Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial.

BACKGROUND: For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, axillary dissection might be overtreatment. We designed IBCSG trial 23-01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of maximum 5 cm. METHODS: In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (≤2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with ClinicalTrials.gov, NCT00072293. FINDINGS: Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5·0 (IQR 3·6-7·3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and five [corrected] regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87·8% (95% CI 84·4-91·2) in the group without axillary dissection and 84·4% (80·7-88·1) in the group with axillary dissection (log-rank p=0·16; HR for no axillary dissection vs axillary dissection was 0·78, 95% CI 0·55-1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3-4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection. INTERPRETATION: Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival. FUNDING: None.

Can we avoid axillary dissection in the micrometastatic sentinel node in breast cancer?

There is considerable interest in foregoing axillary dissection (AD) when the sentinel node (SN) is positive in early breast cancer, particularly when involvement is minimal (micrometastases or isolated tumor cells). To address this issue we analyzed outcomes in patients with a single micrometastatic SN who did not receive AD. We selected 377 consecutive patients treated at the European Institute of Oncology between 1999 and 2007 for invasive breast cancer. Classical and competing risks survival analyses were performed to estimate prognostic factors for axillary recurrence, first events and overall survival. Median age was 53 years (range 26-80); median follow-up was 5 years (range 1-9). Most (91.8%) patients received conservative surgery; 209 (55.4%) had only one SN (range 1-8). Five-year overall survival was 97.3%. There were 10 local events, 2 simultaneous local and axillary events, 6 axillary recurrences and 12 distant events. The cumulative incidence of axillary recurrence was 1.6% (95% CI 0.7-3.3). By multivariable analysis, tumor size and grade were significantly associated with axillary recurrence. The high five-year survival and low cumulative incidence of axillary recurrence in this cohort provide justification for the increasingly common practice of foregoing AD in women with minimal SN involvement, and suggest in particular that AD can safely be avoided in women with small, low-grade tumors. Nevertheless, a subset of patients might be at high risk of developing overt axillary disease and efforts should be made to identify such patients by ancillary analyses of the results of ongoing or recently published clinical trials.

Sentinel node biopsy in patients with previous breast aesthetic surgery.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard method for axillary staging of early breast cancer. Recent studies have focused on questioning the initial contraindication to the technique. There has been insufficient data to recommend SLNB in patients with previous aesthetic breast surgery. MATERIALS AND METHODS: Between April 2001 and June 2007, 70 patients with previous breast aesthetic surgery underwent SLNB. Fifty had a previous breast augmentation and 20 had breast reduction mammoplasty. All patients underwent lymphoscintigraphy with 99Tc according to our standard technique and sentinel node was identified in all cases. RESULTS: Mean age at cosmetic surgery was 38 years. Mean number of years from aesthetic surgery to the development of the tumour was 10 years. Forty-nine patients underwent conservative breast surgery and 21 patients underwent mastectomy. The sentinel node identification rate was 100%. SLN was positive in 23 patients (32%); there were 18 cases with macrometastasis and 7 cases with micrometastasis. After median follow-up of 19 months, no axillary recurrences have been observed. We observed two ipsilateral local recurrences, one contralateral tumour and one patient developed lung metastasis. CONCLUSIONS: Past history of breast augmentation or reduction is not a contraindication to SLNB technique.

Surgical closure of chest wall in noninflammatory locally advanced breast carcinoma with ulceration of the skin.

