Optimizing surgical strategy in locally advanced breast cancer: a comparative analysis between preoperative MRI and postoperative pathology after neoadjuvant chemotherapy.

PURPOSE: In the treatment of breast cancer, neo-adjuvant chemotherapy is often used as systemic treatment followed by tumor excision. In this context, planning the operation with regard to excision margins relies on tumor size measured by MRI. The actual tumor size can be determined through pathologic evaluation. The aim of this study is to investigate the correlation and agreement between pre-operative MRI and postoperative pathological evaluation. METHODS: One hundred and ninety-three breast cancer patients that underwent neo-adjuvant chemotherapy and subsequent breast surgery were retrospectively included between January 2013 and July 2016. Preoperative tumor diameters determined with MRI were compared with postoperative tumor diameters determined by pathological analysis. Spearman correlation and Bland-Altman agreement methods were used. Results were subjected to subgroup analysis based on histological subtype (ER, HER2, ductal, lobular). RESULTS: The correlation between tumor size at MRI and pathology was 0.63 for the whole group, 0.39 for subtype ER + /HER2-, 0.51 for ER + /HER2 + , 0.63 for ER-/HER2 +, and 0.85 for ER-/HER2-. The mean difference and limits of agreement (LoA) between tumor size measured MRI vs. pathological assessment was 4.6 mm (LoA -27.0-36.3 mm, n = 195). Mean differences and LoA for subtype ER + /HER2- was 7.6 mm (LoA -31.3-46.5 mm, n = 100), for ER + /HER2 + 0.9 mm (LoA -8.5-10.2 mm, n = 33), for ER-/HER2+ -1.2 mm (LoA -5.1-7.5 mm, n = 21), and for ER-/HER- -0.4 mm (LoA -8.6-7.7 mm, n = 41). CONCLUSION: HER2 + and ER-/HER2- tumor subtypes showed clear correlation and agreement between preoperative MRI and postoperative pathological assessment of tumor size. This suggests that MRI evaluation could be a suitable predictor to guide the surgical approach. Conversely, correlation and agreement for ER + /HER2- and lobular tumors was poor, evidenced by a difference in tumor size of up to 5 cm. Hence, we demonstrate that histological tumor subtype should be taken into account when planning breast conserving surgery after NAC.

[A cachectic man with a severe vitamin deficiency]. / Een cachectische man met een ernstig vitaminetekort.

A 57-year-old man, known with severe malnutrition, vitamin E deficiency and peripheral neuropathies, presented with vomiting and abdominal tenderness. There was a suspicion of ileus and small bowel obstruction. During the exploratory laparotomy a complete brown colored bowel without peristalsis was seen.

Clinical impact of breast MRI with regard to axillary reverse mapping in clinically node positive breast cancer patients following neo-adjuvant chemotherapy.

BACKGROUND: Axillary reverse mapping (ARM) is a technique that discerns axillary lymphatic drainage of the arm from the breast. In the current study, we retrospectively evaluated the incidence of metastatic axillary lymph node involvement, including ARM lymph nodes, in clinically node positive breast cancer patients (cN+ patients) in whom neo-adjuvant chemotherapy (NAC) was administered followed by primary ALND using breast MRI. PATIENTS AND METHODS: Data from 98 cN+ breast cancer patients were analysed retrospectively. Patients without residual axillary disease at breast MRI following NAC (RAD-, n = 64) were compared with patients with residual axillary disease (RAD+, n = 34). Presence of suspect axillary lymph nodes on pre-NAC and post-NAC breast MRI was determined by experienced breast radiologists and was correlated to histopathological findings. RESULTS: In the RAD-group residual axillary disease on pathological analysis following NAC was found in 25 patients (39.1%), as compared to 24 patients (70.6%) in the RAD + group (p = 0.003). Metastatic involvement of ARM lymph nodes following NAC was demonstrated in 5 patients (7.8%) in the RAD-group as compared to 10 patients (29.4%) in the RAD + group (p = 0.005). CONCLUSION: Breast MRI following NAC is not suitable to detect residual metastatic disease of the axilla. However, breast MRI post-NAC may be of use to identify cN+ patients with a low risk of ARM lymph node metastases. This may help to select a subgroup of cN+ patients in whom sparing of ARM lymph nodes during axillary lymph node dissection can be considered.

