Long-term outcome of COVID-19 patients with acute kidney injury requiring kidney replacement therapy.

BACKGROUND: Limited data existed on the burden of coronavirus disease 2019 (COVID-19) renal complications and the outcomes of the most critical patients who required kidney replacement therapy (KRT) during intensive care unit (ICU) stay. We aimed to describe mortality and renal function at 90 days in patients admitted for COVID-19 and KRT. METHODS: A retrospective cohort study of critically ill patients admitted for COVID-19 and requiring KRT from March 2020 to January 2022 was conducted in an Italian ICU from a tertiary care hospital. Primary outcome was mortality at 90 days and secondary outcome was kidney function at 90 days. RESULTS: A cohort of 45 patients was analyzed. Mortality was 60% during ICU stay and increased from 64% at the time of hospital discharge to 71% at 90 days. Among 90-day survivors, 31% required dialysis, 38% recovered incompletely, and 31% completely recovered renal function. The probability of being alive and dialysis-free at 3 months was 22%. CONCLUSIONS: Critically ill patients with COVID-19 disease requiring KRT during ICU stay had elevated mortality rate at 90 days, with low probability of being alive and dialysis-free at 3 months. However, a non-negligible number of patients completely recovered renal function.

Prophylactic Salpingo-Oophorectomy and Survival After BRCA1/2 Breast Cancer Resection.

Importance: Few studies have investigated whether prophylactic salpingo-oophorectomy (PSO) for patients with previously resected breast cancer who carry pathogenic germline BRCA1 or BRCA2 variants is associated with a reduced risk of cancer-specific death. Objective: To assess the association of PSO and prophylactic mastectomy (PM) with prognosis after quadrantectomy or mastectomy as primary treatment for patients with BRCA1 or BRCA2 breast cancer. Design, Setting, and Participants: This retrospective cohort study was performed in a single-institution, tertiary referral center. Consecutive patients with invasive breast cancer treated surgically between 1972 and 2019 were recruited and followed up prospectively after they were found to carry the BRCA1 or BRCA2 gene variant. The data analysis was performed between April 2022 and July 2023. Exposure: Following breast surgery, some patients underwent PSO, PM, or both, whereas others did not. Main Outcomes and Measures: The primary study end point was overall survival as measured by the Kaplan-Meier method. Secondary end points were crude cumulative incidence of breast cancer-specific mortality, ipsilateral breast tumor recurrence (IBTR), contralateral breast cancer, ovarian cancer, and ovarian cancer-specific mortality. Results: Of 480 patients included in the cohort (median age at initial surgery, 40.0 years; IQR, 34.0-46.0 years), PSO was associated with a significantly reduced risk of death (hazard ratio [HR], 0.40; 95% CI, 0.25-0.64; P < .001). This reduction was most evident for patients carrying the BRCA1 variant (HR, 0.35; 95% CI, 0.20-0.63; P = .001), those with triple-negative disease (HR, 0.21; 95% CI, 0.09-0.46; P = .002), and those with invasive ductal carcinoma (HR, 0.51; 95% CI, 0.31-0.84; P = .008). Prophylactic salpingo-oophorectomy was not associated with risk of contralateral breast cancer or IBTR. Initial or delayed PM was associated with a reduced risk of IBTR but not with overall survival or breast cancer-specific mortality. Conclusions: The study findings suggest that PSO should be offered to all patients with BRCA1/2 breast cancer who undergo surgery with curative intent to reduce risk of death. In particular, PSO should be offered to patients with the BRCA1 variant at the time of breast surgery.

Magnetic Localization of Breast Lesions: A Large-Scale European Evaluation in a National Cancer Institute.

INTRODUCTION: For decades the standard for preoperative breast lesions' localization has been wire localization. In recent years the options for nonwired localization have significantly expanded and include radioactive seeds, radar reflectors, radiofrequency identification tags and magnetic seeds. The aim of our study is to evaluate on a large scale the performance of preoperative magnetic seed localization of nonpalpable breast lesions. MATERIAL AND METHODS: We prospectively collected data on all patients undergoing image-guided magnetic seed localization from September 2019 to December 2022. We analyzed imaging findings, histological results, and type of surgery. The primary outcome was the successful localization rate. Secondary outcomes were the successful placement rate, the ease of percutaneous positioning, the procedural complications, and the reintervention rate. RESULTS: A total of 1123 magnetic seeds were placed in 1084 patients by 4 radiologists under ultrasound (1053) or stereotactic (70) guidance. All seeds were detectable transcutaneously in all breasts sizes and at all depths by 7 surgeons with a success rate of 100%. A total of 97.5% seeds were correctly placed into the target lesions (only 2.5% were dislocated). All radiologists have shown good compliance during the procedure, and there were no complications or safety issues. The reoperation rate was 5.1%. CONCLUSIONS: Image-guided localization with magnetic seeds is an easy, safe, reliable, and effective method for localizing nonpalpable breast lesions. Both radiologists and surgeons agreed that the technology was intuitive to use and that it can be widely applied in preoperative localization in breast units.

