may help physicians and psychosocial workers to identify women who might benefit from additional post-surgical support.

The course of distress in women at increased risk of breast and ovarian cancer due to an (identified) genetic susceptibility who opt for prophylactic mastectomy and/or salpingo-oophorectomy.

The levels and course of psychological distress before and after prophylactic mastectomy (PM) and/or prophylactic salpingo-oophorectomy (PSO) were studied in a group of 78 women. General distress was measured through the hospital anxiety and depression scale (HADS), cancer-related distress using the impact of events scale (IES). Measurement moments were baseline (2-4 weeks prior to prophylactic surgery), and 6 and 12 months post-surgery. After PM, anxiety and cancer-related distress were significantly reduced, whereas no significant changes in distress scores were observed after PSO. At one year after prophylactic surgery, a substantial amount of women remained at clinically relevant increased levels of cancer-related distress and anxiety. We conclude that most women can undergo PM and/or PSO without developing major emotional distress. More research is needed to further define the characteristics of the women who continue to have clinically relevant increased scores after surgery, in order to offer them additional counselling.

Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases.

AIM OF THE STUDY: Results on tumour characteristics and survival of hereditary breast cancer (BC), especially on BRCA2-associated BC, are inconclusive. The prognostic impact of the classical tumour and treatment factors in hereditary BC is insufficiently known. METHODS: We selected 103 BRCA2-, 223 BRCA1- and 311 non-BRCA1/2 BC patients (diagnosis 1980-2004) from the Rotterdam Family Cancer Clinic. To correct for longevity bias, analyses were also performed while excluding index patients undergoing DNA testing 2 years after BC diagnosis. As a comparison group, 759 sporadic BC patients of comparable age at and year of diagnosis were selected. We compared tumour characteristics, the occurrence of ipsilateral recurrence (LRR) and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS) between these groups. By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in hereditary BC. RESULTS: We confirmed the presence of the particular BRCA1-phenotype. In contrast, tumour characteristics of BRCA2-associated BC were similar to those of non-BRCA1/2 and sporadic BC, with the exception of a high risk of CBC (3.1% per year) and oestrogen-receptor (ER)-positivity (83%). No significant differences between BRCA2-associated BC and other BC subgroups were found with respect to LRR, DDFS, BCSS and OS. Independent prognostic factors for BC-specific survival in hereditary BC (combining the three subgroups) were tumour stage, adjuvant chemotherapy, histologic grade, ER status and a prophylactic (salpingo-)oophorectomy. CONCLUSIONS: Apart from the frequent occurrence of contralateral BC and a positive ER-status, BRCA2-associated BC did not markedly differ from other hereditary or sporadic BC. Our observation that tumour size and nodal status are prognostic factors also in hereditary BC implies that the strategy to use these factors as a proxy for ultimate mortality appears to be valid also in this specific group of patients.

Long-term prognosis of primary retroperitoneal soft tissue sarcoma.

AIMS: To evaluate the result of treatment and long-term outcome of a population-based cohort of patients with retroperitoneal soft tissue sarcoma (RSTS). METHODS: Between 1 January 1989 and 1 January 1994, 143 patients diagnosed as having primary RSTS were selected from a national pathology database (PALGA) in the Netherlands. In this population-based group of patients, the result of surgery, overall survival (OS) and disease-free survival (DFS) were analysed as well as factors affecting OS and DFS. Median follow-up was 10.2 years. RESULTS: Operative treatment resulted in a complete tumour resection in 55% of the patients (n=78), low- and intermediate-grade tumours were more often completely resected than high-grade tumours (P=0.016). Five- and 10-year cumulative OS was 39% and 21%, respectively, while DFS was 22% and 17%, respectively. In a multivariate analysis low malignancy grade (P=0.017) and a complete tumour resection (P<0.001) were associated with better OS. CONCLUSIONS: Complete tumour resection and low malignancy grade were independent favourable prognosticators. However, these factors were related too, since surgical success was influenced by malignancy grade.

Morbidity and prognosis after therapeutic lymph node dissections for malignant melanoma.