Two decades of axillary management in breast cancer.

BACKGROUND: Axillary lymph node dissection (ALND) in patients with breast cancer provides prognostic information. For many years, positive nodes were the most important indication for adjuvant systemic therapy. It was also believed that regional control could not be achieved without axillary clearance in a positive axilla. However, during the past 20 years the treatment and staging of the axilla has undergone many changes. This large population-based study was conducted in the south-east of the Netherlands to evaluate the changing patterns of care regarding the axilla, including the introduction of sentinel lymph node biopsy (SLNB) in the late 1990s, implementation of the results of the American College of Surgeons Oncology Group Z0011 study, and the initial effects of the European Organization for Research and Treatment of Cancer AMAROS study. METHODS: Data from the population-based Eindhoven Cancer Registry of all women diagnosed with invasive breast cancer in the south of the Netherlands between January 1993 and July 2014 were used. RESULTS: The proportion of 34,037 women staged by SLNB without completion ALND increased from 0 per cent in 1993-1994 to 69·0 per cent in 2013-2014. In the same period the proportion undergoing ALND decreased from 88·8 to 18·7 per cent. Among women with one to three positive lymph nodes, the proportion undergoing SLNB alone increased from 10·6 per cent in 2011-2012 to 37·6 per cent in 2013-2014. CONCLUSION: This population-based study demonstrated the radical transformation in management of the axilla since the introduction of SLNB and following the recent publication of trials on management of the axilla with a low metastatic burden.

Iodine seed- versus wire-guided localization in breast-conserving surgery for non-palpable ductal carcinoma in situ.

BACKGROUND: Breast-conserving surgery for isolated non-palpable ductal carcinoma in situ (DCIS) is associated with high rates of incomplete surgical resection in comparison with unifocal invasive breast cancer. Therefore, accurate preoperative localization of the lesion is very important to facilitate adequate resection. Wire-guided localization (WGL) remains the standard for localization of DCIS. Recently, iodine-125 seed-guided localization (I-125 GL) was introduced as an alternative localization technique. The aim of this study was to compare the efficacy of these localization techniques in the resection of DCIS by breast-conserving surgery. METHODS: Between March 2006 and June 2013, 169 patients with non-palpable DCIS were treated with breast-conserving surgery. Only patients with pure DCIS on both preoperative core biopsy and definitive pathology were included. RESULTS: WGL was performed in 78 patients and I-125 GL in 91 patients. The groups did not differ with respect to age, size of DCIS or type of imaging used. Patients in the I-125 GL group had a significantly lower risk of extensively involved resection margins than those in the WGL group (4 versus 13 per cent respectively; P = 0·048). CONCLUSION: In patients treated with breast-conserving surgery for non-palpable DCIS, localization with iodine-125 seeds is superior to the WGL technique in reducing the risk of extensively involved resection margins.

Axillary reverse mapping (ARM) in clinically node positive breast cancer patients.

BACKGROUND: Axillary reverse mapping (ARM) is a technique to map and preserve upper extremity lymphatic drainage during axillary lymph node dissection (ALND) in breast cancer patients. We prospectively evaluated the metastatic involvement of ARM-nodes in patients who underwent an ALND for clinically node positive disease following (neo)adjuvant chemotherapy (NAC) in comparison to patients in whom primary ALND was performed without NAC. PATIENTS AND METHODS: Patients with clinically node positive invasive breast cancer, confirmed by fine needle aspiration cytology and scheduled for primary ALND were enrolled in the study. Patients were separated into two groups: one group treated with NAC (NAC+ group) and one group not treated with NAC (NAC- group). ARM was performed in all patients by injecting blue dye into the ipsilateral upper extremity. During ALND, ARM-nodes were first identified and removed separately, followed by a standard ALND. RESULTS: 91 patients were included in the NAC+ and 21 patients in the NAC- group. There was no difference in the ARM visualization rate between the two groups (86.8% for NAC+ group versus 90.5% for NAC- group, P = 0.647). In the NAC+ group 16.5% of the patients had metastatic involvement of the ARM-nodes versus 36.8% of the patients in the NAC- group (P = 0.048). CONCLUSION: The risk of metastatic involvement of ARM-nodes in clinically node positive breast cancer patients is significantly lower in patients who have received NAC.