Breast cancers arising in subjects with germline BRCA1 or BRCA2 mutations: Different biological and clinical entities with potentially diverse therapeutic opportunities.

Breast cancers (BCs) arising in carriers of germline BRCA1 and BRCA2 pathogenic variants (PVs) have long been considered as indistinguishable biological and clinical entities. However, the loss of function of BRCA1 or BRCA2 proteins has different consequences in terms of tumor cell reliance on estrogen receptor signaling and tumor microenvironment composition. Here, we review accumulating preclinical and clinical data indicating that BRCA1 or BRCA2 inactivation may differentially affect BC sensitivity to standard systemic therapies. Based on a different crosstalk between BRCA1 or BRCA2 and the ER pathway, BRCA2-mutated Hormone Receptor-positive, HER2-negative advanced BC may be less sensitive to endocrine therapy (ET) plus CDK 4/6 inhibitors (CDK 4/6i), whereas BRCA2-mutated triple-negative breast cancer (TNBC) may be especially sensitive to immune checkpoint inhibitors. If validated in future prospective studies, these data may have relevant clinical implications, thus establishing different treatment paths in patients with BRCA1 or BRCA2 PVs.

Echocardiographic assessment of pulmonary capillary wedge pressure by E/e' ratio: A systematic review and meta-analysis.

BACKGROUND: The reliability of echocardiographic methods for the assessment of pulmonary capillary wedge pressure (PCWP) is still a matter of debate. Since its first description, the E/e' ratio has been regarded as a suitable method. The aim of this study is to evaluate the evidence of how E/e' effectively estimates PCWP and its diagnostic accuracy for elevated PCWP. METHODS: We systematically searched MEDLINE and Embase databases for studies investigating the agreement between E/e' and PCWP, from inception to July 2022. We limited our research to studies published from 2010 to date. Retrospective studies and studies on non-adult population were excluded. RESULTS: Twenty-eight studies, involving a total of 1964 subjects, were included. The pooled analysis of the studies showed a modest correlation between E/e' and PCWP. The weighted average correlation (r) is 0.43 (95% CI 0.37-0.48). We found no significant differences between reduced and preserved ejection fraction groups. Thirteen studies analysed the diagnostic accuracy of E/e' for elevated PCWP. The AUC of receiver operating characteristic curves for PCWP >15 mmHg was estimated in the interval 0.6-0.91. DISCUSSION: E/e' appears to have a modest correlation with PCWP and an acceptable accuracy for elevated PCWP. (PROSPERO number, CRD42022333462).

Sentinel Node Biopsy Alone or With Axillary Dissection in Breast Cancer Patients After Primary Chemotherapy: Long-Term Results of a Prospective Interventional Study.

OBJECTIVE: To ascertain, in cN0/1 breast cancer patients given primary chemotherapy followed by sentinel node biopsy (SNB), whether SNB alone is adequate axillary treatment if the sentinel nodes (SNs) are clear (pN0). SUMMARY BACKGROUND DATA: 2020 guidelines do not recommend SNB in most cN1 patients with clear SNs after primary chemotherapy because the high SNB false negative rate might lead to poorer outcomes. METHODS: We prospectively assigned SNB after primary chemotherapy to 353 consecutive cT2 cN0/1 patients, median age 47 years (range 22-76) treated from 2007 to 2015. If the SNs were pN0, patients generally received no further axillary treatment (SNB only); if the SNs were pN1, completion axillary dissection (AD) (SNB + AD) was usually performed. Primary outcomes were overall (OS) and disease-free (DFS) survival in SNB only versus SNB + AD patients, assessed by Kaplan-Meier and compared using log-rank test, with use of propensity scores to account for bias due to nonrandom assignment to SNB versus SNB + AD. RESULTS: Median follow-up was 108 months, interquartile range 66 to 136. OS and DFS did not differ significantly between the groups by propensity score- weighted comparison: 10-year OS 89% [95% confidence interval (CI): 81%- 99%] in SNB only patients versus 86% (95%CI: 78%-95%) in SNB + AD patients; 10-year DFS 79% (95%CI: 68%-92%) versus 69% (95%CI: 58%-81%). No SNB-only patient developed axillary failure. CONCLUSIONS: cT2 cN0/1 patients whose SNs are disease-free (pN0) after primary chemotherapy can be offered SNB (with no further axillary treatment if the SNs are negative), irrespective of axillary status beforehand, without affecting OS or DFS.