Patients with noninflammatory locally advanced breast cancer with ulceration of skin or muscle or parietal wall infiltration, better named "extended locally advanced breast cancer," may require cancer surgery and plastic reconstruction of the chest wall after multidisciplinary evaluation. The decision is made to improve quality of life, independently of prognosis, and severity of the disease. The aim of this study is to evaluate the best method for surgical closure of the chest wall and to check whether ablative surgery is an appropriate procedure in regards to the treatment of cancer. From October 1997 to June 2006, 27 patients with noninflammatory extended locally advanced breast cancer with ulceration of the skin, who were not candidate or did not respond to a neo-adjuvant treatment, underwent radical mastectomy and reconstructive surgery. Sixteen patients (59%) were affected by primary tumors of the breast, and eleven patients (41%) had local recurrence after mastectomy or conservative breast surgery. Two main techniques were used for breast reconstruction: transverse rectus-abdominis musculo cutaneous flap in 19 patients (70%), and a fasciocutaneous flap in eight patients (30%). The best procedure in each patient was chosen according to the extent of skin loss or previous radiotherapy to the chest wall. Fourteen patients (52%) died during the follow-up and the median length of survival was 16 months (range 3-79) in transverse rectus-abdominis musculo cutaneous group and 4 months (range 2-23) in fasciocutaneous flap group. The median length of follow-up after treatment for patients still alive was 32.5 months (range 0-96) in transverse rectus-abdominis musculo cutaneous flap group, and 18 months (range 8-41) in fasciocutaneous flap group. At the end of the follow-up, 10 patients were alive without evidence of disease and three patients developed metastatic lesion or local recurrence. The longest recorded disease free interval for a patient still alive and tumor free was 96 months. Only three patients (11%) had local complications: two wound infections and one partial necrosis of the transverse rectus-abdominis musculo cutaneous flap. Median hospital stay was 7 days (range 3-13) for transverse rectus-abdominis musculo cutaneous and 6 days (range 3-13) for fasciocutaneous flap. Our results confirmed that transverse rectus-abdominis musculo cutaneous group and fasciocutaneous flap flaps are good reconstructive options in patients with extended locally advanced breast cancer. Quality of life has improved in this group of patients, with acceptable survival periods and in some cases very important survival rates.

[A rare complication of colostomy]. / Complicatie rara a unei colostomii.

A case of a 64 years old female patient who had had a Miles operation 6 years ago for rectal cancer and at the present hospital admission she came in with a severe infection around her left colostomy. Initially, she presented a quite localized peristomal infection but, subsequently, the infection has evolved to an extensive necrotizing fasciitis of the abdomen, a large dehiscence of colostomy and severe sepsis. Repeated surgery and transverse colostomy, to put at rest infected left colostomy, plus aggressive medical treatment resulted in a good recovery, with the wounds healing and redo of the left colostomy. Now she is on the waiting list to get rid of the transverse colostomy.

Can titanium mesh influence local recurrence management after implant-based breast reconstruction?

INTRODUCTION: TiLOOP(®) Bra is a permanent titanium-coated polypropylene mesh currently used in post-mastectomy breast reconstruction with implants. This mesh is generally presented as inducing low-grade inflammatory reactions, but only few reports focused on its possible side effects. In the case described here, the use of the mesh led to minor clinical problems that needed to be clinically and surgically managed at the same time as a local relapse. CASE DESCRIPTION: A patient with high-grade ductal carcinoma in situ underwent primary surgery (nipple-sparing mastectomy and one-stage reconstruction using the TiLOOP(®) Bra mesh) and was subsequently referred for radiological and clinical investigation when various nodules became apparent during a follow-up physical examination. Prior to the histopathological proof, the diagnosis of local recurrence was complicated by the occurrence of an extensive granulomatous reaction in the fixation areas along with mild inflammatory changes scattered on the surface of the mesh. DISCUSSION AND EVALUATION: This case illustrates a side effect of titanium-coated permanent mesh in immediate implant-based reconstruction, i.e. the formation of granulomas in the inframammary fold, probably in the area where the mesh had been folded or fixed. We propose a safer technical approach to avoid the problem and a clinical management strategy for patients at high risk of local recurrence who develop granuloma-like nodules. CONCLUSIONS: A surgical technique is suggested to prevent granuloma formation. If, however, subcutaneous nodules that may be local recurrences do appear, they should not be interpreted by default as a granulomatous reaction, but should be fully investigated and possibly excised.

[Surgical treatment of locally advanced esophago-gastric cancer; preliminary results]. / Tratamentul chirurgical al cancerelor jonctiunii eso-gastrice local avansate; rezultate preliminare.

UNLABELLED: The aim of this paper is to sustain the palliative resection in neoplasm of the esophago-gastric junction, as a surgical approach that allows a better post-operative life comfort in comparison with simple gastrostomy. 62 observations with proximal neoplasm of the stomach (12.5%) were identified between January 1996-August 2001, representing 12.5% of the 496 patients with gastric neoplasm admitted in our unit in the same period. Out of these 62 cases, 55 (88.71%) underwent surgical procedures. Our attitude was aggressive in 25 cases. 40.32%, including the locally advanced lesions with palliative surgical indications (18 obs.). The other 30 patients underwent: 10 laparotomies, 5 gastrostomies and 15 jejunostomies. Local invasion to the neighboring organs imposed partial resection of the transverse colon--1 obs., of the transverse mesocolon--2 obs., and corporeo-caudal pancreatectomies--3 obs. The surgical approach was a left abdomino-thoracic incision, with total gastrectomy and distal esophagectomy, with N1 and N2 lymphadenectomy, splenectomy, and esojejunal intrathoracic anastomosis, with a Roux-en-Y loop, with or without jejunostomy (13 obs.). The immediate post-operative complications were 8 anastomotic leakage, one duodenal stump fistula, one occlusion due to a jejunostoma, and 13 extradigestive complications. There were 5 post-operative deaths. CONCLUSION: Neoplasm of the esophago-gastric junction is lately diagnosed, but whenever is possible, total gastrectomy with distal esophagectomy should be carried out.

