Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21.4% for NACT versus 15.9% for adjuvant chemotherapy (5.5% increase [95% CI 2.4-8.6]; rate ratio 1.37 [95% CI 1.17-1.61]; p = 0.0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38.2% for NACT vs 38.0% for adjuvant chemotherapy; rate ratio 1.02 [95% CI 0.92-1.14]; p = 0.66), breast cancer mortality (34.4% vs 33.7%; 1.06 [0.95-1.18]; p = 0.31), or death from any cause (40.9% vs 41.2%; 1.04 [0.94-1.15]; p = 0.45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. Copyright (c) The Author(s). Published by Elsevier Ltd.

The aim of this study was to investigate lymph circulation before and after breast reduction mammaplasty in different parts of the breast and with two different carriers of the radiopharmaceutical. Nine patients with breast hypertrophy planned for bilateral breast reduction mammaplasty were prospectively included in the study. The breast operation procedure was decided on intraoperatively. The regional lymph circulation in the breast was measured preoperatively by Technetium (99mTc) clearance in 4 different locations in each breast 1, 2 and 3 hours after injection. The procedure was repeated at one month and in six of the nine women also five years postoperatively with injection sites chosen to correspond to the preoperative location of that breast pedicle. Two different types of carriers of the radiopharmaceutical were tested, dextran in the right and nanocoll in the left breast. Dextran had a much more rapid clearance than nanocoll. There was no significant regional difference in lymph drainage up to five years after the mammaplasty, independent of dextran or nanocoll as being the carrier of the radiopharmaceutical.

Nipple-areola complex (NAC) and skin flap ischemia and necrosis can occur after nipple-sparing mastectomy (NSM). The purpose of this study was to correlate vascular findings on MRI with outcomes in patients who underwent NSM.Female patients at a single institution who underwent NSM and had a preoperative breast MRI between 2010 and 2014 were identified. Medical records were reviewed for patient demographics, surgical factors, and complications. Magnetic resonance images were reviewed by 2 radiologists, blinded to outcomes, for the presence of dual vs single blood supply to the breast. The association between blood supply on MRI with ischemic and necrotic complications after NSM was analyzed.One hundred and sixty-four NSM procedures were performed in 105 patients (mean age 45.5 years, range 25 to 69 years) who had a preoperative MRI. The majority of procedures were performed for malignancy (89 of 164 [54.3%]) or prophylaxis (73 of 164 [44.5%]). Nipple-areola complex or skin flap ischemia or necrosis occurred in 40 (24.4%) breasts. Ischemia or necrosis after NSM was less likely to occur in breasts with dual compared with single blood supply (20.8% vs 38.2%; p = 0.03). There was no association between surgical complications and age, BMI, smoking history, previous radiation therapy, indication for NSM, surgical specimen weight, surgical incision type, reconstruction approach, or operating surgeon on univariate analysis.Preoperative MRI characterization of breast vascularity can be considered when planning NSM. The presence of a dual blood supply to the breast on MRI is associated with a decreased risk of nipple-areola complex and skin flap ischemia and necrosis after NSM.

Purpose: To investigate lymphatic drainage as measured by lymphoscintigraphy in the arms of patients undergoing either sentinel lymph node biopsy (SNB) or axillary lymph node dissection (ALND).Material and Methods: From January 2001 to December 2002, 30 patients with unilateral invasive breast carcinoma underwent breast-conserving surgery with SNB and 30 patients with ALND. All patients received radiotherapy to the breast. Lymphoscintigraphy was performed, and skin circulation, skin temperature, and arm volume were measured 2 - 3 years after radiotherapy.Results: None of the 30 patients who underwent SNB showed any clinical manifestation of lymphedema. Of the 30 patients undergoing ALND, six (20%) had clinical lymphedema, with an arm volume that was > 10% larger on the operated than on the non-operated side ( P < 0.01). Scintigraphically, visual analysis revealed lymphatic dysfunction in three patients, manifested as forearm dermal back flow. Two of these patients also had an increased arm volume. Quantitative analysis showed no differences between the groups, apart from a smaller amount of isotope in the axilla in the ALND group. There was no difference in skin circulation or skin temperature.Conclusion: Our study shows that lymph drainage in the operated arm compared with the non-operated arm was less affected by SNB than by ALND, and that morbidity associated with SNB was lower than with ALND. However, the results do not confirm our hypothesis that lymphoscintigraphy can reveal differences in lymph circulation that are not evident clinically in the form of manifest lymphedema. The most sensitive clinical method of assessing lymph drainage seems to be measurement of arm volume.