Right Heart Thrombus in an Adult COVID-19 Patient: A Case Report.

INTRODUCTION: Right heart thrombus (RiHTh) can be considered a rare and severe condition associated with thromboembolic phenomena. A case is described of a COVID-19 patient presenting with an isolated thrombus in the right ventricle. CASE PRESENTATION: An 80-years-old Caucasian male was admitted in an intensive care unit (ICU) for COVID-19 related acute respiratory distress syndrome. The patient showed signs of hemodynamic instability, elevated cardiac troponin I and altered coagulation. On further assessment, a thrombotic mass near the apex of the right ventricle was detected. Moreover, the apex and the anteroseptal wall of the right ventricle appeared akinetic. Following the administration of a therapeutic dose of unfractionated heparin over a forty-eight hour period, re-evaluation of the right chambers showed that the thrombotic mass had resolved entirely. CONCLUSION: COVID-19 patients could constitute a population at risk of RiHTh. Routine use of echocardiography and a multidisciplinary approach can improve the management of this condition.

Red clover and lifestyle changes to contrast menopausal symptoms in premenopausal patients with hormone-sensitive breast cancer receiving tamoxifen.

PURPOSE: To determine whether a red clover preparation plus dietary intervention administered to premenopausal women with breast cancer (BC), improves menopausal symptoms due to anti-oestrogen treatment, and hence promotes compliance with tamoxifen, prevents weight gain and is safe. METHODS: Surgically-treated premenopausal women with oestrogen receptor (ER) positive disease taking tamoxifen were recruited to a prospective double-blind randomized trial (NCT03844685). The red clover group (N = 42) received one oral tablet/day (Promensil® Forte) containing 80 mg red clover extract for 24 months. The placebo group (N = 39) received one oral tablet/day without active ingredient. All women were encouraged to follow a Mediterranean-type diet and keep active. Outcomes were Menopausal Rating Score (MRS), body mass index (BMI), waist and hip girth, insulin resistance, and levels of cholesterol, triglycerides, and sex hormones. As safety indicators, endometrial thickness, breast density, and effects of patient serum on ER-positive BC cell lines were investigated. RESULTS: MRS reduced significantly (p < 0.0001) with no between-group difference (p = 0.69). The red clover group had significantly greater reductions in BMI and waist circumference (p < 0.0001 both cases). HDL cholesterol increased significantly in both groups (p = 0.01). Hormone levels and insulin resistance changed little. Endometrial thickness remained constant (p = 0.93). Breast density decreased significantly in both groups (p < 0.0001). Proliferation and oestrogen-regulated gene expression didn't differ in cell lines treated with serum from each group. CONCLUSIONS: This is the first trial to assess red clover in BC patients on tamoxifen. The preparation proved safe clinically and in vitro, and was associated with reduced BMI and waist circumference, but the diet-lifestyle intervention probably improved the menopausal symptoms.

Dual effects of leptin in perioperative gas exchange of morbidly obese patients.