Positive axillary sentinel lymph node: is axillary dissection always necessary?

There is considerable interest in foregoing axillary dissection (AD) when the sentinel node (SN) is positive in early breast cancer, particularly when axillary involvement is minimal (micrometastases or isolated tumor cells). In fact, clinical practice has run ahead of the evidence, since recent population-based data indicate that AD is 'underused' in breast cancer patients when the SN is positive. Several trials are addressing the problem (IBCSG 23-01, ASCOG Z0011, EORTC AMAROS). Only Z0011 has published interim results, finding, after a median follow-up of 6.3 years, no differences in locoregional recurrence or regional recurrence between patients, with a positive SN, who received AD vs. no further axillary treatment. Our own retrospective study evaluated patients with micrometastases or isolated tumor cells in the SN who received no further axillary treatment. We found high five-year survival and low cumulative incidence of axillary recurrence, supporting the findings of Z0011 and justifying the increasingly common practice of foregoing AD in women with minimal SN involvement. It is important to sound a note of caution however: If axillary dissection is not always necessary in women with a positive axilla, it seems important to be able to reliably identify the patients at high risk of developing overt axillary disease who should receive elective AD. Ancillary analyses of the IBCSG 23-01 and AMAROS trials, still in follow-up, may be able to do this.

Early recurrence in favorable stage II breast cancer--which approach is the best?

AIM: Changing the sequence of therapeutic options in stage II breast cancer: first, a core biopsy, followed by the evaluation of the tumoral markers, adaptation of the chemotherapy scheme and finally, surgical approach. Thus would be possible to improve the hope of life in some stage II breast cancer patients, in whom survival is poorer than in some stage III patients. MATERIAL AND METHOD: 144 patients in stage II breast cancer were included in this study, over a period of 5 years (2000-2004). In all these patients the first therapeutic option was surgery (radically modified mastectomy type Madden), followed by systemic chemotherapy-FAC or FEC, 6 cycles, and finally Tamoxifen. RESULTS: 34 out of them developed metastases in a period between 6 and 72 months, most of them in the first 26 months; 25 out of these 34 didn't have metastases in the axillary lymph nodes, and in 18 patients estrogen--and progesterone--receptors were highly positive. HER 2 neu was negative or low expressed in patients with metastases. CD 34 wasn't evaluate in the whole group. CONCLUSIONS: Early onset of metastases in the studied patients, in whom tumoral aggressiveness markers were not obvious, impose the evaluation of the angiogenesis markers and, when positive, chemotherapy as the first therapeutic option.

[Frozen section exam value in breast cancer]. / Valoarea examenului histopatologic extemporaneu in cancerul mamar.

Frozen section exam is a peroperative analysis that allows an immediate histopathological diagnosis. Its result influences the extent of surgery. First used only for intraoperative histologic diagnosis, frozen section exam has modified its place nowadays due to the progress in screening methods and preoperative histologic diagnosis. Conservative treatment and sentinel lymph node biopsy technique has orientated frozen section exam towards the evaluation of the sentinel lymph node metastasis and the specimen margins. Sentinel lymph node method remains open to new persectives, influencing therapy decisions, enlarging its indications and improving continuously.

[Internal hernia--a rare cause of intestinal obstruction]. / Hernia interna--o cauza rara de ocluzie intestinala.

Internal hernia is rare its frequency ranging between 0.6 and 5.8%. It results from the protrusion of one or more abdominal viscera (usually small bowel) through an intraperitoneal opening. The opening can be normal (e.g. Winslow foramen), congenital (paraduodenal fossa, ileocecal fossa), or abnormal anatomical entities (after trauma or surgery). The clinical diagnosis of internal hernia is difficult because of the lack of specific signs and symptoms. There is a 63.6% lifetime risk of strangulation and bowel ischemia. In such cases, computed tomography is essential in the preoperative diagnosis because of the high mortality rate (20%) (which justifies its costs).