AIM:Validation of the oncological safety of nipple-sparing subcutaneous mastectomy and immediate reconstruction with implants (NSM) and of the outcome in patients with locoregional recurrences (LRRs) after this procedure. METHODS:Two-hundred and sixteen patients, mean age of 52.8 (29-81) years with primary unilateral breast cancer, not suitable for partial mastectomy because of large (>3cm) or multifocal carcinoma, underwent NSM, a single procedure lasting about 1h 30min, between December 1988 and September 1994. Lymph node metastases were found in 40.3% of the patients, and 47 patients received radiotherapy (RT) postoperatively. All patients were monitored for at least 11.6 years or as long as they lived. Median follow-up was 13 years. The end-points were locoregional recurrence (LRR) or distant metastases (DM) as first events, disease-free survival (DFS) and overall survival (OS). RESULTS:Specificity at frozen section from sub-areolar tissues was 98.5%. LRR occurred in 52 patients and DM in 44 patients. DFS was 51.3% and OS was 76.4%. The frequency of LRR was 8.5% among irradiated and 28.4% among non-irradiated patients (p=0.025). These results compare well with results after conventional mastectomy in other trials. All patients were monitored for at least 6 years after the occurrence of LRR, finding 5 years freedom from further LRR or DM of 60% and OS of 82%. CONCLUSIONS:NSM is an oncologically safe procedure and could be offered to most patients with breast cancer unsuitable for sector resection only. RT effectively lowers the frequency of LRR. The occurrence of LRR after this operation does not significantly affect OS.

The aim of this study was to compare the sensitivity of intraoperative frozen section with hematoxyllin-eosin (H&E) staining, immunohistochemistry (IHC) or imprint cytology (IC) in the analysis of sentinel node (SN) in breast cancer.Towards this end, a prospective study of 102 patients undergoing mastectomy or sector resection with SN biopsy was conducted. Frozen sections of SN with H&E, IHC staining and IC had sensitivities of 73.5%, 75.5% and 51.0%, respectively. The combination of H&E and IHC raised the overall sensitivity to 83.7%. Macrometastases (>2mm) were detected in 100% of the cases with H&E, 92.6% with IHC and 81.5% with IC; and micrometastases (⩽2mm) in 35.0%, 45.0% and 5.0%, respectively. The combination of H&E and IHC staining raised the sensitivity to 55.0%. Frozen-section analysis with H&E staining showed high sensitivity in detecting macrometastases but not micrometastases. The sensitivity for detection of micrometastases was not substantially increased by the use of intraoperative IHC. Imprint cytology did not provide any additional information.

The aim of this study was to investigate the breast lymph circulation and skin blood circulation after radiotherapy and breast conservation. In 23 patients who had undergone lumpectomy for breast cancer (mean age 58 years, range 44-75) and 12 patients with lumpectomy for benign lesions (mean age 51 years, range 33-72), lymph circulation in the breast was measured by 99mTc-nanocolloid clearance and skin circulation by Laser Doppler Fluxmetry (LDF). Measurements were made 2-5 years after radiotherapy (50 Gy) in the former group and at a corresponding time in the latter. The lymph circulation was measured 2 cm above and medial or lateral to the areolar border in the quadrant not operated on for carcinoma. Skin circulation was measured at corresponding sites. The lymph circulation expressed as the ratio of 99mTc-nanocolloid clearance in the operated irradiated to that in the non-operated (radiation 2-4 Gy) breast was 2.33 (2.66) (median, interquartile range) (p value 0.01) and the skin circulation ratio over the corresponding area was 0.92 (0.21). Corresponding ratios in the non-radiotherapy group were 2.07 (1.96) (p value 0.03) and 1.04 (0.18) respectively. Compared with the control breast (i.e., the non-operated non-irradiated breast), there was a 4-fold increase in lymph flow in the operated, irradiated breast, a 2.5-fold increase in the contralateral non-operated (2-4 Gy) breast and a 1.5-fold increase in the operated non-irradiated breast. Radiotherapy after breast conservation surgery leads to increased long-term changes in basal lymph circulation and smaller increases in lymph flow in the contralateral breast receiving 2-4 Gy and after surgery. If maximal lymph transport capacity is unchanged, edema may be more likely in this circumstance of reduced lymphatic transport reserve.