Melanoma patients with clinically evident regional lymph node metastases are treated with therapeutic lymph node dissections (TLNDs). The aim of this study was to evaluate morbidity and mortality following TLND in our institution. Moreover, disease-free (DFS) and overall (OS) survival were evaluated and factors that influence prognosis after TLND were assessed. Between 1982 and 2005, 236 patients underwent a TLND. Patients, who received a palliative LND or a sentinel node procedure, were not included. The median Breslow thickness was 2.4mm. Ulceration was present in 23% of patients and unknown in 66%. 37 patients had unknown primary tumors. There were 129 ilio-inguinal, 50 axillary and 61 cervical dissections performed. 37% of the patients experienced at least one operation related complication. The most frequently seen complications were wound infections/necrosis and chronic lymph edema. Ilio-inguinal dissection patients experienced significantly more complications and a longer duration of hospitalization compared to axillary or cervical patients. The duration of hospitalization has been reduced in recent years from 12 to 5days. The mean follow-up was 29months. Kaplan-Meier estimated 5-year regional control was 79%, 5-year DFS was 19% and 5-year OS was 26%. The number of positive lymph nodes, the site of the primary tumor and extra capsular extension (ECE) were independent prognostic factors for DFS and only site and ECE for OS. In conclusion, TLND for stage III melanoma is accompanied with considerable short-term complications, and can achieve regional control and potential curation in approximately one in every four patients.

[Oncoplastic surgery of the breast: a combination of oncological and plastic surgery]. / Oncoplastische chirurgie van de mamma: combinatie van oncologische en plastische chirurgie.

The term oncoplastic surgery refers to surgery on the basis of oncological principles during which the techniques of plastic surgery are used, mostly for reconstructive and cosmetic reasons. The advantage ofoncoplastic surgery for breast cancer is the possibility of performing a wider excision of the tumour with a good cosmetic result. Oncoplastic surgery is a broad concept that can be used for several different combinations of oncological surgery and plastic surgery: mastectomy and immediate reconstruction of the breast, partial mastectomy and reconstruction, excision of the tumour by reduction mammoplasty, and tumour excision followed by remodelling mammoplasty. Oncoplastic surgery requires careful preoperative planning, which is essential in all forms of breast-sparing surgery. Oncoplastic principles can easily be applied to basic breast-sparing surgery, but one can also choose to increase the possibilities of breast surgery by organising good cooperation between the oncological surgeon and the plastic surgeon.

[Long-term results of the multidisciplinary surgical treatment of non-small-cell bronchial carcinoma in the superior sulcus (Pancoast tumour): a retrospective study]. / Langetermijnresultaten van de multidisciplinaire chirurgische behandeling van niet-kleincellig bronchuscarcinoom in de thoraxkoepel (pancoasttumor); retrospectief onderzoek.

OBJECTIVE: To establish the long-term results of a combination of radiotherapy or chemoradiotherapy and surgery for the treatment of patients with a Pancoast tumour in the Erasmus MC-Daniel den Hoed, Rotterdam, the Netherlands, with special attention for the prognostic factors. DESIGN: Retrospective. METHODS: During the period from 1 January 1991 to 31 December 2004, 36 patients underwent surgical treatment combined with radiotherapy or chemoradiotherapy for a non-small-cell bronchial carcinoma with invasion of the superior sulcus. The study was terminated on 31 January 2006. The data were analysed according to the intention-to-treat principle, with overall survival and disease-free survival as the outcome variables. Cox regression analysis revealed differences between the subgroups on the basis of which prognostic factors could be studied. RESULTS: 36 patients with a non-small-cell bronchial carcinoma invading the superior sulcus (Pancoast tumour) underwent multidisciplinary treatment consisting of pre-operative radiotherapy (since 2002 concomitant chemoradiotherapy), superior-sulcus resection and (partial) lung resection with intra-operative brachytherapy. 2 patients died postoperatively. In 80% of the patients there was a positive histological effect of the preoperative treatment. The median follow-up was 26 months. The 2-year overall and disease-free survival was 45 and 31%, respectively, and at 5 years this was 28 and 19%. These results were comparable with those for stage IIB lung cancer without invasion. Favourable prognostic factors were: at least 75% necrosis of the tumour after pre-treatment, lack of positive mediastinal lymph nodes, and younger age.

High positive sentinel node identification rate by EORTC melanoma group protocol. Prognostic indicators of metastatic patterns after sentinel node biopsy in melanoma.