[Severe peripheral ischemia of rare origin]. / Ischemie severe peripherique d'origine inhabituelle.

The authors describe a rare case of acute peripheral ischemia in a young patient, following a lower limb orthopaedic surgery. The clinical presentation and diagnosis tests suggested a Horton arteritis with peripheral symptoms, although the temporal artery biopsy was negative. Since the etiology was unclear, the authors considered the influence of local trauma (initial and surgical), of Ergot derivatives and antibiotic treatment, but the clinical outcome after corticotherapy strongly indicated a temporal arteritis.

[Bilateral breast cancer (BBC). Considerations on a series of 20 cases]. / Cancerul mamar bilateral consideratii pe un lot de 20 de observatii.

The aim of this study was to assess breast cancer incidence, diagnostic possibilities in clinical treatable stages and the prognosis in a series of breast cancer patients repeatedly treated in the same unit, by the same team. Diagnostic difficulties in the early stage of the contralateral cancer constitute a proven reality even in our cases. The detection of the second metachronous breast tumor was done and evaluated mostly in an more advanced stage than the initial tumours. This might be explained by the delayed visit to the doctor. Most BBC were lobular carcinoma. Adjuvant therapy--chemotherapy, antiestrogens, ovariectomy--do not prevent the appearance of the second tumoral site.

[Different phenotypes generated by changes in bcl-2 and p53 expression in breast cancer]. / Fenotipuri diferite generate prin modificari in expresia bcl-2/p53 in cancerul mamar.

We have identified by immunohistochemistry/ immunocytochemistry the expression of bcl-2 molecule in 55 primary breast carcinomas and in 30 corresponding axillary lymph nodes metastases, together with a set of molecules known as prognostic factors: estrogen receptors, progesterone receptors, and p53 protein. Our results demonstrated a significant correlation (p < 0.05) between bcl-2 and hormonal receptors expression in tumors, but not in axillary metastases (p < 0.1), a significant inverse correlation between bcl-2 and p53 expression in primary tumors (p < 0.02), but a significant direct correlation in axillary metastases (p < 0.02). The bcl-2+/p53- phenotype, associated with normal breast epithelium, is present in 79.17% primary tumors, but only in 15.38% axillary lymph nodes metastases. A larger number of lymph nodes metastases expressed a bcl-2+/ p53+ more aggressive phenotype compared with primary tumors (58.82% versus 48.39%). This shows that changes in the expression of bcl-2, p53, estrogen and progesterone receptors can lead to an increased cellular aggressiveness and thus to an increased tumoral invasive and metastasizing potential.

[High values of soluble cytokeratin 18 in breast carcinomas may have different meanings]. / Valorile crescute ale citokeratinei 18 serice in neoplasmele mamare pot avea semnificatii diferite.

We have investigated the cellular and serum CK18 in 26 non-treated primary ductal invasive breast carcinomas. The soluble CK18 (TPS) was detected by chemiluminescent assay, and the cellular CK18 and PCNA expression by immunocytochemistry. Flow-cytometry was used to estimate the amount of DNA in malignant cells. There was a significant correlation between soluble CK18 and the pre-menopausal status (p < 0.05), characterized in our group by a PCNA estimated low proliferation index. We have also found a significant correlation between soluble CK18 and the DNA index (p < 0.01). The intracellular CK18 has correlated with the PCNA expression (p < 0.05), while no correlation could be found between cellular and serum CK18. The values of soluble CK18 may offer information about the treatment-induced cell death, if monitored, while isolated measurements should be interpreted cautiously. Elevated levels of serum CK18 in non-treated carcinomas may rather reflect a high tumor turn-over or perhaps a more intensive tumor cell killing.

[The link between glomerulonephritis and hydatid disease ]. / Relatia glomerulonefrita boala hidatica.

The presence of glomerular damage was evaluated for 338 patients, adults (298) and children (40), with pulmonary or hepatic hydatid disease. A descriptive study was used. The glomerular syndrome was present in 2 children (5%) with hydatid disease, 22 adults (11%) with liver echinococcosis and 28 adults (18%) with pulmonary echinococcosis. An early stage diagnosis and proper treatment will determine the reversibility of glomerulonephritis.