One hundred and seven breast cancer patients underwent subcutaneous mastectomy and immediate reconstruction with a subcutaneously-placed, round, saline-filled prosthesis with a textured surface. The primary aim of this prospective study was to determine the frequency of capsular contracture in both irradiated and non-irradiated breasts after this operation. Two different types of round implants with different pore sizes on their textured surfaces, Sittex(R) and Microcell(R), were randomly chosen. Twenty-four patients received radiotherapy within the first year following the operation. Capsular contracture was measured by the Baker/Patmer classification and by applanation tonometry at regular intervals for 5 years or as long as the patients lived (median 60 months). Twenty-two patients (20.6%) developed capsular contracture, defined as Baker three or four. Sixteen of those were reoperated, 15 with open capsulotomy with or without implant exchange, one with closed compression capsulotomy, and monitored thereafter for 5 years or until death (median 60 months). All 107 patients could be monitored for 2 years, while 87 reported for the 5-year follow-up. The rate of capsular contracture was significantly higher (p=0.01) for irradiated breasts than for non-irradiated ones, 41.7 and 14.5%, respectively. It was slightly higher (p<0.05) for large-pore implants than for those with smaller (and more numerous) pores. There was a good correlation between the two different methods for measuring capsular contracture. None of the 16 reoperated patients had a recurrence of capsular contracture within 5 years.The results indicate a high rate of capsular contracture after this operation, especially when followed by radiation. However, a fairly simple procedure to treat capsular contracture seems to give good long-term results. (C) 2005 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved.

IM862, manufactured by Cytran Inc, is a bipeptide with antiangiogenctic effects and only minor side effects. The drug is administered as nose drops. The aim of this pilot study was to evaluate the local response of IM862 in patients with locally advanced pancreatic cancer. Ten patients with unresectable pancreatic cancer with an estimated survival of at least 4 months were included. The patients were examined before and every 3 month by CT-scan and MRI and every month by antigene CA 19-9. IM862 5 mg was taken as nose drops 3 times a day. IM862 as a single therapy is not enough to prevent progression of pancreatic cancer. There was a period of stable disease for 6-9 months. In the future a combination of antiangiogenetic therapy and chemotherapy might be beneficial.

Background: Postsurgical adhesion formation is a common occurrence after most surgical procedures and is still a major cause of postoperative morbidity because no satisfactory treatment or prophylaxis has yet been developed. Further elucidation of the basic mechanisms of postsurgical adhesion formation is needed. Recent studies using germfree rats have found the indigenous bowel flora to be important in the adhesive response. The present study examined whether antibiotic treatment affects intra-abdominal adhesion formation. Methods: Using the cecal crush model to inflict adhesions, groups of rats (n=12) were treated with placebo or amoxicillin/clavulanic acid in the drinking water. Treatment started 3 days before operation and continued until evaluation. Adhesion scores were recorded after 7 days. Bacterial counts were made from cultures of fecal samples on operation day and at termination. Results: Amoxicillin/clavulanic acid decreased adhesion score compared to placebo. Adhesion incidence was 50% in the treatment group and 92% in the placebo group. Bacterial numbers were lower in the treatment group. Conclusions: Antibiotic treatment which lowers bacterial numbers can decrease adhesions.

PURPOSE:To evaluate the value of dynamic MR imaging as an adjunctive tool to triple diagnosis (TD) (physical examination, mammography and fine needle aspiration cytology) in diagnosing breast lesions.MATERIAL AND METHODS:Ninety-three consecutive patients with 114 palpable or mammographically detected breast lesions were examined with TD and MR imaging. The MR examination was performed dynamically using a dedicated breast coil. Five diagnostic groups were defined on a scale from 1=normal, to 5 = malignant, where groups 1-3 were defined as benign and groups 4-5 as malignant. All lesions were histopathologically examined. The sensitivity and specificity were calculated for mammography alone, TD, MR and the combination of MR and TD.RESULTS:Histopathology revealed 32 benign and 82 malignant lesions (73 invasive and 9 cancer in situ). The sensitivity/specificity was 84%/59% for mammography, 93%/41% for TD, 94%/47% for MR and 99%/19% for TD + MR. In the 32 mammographically dense breasts, mammography/TD/MR/TD + MR had a sensitivity of 72%/94%/94%/100% and a specificity of 79%/57%/36%/29%, respectively.CONCLUSION:MR imaging might be of value as an additive method to TD by increasing the sensitivity, but at the cost of decreasing specificity. Patients with mammographically dense parenchyma might have more benefit of the additive value, as the decrease in specificity in these patients was less pronounced in our study.