Relative risks of transformation products of pesticides for aquatic ecosystems.

In this study, the availability of physico-chemical and ecotoxicological information on 78 transformation products for 20 regularly used pesticides in the open literature is evaluated. Based on this information, it is attempted to predict the relative risk for the aquatic environment of each transformation product in comparison to its parent pesticide. It is concluded that for the 78 transformation products selected, the data set on physico-chemical and ecotoxicological behaviour is not very large. Measured log Kow values and other physico-chemical properties are known for only 30-40% of the selected transformation products. The overall reliability of the collected physico-chemical values is considered to be moderate to slight, while for the ecotoxicological data set, reliability is considered to be sufficient. In many cases, there is a need for more information especially on the persistency and no-observed-effect concentrations of the pesticide's transformation products. In general, over 50% of the transformation products of triazines, carbamates and phenoxypropionic acids pose, in theory, a similar to higher risk than their parent pesticide, while over 50% of the transformation products of synthetic pyrethroids, organophosporous pesticides and dithiocarbamates probably pose less risk. High risk was expected for products with high accumulation or persistency in sediment and/or high toxicity together with considerable bioaccumulation (potential) or relatively high concentrations or persistency in water. A generalization of the joint features that caused an increased risk for ecosystems could not be made for most pesticide classes. Exceptions are the synthetic pyrethroids, for which transformation products with a similar or even higher log Kow than the parent pesticide caused an increased potential risk, while for the carbamates the presence of the carbamate group in the transformation product was the joint characteristic of chemicals with predicted increased risk. For three transformation products, monitoring data based on concentrations measured in surface water in The Netherlands were compared with maximum permissible concentrations. This comparison indicated that two of these compounds pose a potential risk of adverse effects in the field situation in Dutch aquatic ecosystems. For all other transformation products, the potential risk in the field situation could not be established because of the absence of monitoring data.

Microbiological aspects of heat sterilization of drugs. III. Heat resistance of spore-forming bacteria, isolated from large-volume parenterals.

In order to calculate the minimum sterilization process conditions to obtain the generally accepted sterility level (less than 1.10(-6) probability of microbial survival), we determined the bioburden and its heat resistance of 500 ml large-volume parenteral bottles over a period of 5 years. For the bioburden determination 1,832 bottles were examined by the membrane filtration method. Mean bioburden was 9.36 colony-forming units/bottle. Of the colony-forming units isolated 118 were heat resistant (0.69%). These were spore-forming Bacillus species. Of the isolated Bacillus species heat resistance was determined in 5% glucose, 0.9% sodium chloride and 8% amino acids solution. D values greater than 1 min at 105 degrees C were found for 2, 5 and 4 different Bacillus species in glucose 5%, sodium chloride 0.9% and amino acids 8%, respectively. 2 Bacillus species showed a D value over 2 min at 105 degrees C in all three media. D values at 110 degrees C in sodium chloride 0.9% for these 2 Bacillus species were 1.8 and 2.6 min and in amino acids 8% 0.9 and 1.7 min, respectively. The minimum sterilization process time at 110 degrees C, calculated with the experimentally determined bioburden and D values is less than 25 min. When introducing reduced exposure times/temperatures, each individual manufacturer should assess the bioburden. The time-consuming determination of the heat resistance of bioburden isolates is not always necessary. By dividing the isolated colony-forming units in a 'heat-resistant' group and a 'not-heat-resistant' group, changing from standard overkill sterilization procedures to processes with lower F0 values is possible.