Methods to work-up sentinel nodes (SN) vary considerably between institutes. This single institution study evaluated the positive SN-identification rate of the EORTC Melanoma Group (MG) protocol and investigated the prognostic value of the SN status regarding disease-free survival (DFS) and overall survival (OS) and evaluated the locoregional control after the SN procedure. Multivariate and univariate analyses using Cox's proportional hazard regression model was employed to assess the prognostic value of covariates regarding DFS and OS. The positive SN-identification rate was 29% at a median Breslow thickness of 2.00 mm and the false-negative rate was 9.4%. Breslow thickness and ulceration of the primary correlated with SN status. SN status, ulceration and site of the primary tumour correlated with DFS. SN status and ulceration of the primary correlated with OS. The in-transit metastasis rate correlated with SN-positivity, Breslow thickness and ulceration. Projected 3-year OS was 95% in SN-negative and 74% in SN-positive patients. Transhilar bivalving of the SN with step sections from the central planes is simple and had a high SN-positive detection rate of about 30%. The SN status is the most important predictive value for DFS and OS. In-transit metastasis rates correlated with SN-positivity, Breslow thickness and ulceration of the primary.

Isolated limb perfusion for melanoma patients--a review of its indications and the role of tumour necrosis factor-alpha.

AIMS: The treatment of melanoma in-transit metastases (IT-mets) can vary widely and is dependant on the size and the number of the lesions. When multiple, large lesions exist, isolated limb perfusion (ILP) has established itself as an attractive treatment option with high response rates. METHODS: Review on the various methods of treatment of melanoma in-transit metastases, with a focus on isolated limb perfusion. A Medline based literature search was performed for articles relating to this topic. Additional original papers were obtained from citations in those identified by the initial search. Indications and results are discussed and the extra value of tumour necrosis factor (TNF) is evaluated. RESULTS: ILP with Melphalan results in complete response rates of 40-82% and showed to be 54% in a large retrospective meta-analysis. The addition of TNF can improve these completes response rates (59-85%) and although no data from randomized controlled trials are available, it seems of particular value in large, bulky lesions or in patients with recurrent disease after previous ILP. CONCLUSIONS: TNF-based ILP has earned a permanent place in the treatment of patients with melanoma IT-mets. In patients with a high tumour burden, TNF-based ILP is the most efficacious procedure to obtain local control and achieve limb salvage.

Sentinel node biopsy for clear cell sarcoma.

Clear cell sarcoma (CCS), also known as clear cell sarcoma of tendons and aponeuroses or malignant melanoma of soft tissue, is a rare malignant tumor and is histogenitically related to melanoma. The aim of this study was to describe our experience with the sentinel node (SN) procedure for CCS patients and to discuss the potential value of this technique for CCS patients. Five patients with a subcutaneous CCS, who underwent an SN procedure, are described. Two patients had positive SNs, with additional tumor positive nodes in both lymph node dissection specimens. Only the patients with tumor positive SNs developed recurrent disease during an average follow-up of 33 months. None of the negative SN patients developed recurrent disease and all were alive after an average follow-up of 39 months. SN status seems to predict additional nodal involvement and recurrent disease as well as survival. The SN procedure might be a useful and accurate staging procedure in CCS patients, comparable to the situation in melanoma.

Aggressive angiomyxoma: multimodality treatments can avoid mutilating surgery.

AIMS: Aggressive angiomyxoma is a soft-tissue tumour of the pelvi-perineum. The recurrence rate is high, and often extensive resections are performed with considerable morbidity. In search of alternative treatment methods we present our experience in seven patients. METHODS: The medical charts of seven patients treated in the last 20years were reviewed. Follow-up data were obtained. In addition, a literature review from 1994 to 2004 regarding treatment and clinical outcome was performed. RESULTS: All patients were female, and three were pregnant at the time of diagnosis. All patients underwent primary surgical treatment. In five patients the surgical margins were involved; one patient received adjuvant radiotherapy treatment. Three patients experienced a total of four recurrences after 2-10years. These patients were treated with selective embolisation or surgery. At present all patients are disease-free, with follow-up ranging from 2 to 20years after last treatment. CONCLUSION: Radical surgery does not seem to lead to a significant lower recurrence rate of aggressive angiomyxoma when compared to incomplete resection (R1), with or without radiotherapy or arterial embolisation. This casts doubt on the necessity of extensive surgery, especially in cases where an extensive surgical procedure will lead to great morbidity.