Background: Postsurgical adhesion formation is still a cause of postoperative morbidity because no satisfactory treatment or prophylaxis has yet been developed. The present study was designed to investigate the influence of the gastrointestinal flora on adhesion formation around surgical anastomoses.Methods: Anastomoses were constructed in germfree, conventional, ex-germfree and monocontaminated rats (Escherichia coli X7 and Lactobacillus acidophillus La5), and adhesion formation was recorded.Results: The germfree group had a significantly lower adhesion score than all other groups (P < 0.05) apart from the lactobacillus group, which had a significantly lower score than the conventional group (P < 0.05).Conclusion: The bacterial flora of the gastrointestinal tract enhances adhesion formation around surgical anastomoses.

There are uncertainties if radiotherapy influences the circulation in breast after breast conservative surgery. It was found when measured by 133 Xenon clearance that subcutaneous circulation expressed as the ratio operated irradiated to non-operated non-irradiated breast was 0.88 (0.94) (median, interquartiles range), the glandular circulation 0.93 (0.75) and that the skin circulation ratio measured by laser Doppler fluxmetry was 1.00 (0.37) and 1.00 (0.38) over the corresponding areas. The results indicate that radiotherapy following breast conservative surgery does not lead to long-term changes in basal subcutaneous or skin circulation in the breast.

OBJECTIVE:To investigate the breast circulation after radiotherapy and breast conservation.DESIGN:Open clinical study.SETTING:University hospital, Sweden.SUBJECTS:24 patients with breast cancer (mean age 54 years, range 41-64).INTERVENTIONS:The glandular and the subcutaneous circulation in the breast were measured by Xenon (133Xe) clearance and the skin circulation by laser Doppler fluxmetry (LDF) two to five years after radiotherapy (50 Gy) following lumpectomy. The subcutaneous circulation was measured 2 cm above and medial or lateral to the areolar border and the glandular circulation 2 cm below and medial or lateral to the areolar border in the quadrant not previously operated on for carcinoma. The skin circulation was measured at the corresponding sites.MAIN OUTCOME MEASURES:Circulation in the subcutaneous and glandular tissue measured by 133Xe clearance and in the skin by LDF.RESULTS:The subcutaneous circulation, expressed as the ratio of 133Xe clearance in the operated irradiated: non-operated non-irradiated breast, was 0.88 (0.94) (median, interquartile range) and the glandular circulation 0.93 (0.75). The skin circulation ratios over the corresponding areas were 1.00 (0.37) and 1.00 (0.38), respectively.CONCLUSION:Radiotherapy after breast conservation surgery does not lead to long-term changes in basal glandular, subcutaneous, or skin circulation in the breast.

Purpose: the aim of our prospective study was to evaluate the role of planar scintimammography with 99mTc-MIBI in detecting axillary lymph node metastases in women with primary breast carcinoma. Material and Methods: Fifty-eight patients underwent scintimammography prior to axillary lymph node dissection. Ten minutes after injection of 700 MBq 99mTc-MIBI, two prone lateral projections were obtained, followed by a supine anterior projection. Sixty-one axillae (3 bilateral) were operated upon and the status of the lymph nodes verified with histopathology. the scintigraphic result was compared to the histopathologic findings. Results: A sensitivity of 67% and a specificity of 80% of planar scintimammography in detecting axillary lymph node metastases were achieved. Conclusion: Scintimammography with 99mTc-MIBI is not recommended as a routine method for the detection of axillary lymph node metastases in patients with breast carcinoma.

The skin circulation was measured in 43 breast cancer patients following subcutaneous mastectomy and immediate reconstruction with a prosthesis, at least 1 year after radiotherapy (46 Gy) following surgery (19 patients) or if no radiotherapy was given, at least 1 year postoperatively (24 patients). The skin circulation was measured by laser Doppler fluxmetry (LDF) and fluorescein flowmetry within three areas: 2 cm above the border of the areola, within the nipple-areola complex, and 2 cm below the border of the areola. The results show that there was no reduction in skin circulation. On the contrary LDF and fluorescein flowmetry showed in the operated breast an increased circulation in the nipple-areola complex in the irradiated breast compared with the non-irradiated by 26% and 30%, respectively (P < 0.05). The results indicate that radiotherapy following subcutaneous mastectomy and immediate reconstruction with a prosthesis does not lead to long-term reduction in basal skin circulation in the breast.