Leptin has shown positive effects on respiratory function in experimental settings. The role of leptin on perioperative respiratory function in morbidly obese patients has not been established. We performed a retrospective analysis of morbidly obese patients undergoing laparoscopic sleeve gastrectomy. Fasting serum leptin and interleukin (IL)-6 were measured preoperatively, and arterial blood gases were obtained pre- and postoperatively. Outcome variables were arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and differences in PaO2 and PaCO2 between pre- and postoperative values (ΔPaO2, ΔPaCO2; postoperative minus preoperative). Patients with lower (<40 µg/L) and higher (≥40 µg/L) leptin levels were compared. Bravais-Pearson's correlation, multiple linear regression, and logistic regression analysis were performed. A total of 112 morbidly obese patients were included. Serum leptin was significantly higher in females than in males (42.86±12.89 vs. 30.67±13.39 µg/L, p<0.0001). Leptin was positively correlated with body mass index (r = 0.238; p = 0.011), IL-6 (r = 0.473; p<0.0001), and ΔPaO2 (r = 0.312; p = 0.0008). Leptin was negatively correlated with preoperative PaO2 (r = -0.199; p = 0.035). Preoperative PaO2 was lower, ΔPaCO2 was smaller, and ΔPaO2 was greater in the high leptin group than in the low leptin group. In multiple regression analysis, leptin was negatively associated with preoperative PaO2 (estimate coefficient = -0.147; p = 0.023). In logistic regression analysis, leptin was associated with improved ΔPaO2 (odds ratio [OR] = 1.104; p = 0.0138) and ΔPaCO2 (OR = 0.968; p = 0.0334). Leptin appears to have dual effects related to perioperative gas exchange in obese patients undergoing bariatric surgery. It is associated with worse preoperative oxygenation but improved respiratory function after surgery.

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.

Omission of radiotherapy in elderly patients with early breast cancer: 15-Year results of a prospective non-randomised trial.

BACKGROUND: Whether radiotherapy (RT) is beneficial in elderly (⩾ 70 years) patients undergoing conservative surgery for early breast cancer has long been controversial. Recent randomised trials show that most elderly patients do not benefit from RT. We started a prospective non-randomised trial to address this issue in 1987 and now present results for the 627 consecutive pT1/2cN0 patients recruited, and treated by conservative surgery (quadrantectomy) and tamoxifen, and assigned non-randomly to RT or no RT. METHODS: We used multivariate competing risks models to estimate 15-crude cumulative incidence (CCI) of ipsilateral breast tumour recurrence (IBTR), distant metastasis and breast cancer mortality. The models incorporated a propensity score as a measure of probability of receiving RT based on baseline characteristics, to account for the lack of randomisation. RESULTS: For pT1 patients, 15-year CCIs of IBTR, distant metastasis and breast cancer death were indistinguishable in the RT and no RT groups. For pT2 patients, 15-year CCI of IBTR was much higher in those not given RT (14.6% versus 0.8%, p = 0.004), although breast cancer mortality and distant metastasis did not differ significantly between RT and no RT. CONCLUSIONS: Consistent with the findings of recent randomised trials, our long-term data indicate that most elderly, ER-positive patients with pT1 cN0 breast cancer treated by quadrantectomy do not benefit from RT. The 14.6% CCI of IBTR in our pT2 patients is an additional finding not presented in the trials and suggests that RT should be administered to elderly patients with pT2 disease.

¹8F-FLT PET/CT as an imaging tool for early prediction of pathological response in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy: a pilot study.

PURPOSE: We evaluated whether (18)F-3'-deoxy-3'-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT). METHODS: In this prospective cohort study of 15 patients with locally advanced operable breast cancer, FLT PET evaluations were performed before NCT, after the first cycle of NCT, and at the end of NCT. All patients subsequently underwent surgery. Variables from FLT PET examinations were correlated with postoperative histopathological results. RESULTS: At baseline, median of maximum standardized uptake values (SUVmax) in the groups showing a complete pathological response (pCR) + residual cancer burden (RCB) I, RCB II or RCB III did not differ significantly for the primary tumour (5.0 vs. 2.9 vs. 8.9, p = 0.293) or for axillary nodes (7.9 vs. 1.6 vs. 7.0, p = 0.363), whereas the Spearman correlation between SUVmax and Ki67 proliferation rate index was significant (r = 0.69, p < 0.001). Analysis of the relative percentage change of SUVmaxin the primary tumour (∆SUVTmax(t1)) and axillary nodes (∆SUVNmax(t1)) after the first NCT cycle showed that the power of ∆SUVTmax(t 1) to predict pCR + RCB I responses (AUC = 0.91, p < 0.001) was statistically significant, whereas ∆SUVNmax(t1) had a moderate ability (AUC = 0.77, p = 0.119) to separate subjects with ΔSUVTmax(t1) > -52.9 % into two groups: RCB III patients and a heterogeneous group that included RCB I and RCB II patients. A predictive score µ based on ΔSUVTmax(t1) and ΔSUVNmax(t1) parameters is proposed. CONCLUSION: The preliminary findings of the present study suggest the potential utility of FLT PET scans for early monitoring of response to NCT and to formulate a therapeutic strategy consistent with the estimated efficacy of NCT. However, these results in a small patient population need to be validated in a larger independent cohort.