Repeat isolated limb perfusion with TNFalpha and melphalan for recurrent limb melanoma after failure of previous perfusion.

AIM: To assess the effectiveness of isolated limb perfusion (ILP) with tumour necrosis factor-alpha (TNFalpha) and melphalan for recurrent or persistent melanoma lesions after previous ILP. METHODS: Between 1978 and 2001, 21 patients (mean age 65, range 29-83 years) underwent repeat ILP for recurrent or persistent melanoma after a previous ILP. First ILPs had been performed with melphalan alone in 13 patients and with addition of TNFalpha in eight, for a median of nine lesions (interquartile (IQ) range 2-23 lesions). Repeat ILP was performed with TNFalpha and melphalan in all 21 patients for a median of nine lesions (IQ range 5-25 lesions). Median follow-up after repeat ILP was 18 months (IQ range 6-36 months). RESULTS: Thirteen patients attained a complete response (CR) after repeat ILP compared to 11 of 17 with measurable lesions after the first ILP. Nine patients relapsed after CR. Median limb recurrence-free survival was 13 months. Fourteen patients had mild acute regional toxicity after repeat ILP compared to 18 after the first ILP (n.s.). One patient underwent amputation for critical limb ischemia 10 months following repeat ILP. The limb salvage rate was 95%. Overall median survival was 62 months after CR compared to 13 months for those without CR (P=0.05). CONCLUSION: Repeat ILP with TNFalpha and melphalan is feasible after previous ILP with mild regional toxicity. The CR rate is relatively high and comparable to the first procedure with good limb recurrence-free survival and high limb salvage rate.

5-Year follow-up of sentinel node negative breast cancer patients.

AIM: To report the long-term results of sentinel node negative breast cancer patients treated without axillary lymph node dissection and the 5-year follow-up results of 149 patients. METHODS: The incidence of axillary-and local recurrences and second ipsilateral primary tumours was evaluated. The added value of annual ultrasound of the treated axilla, being part of the standard follow-up, was also evaluated. RESULTS: After a mean follow-up of 65 months (50-79) axillary recurrences were observed in four patients, local recurrences or ipsilateral second primary tumours were diagnosed in another seven patients. All axillary recurrences were diagnosed because of a palpable axillary mass; ultrasound in combination with fine needle aspiration cytology did not have an added value. CONCLUSION: It can be concluded that the incidence of axillary recurrences after negative SN is much lower than expected. There is no added value of US and FNAC of the axilla in the routine follow-up of SN negative patients.

Reasons for failure to identify positive sentinel nodes in breast cancer patients with significant nodal involvement.

AIM: To analyse causes of failure of sentinel node (SN) procedures in breast cancer patients and assess the role of pre-operative ultrasound examination of the axilla. METHODS: In 138 consecutive clinically node negative breast cancer patients with the primary tumour in situ a SN procedure with radiolabeled colloid and blue dye was performed. Radioactivity in the SN was scored as inadequate or adequate. The axillary lymph node dissection scored for number of involved nodes and presence of extranodal growth. RESULTS: In 53/138 patients, the SN was positive for tumour. Full axillary node dissection revealed that 58/138 were node positive. So in five patients the SN failed to predict true nodal status. In 3/5, the radioactive ratio (SN vs background) was inadequate. All were found to have extensive nodal involvement. The radioactivity ratio was inadequate in 37/138 patients. This ratio was inadequate in 10 of 15 patients with > or =4 positive nodes and 27 of 123 in patients with 0-3 positive nodes (p < 0.001). If extranodal growth was present the radioactive ratio was inadequate in 13 of 18 patients, whilst this was only the case in 24 of 120 patients without extranodal growth or metastases (p < 0.001). Ultrasound (US) examination and US-guided FNAC was able to pre-operatively identify 16 of the 26 patients with four or more metastases in the axilla. CONCLUSIONS: Extensive nodal involvement is an important cause of failure of the sentinel node biopsy. Pre-operative ultrasound examination of the axilla can avoid this in almost two thirds of these patients.