We have measured the plantar forefoot skin circulation by the uptake of sodium fluorescein (fluorescein flowmetry), Xe-133 clearance and laser Doppler fluxmetry in 24 healthy subjects and correlated measurements under basal conditions and after provocation by alcohol intake and application of external heat, To assess the change in skin circulation between the initial measurement at rest and the second measurement after provocation, the coefficient of correlation (r) of the fluorescein flowmetry to the fast Slope of the Xe-133 elimination curve was 0.46 (p < 0.05), to the slow slope of the Xe-133 elimination curve 0.66 (p < 0.001) and to laser Doppler fluxmetry 0.86 (p < 0.001), The coefficient of correlation (r) of the fluorescence appearance time to fluorescein flowmetry was 0.65 (p < 0.001), to the fast slope of the Xe-133 elimination curve 0.14 (p = 0.42), to the slow slope of the Xe-133 elimination curve 0.47 (p < 0.05) and to laser Doppler fluxmetry 0.63 (p < 0.001), The uptake of sodium fluorescein as measured by fluorescein fluxmetry correlates well with both Xe-133 clearance and laser Doppler fluxmetry in assessing a change in skin circulation in healthy humans, The fluorescence appearance time also correlates to the slow slope of the Xe-133 elimination curve and to laser Doppler fluxmetry though to a lesser extent.

Purpose: To determine the sensitivity and specificity of X-ray mammography and of MR imaging in 238 consecutively operated breasts, and to correlate the findings to histopathological diagnosis. Material and Methods: Over 15 months, 220 patients scheduled for breast surgery were examined consecutively, before surgery, by means of both mammography and MR imaging. of the 220 patients, 18 underwent bilateral breast surgery. The entire breast was examined by means of T1-weighted transversal images using a 3D fast low-angle shot (FLASH) sequence. One pre— and 2 post-contrast scans were performed. Each breast was examined by means of mammography and 3 views were applied as routine. All palpable and mammographically suspect lesions were examined on additional images as microfocus magnification or spot compression. The two methods were evaluated independently of each other. Results: In total, 145 malignant and 93 benign lesions were found at histopathological examination. The sensitivity of mammography was 89% and MR imaging 92%. The specificity was 72% in both methods. When the results of the 2 methods were combined, a sensitivity of 99% and a specificity of 55% was achieved. Conclusion: Mammography and MR imaging seemed to complement each other to produce a high sensitivity. Unfortunately it is impossible at present to supplement mammography with MR imaging in each patient as a routine owing to the current technical and financial limitations.

BACKGROUND AND OBJECTIVES:Interpleural analgesia is an effective method for pain relief after upper abdominal surgery. To examine whether the analgesic effect is obtained by block of the intercostal nerves, we assessed the analgesic efficacy of the block, the skin sensitivity, and indices of sympathetic outflow over the trunk. METHODS:Interpleural analgesia was instituted at the end of open cholecystectomy in 20 patients 24-81 years of age (mean, 42 years). After a washout period of 8 hours, the analgesic effect was tested 5-12 times during the postoperative follow-up period by using a visual analogue scale before and 20 minutes after injection of 20 mL of bupivacaine 0.25%. Temperature and pain sensations were tested on the day after surgery, and in nine of the patients, the cutaneous blood flow over the trunk was studied by an electronic thermometer, laser Doppler flowmetry, and fluorescein flowmetry. In addition, the conduction velocity in the phrenic nerve was studied in four of the patients. RESULTS:Interpleural analgesia significantly reduced the median visual analogue score from of 5.7 (range 2-10) to 1.1 (range, 0-4). Although the analgesic effect was very good in all patients, half of them still showed skin sensitivity to pain and temperature. Cutaneous blood flow did not change, which showed than block of the intercostal nerves was incomplete. The phrenic nerve was not affected. CONCLUSION:The incomplete cutaneous sensory and sympathetic block indicates that the analgesic effect of interpleural analgesia cannot be explained by retrograde diffusion of the local anesthetic solution into the intercostal nerves alone.