Is breast cancer curable: a study of long-term crude cumulative incidence.

AIMS AND BACKGROUND: The problem of the search for a proportion of cured patients of breast cancer and the relative time to cure breast cancer has been known since the 1950s. The literature on this topic has developed during the last decades thanks to the availability of studies with long follow-up times, which was required by the type of disease in question. The aim of this study is to estimate, if it exists, the proportion of cured breast cancer patients with a parametric method accounting for competing causes of death. METHODS: In this work we used data from a two-group randomized controlled trial. From 1973 to 1980, 701 women were recruited with breast cancer measuring no more than 2 cm in diameter. They were randomly assigned to radical mastectomy (349 patients) or breast-conserving surgery followed by radiotherapy to the ipsilateral mammary tissue (352 patients). Thanks to a reliable classification of the causes of death, it was possible to analyze data using cause-specific mortality. RESULTS: The parametric crude cumulative incidence estimates by the Gompertz distribution accorded closely with the non-parametric estimates. The analysis was also performed for subsets of patients based on menopausal status and number of positive lymph nodes. Statistical evidence for the existence of a cure fraction ranging from 0.48 to 0.71, depending on the subset, was found. However, the estimated proportion of cured patients has not been reached after 30 years' follow-up for most of the subsets. CONCLUSIONS: Although statistical evidence has been found for the presence of a cure fraction, in practical terms it seems that 30 years after a breast cancer diagnosis cure cannot yet be claimed.

Different biological and prognostic breast cancer populations identified by FDG-PET in sentinel node-positive patients: results and clinical implications after eight-years follow-up.

BACKGROUND: Sentinel node (SN) biopsy is the standard method to evaluate axillary node involvement in breast cancer (BC). Positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (FDG-PET) provides a non-invasive tool to evaluate regional nodes in BC in a metabolic-dependent, biomolecular-related way. In 1999, we initiated a prospective non-randomized study to compare these two methods and to test the hypothesis that FDG-PET results reflect biomolecular characteristics of the primary tumor, thereby yielding valuable prognostic information. PATIENTS AND METHODS: A total of 145 cT1N0 BC patients, aged 24-70 years, underwent FDG-PET and lymphoscintigraphy before surgery. SN biopsy was followed in all cases by complete axillary dissection. Pathologic evaluation in tissue sections for involvement of the SN and other non-SN nodes served as the basis of the comparison between FDG-PET imaging and SN biopsy. RESULTS: FDG-PET and SN biopsy sensitivity was 72.6% and 88.7%, respectively, and negative predictive values were 80.5% and 92.2%, respectively. A subgroup of more aggressive tumors (ER-GIII, Her2+) was found mainly in the FDG-PET true-positive (FDG-PET+) patients, whereas LuminalA, Mib1 low-rate BCs were significantly undetected (p = 0.009) in FDG-PET false-negative (FDG-PET-) patients. Kaplan-Meier survival estimates after a median follow-up of more than 8 years showed significantly worse overall survival for FDG-PET+ patients in node-positive (N+) patients (p = 0.035) as compared to N+/FDG-PET- patients, which overlapped with survival curves of N- and FDG-PET+ or - patients. CONCLUSIONS: Our findings suggest that FDG-PET results reflect intrinsic biologic features of primary BC tumors and have prognostic value with respect to nodal metastases. FDG-PET false negative cases appear to identify less aggressive indolent metastases. The possibility to identify a subgroup of N+ BC patients with an outcome comparable with N- BC patients could reduce the surgical and adjuvant therapeutic intervention.

Axillary lymph node dissection versus no dissection in patients with T1N0 breast cancer: a randomized clinical trial (INT09/98).

BACKGROUND: Although axillary surgery is still considered to be a fundamental part of the management of early breast cancer, it may no longer be necessary either as treatment or as a guide to adjuvant treatment. The authors conducted a single-center randomized trial (INT09/98) to determine the impact of avoiding axillary surgery in patients with T1N0 breast cancer and planning chemotherapy based on biological factors of the primary tumor on long-term disease control. METHODS: From June 1998 to June 2003, 565 patients aged 30 years to 65 years with T1N0 breast cancer were randomized to either quadrantectomy with (QUAD) or without (QU) axillary lymph node dissection; a total of 517 patients finally were evaluated. All patients received radiotherapy to the residual breast only. Chemotherapy for patients in the QUAD treatment arm was determined based on lymph node status, estrogen receptor status, and tumor grade. Chemotherapy for patients in the QU treatment arm was based on estrogen receptor status, tumor grade, and human epidermal growth factor receptor 2 and laminin receptor status. Overall survival (OS) was the primary endpoint. Disease-free survival (DFS) and rate and time of axillary lymph node recurrence in the QU treatment arm were the secondary endpoints. RESULTS: After a median follow-up of >10 years, the estimated adjusted hazards ratio of the QUAD versus QU treatment arms for OS was 1.09 (95% confidence interval, 0.59-2.00; P = .783) and was 1.04 (95% confidence interval, 0.56-1.94; P = .898) for DFS. Of the 245 patients in the QU treatment arm, 22 (9.0%) experienced axillary lymph node recurrence. The median time to axillary lymph node recurrence from breast surgery was 30.0 months (interquartile range, 24.2 months-73.4 months). CONCLUSIONS: Patients with T1N0 breast cancer did not appear to benefit in terms of DFS and OS from immediate axillary lymph node dissection in the current randomized trial. The biological characteristics of the primary tumor appear adequate for guiding adjuvant treatment.

Ex vivo MRI evaluation of breast tumors: a novel tool for verifying resection of nonpalpable only MRI detected lesions.

A fundamental question in surgery of only magnetic resonance imaging (MRI)-detected breast lesions is to ensure their removal when they are not palpable by clinical examination and surgical exploration. This is especially relevant in the case of small tumors, carcinoma in situ or lobular carcinoma. Thirty-nine patients were enrolled in the study, 21 patients with breast lesions detected by both conventional imaging and breast MRI (bMRI) and 18 patients with bMRI findings only. Preoperative bMRI allowed staging the disease and localizing the lesion. In the operating theater, contrast medium was injected 1 minute before skin incision. After removal, surgical specimens were submitted to ex vivo MRI, performed using a dedicated surface coil and Spair inversion recovery sequences for suppression of fat signal intensity. All MRI enhancing lesions were completely included within the surgical specimen and visualized by ex vivo MRI. In the first 21 patients, bMRI was able to visualize branching margins or satellite nodules around the core lesion, and allowed for better staging of the surrounding in situ carcinoma; in the last 18 patients, eight of whom were breast cancer type 1 susceptibility protein (BRCA) mutation carriers, bMRI identified 12 malignant tumors, otherwise undetectable, that were all visualized by ex vivo MRI. This is the first description of a procedure that re-enhances breast lesions within a surgical specimen, demonstrating the surgical removal of nonpalpable breast lesions diagnosed only with bMRI. This new strategy reproduces the morphology and the entire extension of the primary lesion on the specimen, with potentially better local surgical control, reducing additional unplanned surgery.

Cell proliferation of the primary tumor predicts ipsilateral axillary node disease in elderly breast cancer patients.

The present study investigated whether tumor markers such as cell proliferation and steroid receptor status, which have been shown to have relevance for important endpoints (relapse-free and overall survival), can also predict axillary disease in elderly patients with breast cancer. We evaluated 351 consecutive elderly women with breast cancer ≥70 years of age with estrogen receptor (ER)­positive tumors with no palpable axillary nodes, for whom information on cell proliferation determined by the 3H-thymidine labeling index (TLI) and progesterone receptor (PgR) was available. Patients underwent quadrantectomy (70.1%) or quadrantectomy plus radiotherapy (29.9%) without axillary node dissection, followed by adjuvant tamoxifen for at least 2 years. Univariable (cumulative incidence curves) and multivariable analyses (Fine and Gray models) were carried out. After a median follow-up of 16 years, ipsilateral axillary relapse was not related to PgR status but was strongly associated with tumor cell proliferation in both small (pT1) and large (pT2-4b) tumors. Axillary relapse cumulative incidence increased from 1% in patients with low-TLI (≤3%), PgR-positive and pT1 tumors to a maximum of 20% in patients with high-TLI, PgR-negative and pT2-4b tumors. Tumor cell proliferation, determined by TLI at primary surgery, is an important predictor of axillary relapse in elderly ER-positive breast cancer patients and could help to identify patients who should undergo axillary surgery.