Impact of preoperative breast MRI on 10-year survival of patients included in the Swedish randomized multicentre POMB trial.

BACKGROUND: The value of preoperative breast MRI as an adjunct technique regarding its effect on re-excision rates has been a subject of discussion. No survival data regarding preoperative breast MRI are available from randomized studies. METHODS: Ten-year follow-up of the POMB randomized multicentre study was analysed, evaluating MRI and its effect on disease-free survival (DFS) and overall survival (OS). Patients with newly diagnosed breast cancer were randomized to either preoperative MRI or conventional imaging. Kaplan-Meier plots were used to analyse DFS and OS, and Cox regression to estimate hazard ratios (HRs). RESULTS: A total of 440 patients, aged 56 years or less, with newly diagnosed breast cancer were randomized to either preoperative MRI (220) or conventional imaging (220; control). Median follow-up for each group was 10 years. DFS rates were 85.5 and 80.0 per cent for the MRI and control groups respectively (P = 0.099). The risk of relapse or death was 46 per cent higher in the control group (HR 1.46, 95 per cent c.i. 0.93 to 2.29). OS rates after 10 years were 90.9 and 88.6 per cent in the MRI and control groups respectively (P = 0.427). The risk of death was 27 per cent higher in the control group (HR 1.27, 0.71 to 2.29). Locoregional, distant, and contralateral recurrence outcomes combined were increased in the control group (P = 0.048). A subgroup analysis of patients with breast cancer stages I-III showed that preoperative MRI improved DFS compared with conventional imaging, but this did not reach statistical significance (P = 0.057). CONCLUSION: After 10 years of follow-up, preoperative breast MRI as an adjunct to conventional imaging resulted in slightly, but non-significantly, improved DFS and OS. Registration number: NCT01859936 (http://www.clinicaltrials.gov).

Omitting completion axillary lymph node dissection after detection of sentinel node micrometastases in breast cancer: first results from the prospective SENOMIC trial.

BACKGROUND: Completion axillary lymph node dissection has been abandoned widely among patients with breast cancer and sentinel lymph node micrometastases, based on evidence from prospective RCTs. Inclusion in these trials has been subject to selection bias, with patients undergoing mastectomy being under-represented. The aim of the SENOMIC (omission of axillary lymph node dissection in SENtinel NOde MICrometases) trial was to confirm the safety of omission of axillary lymph node dissection in patients with breast cancer and sentinel lymph node micrometastases, and including patients undergoing mastectomy. METHODS: The prospective SENOMIC multicentre cohort trial enrolled patients with breast cancer and sentinel lymph node micrometastases who had breast-conserving surgery or mastectomy at one of 23 Swedish hospitals between October 2013 and March 2017. No completion axillary lymph node dissection was performed. The primary endpoint was event-free survival, with a trial accrual target of 452 patients. Survival proportions were based on Kaplan-Meier survival estimates. RESULTS: The trial included 566 patients. Median follow-up was 38 (range 7-67) months. The 3-year event-free survival rate was 96.2 per cent, based on 26 reported breast cancer recurrences, including five isolated axillary recurrences. The unadjusted 3-year event-free survival rate was higher than anticipated, but differed between patients who had mastectomy and those who underwent breast-conserving surgery (93.8 versus 97.8 per cent respectively; P = 0.011). Patients who underwent mastectomy had significantly worse tumour characteristics. On univariable Cox proportional hazards regression analysis, patients who had mastectomy without adjuvant radiotherapy had a significantly higher risk of recurrence than those who underwent breast-conserving surgery (hazard ratio 2.91, 95 per cent c.i. 1.25 to 6.75). CONCLUSION: After 3 years, event-free survival was excellent in patients with breast cancer and sentinel node micrometastases despite omission of axillary lymph node dissection. Long-term follow-up and continued enrolment of patients having mastectomy, especially those not receiving adjuvant radiotherapy, are of utmost importance.

Do clinical trials truly mirror their target population? An external validity analysis of national register versus trial data from the Swedish prospective SENOMIC trial on sentinel node micrometastases in breast cancer.

PURPOSE: Increasing evidence suggests that completion axillary lymph node dissection (ALND) may be omitted in breast cancer patients with limited axillary nodal metastases. However, the representativeness of trial participants for the original clinical practice population, and thus, the generalizability of published trials have been questioned. We propose the use of background data from national registers as a means to assess whether trial participants mirror their target population and to strengthen the generalizability and implementation of trial outcomes. METHODS: The Swedish prospective SENOMIC trial, omitting a completion ALND in breast cancer patients with sentinel lymph node micrometastases, reached full target accrual in 2017. To assess the generalizability of trial results for the target population, a comparative analysis of trial participants versus cases reported to the Swedish National Breast Cancer Register (NKBC) was performed. RESULTS: Comparing 548 trial participants and 1070 NKBC cases, there were no significant differences in age, tumor characteristics, breast surgery, or adjuvant treatment. Only the mean number of sentinel lymph nodes with micrometastasis per individual was lower in trial participants than in register cases (1.06 vs. 1.09, p = 0.037). CONCLUSIONS: Patients included in the SENOMIC trial are acceptably representative of the Swedish breast cancer target population. There were some minor divergences between trial participants and the NKBC population, but taking these into consideration, upcoming trial outcomes should be generalizable to breast cancer patients with micrometastases in their sentinel lymph node biopsy.

Breast-conserving surgery followed by whole-breast irradiation offers survival benefits over mastectomy without irradiation.

BACKGROUND: The prognostic equivalence between mastectomy and breast-conserving surgery (BCS) followed by radiotherapy was shown in pivotal trials conducted decades ago. Since then, detection and treatment of breast cancer have improved substantially and recent retrospective analyses point towards a survival benefit for less extensive breast surgery. Evidence for the association of such survival data with locoregional recurrence rates is largely lacking. METHODS: The Swedish Multicentre Cohort Study prospectively included clinically node-negative patients with breast cancer who had planned sentinel node biopsy between 2000 and 2004. Axillary lymph node dissection was undertaken only in patients with sentinel node metastases. For the present investigation, adjusted survival analyses were used to compare patients who underwent BCS and postoperative radiotherapy with those who received mastectomy without radiotherapy. RESULTS: Of 3518 patients in the Swedish Multicentre Cohort Study, 2767 were included in the present analysis; 2338 had BCS with postoperative radiotherapy and 429 had mastectomy without radiotherapy. Median follow-up was 156 months. BCS followed by whole-breast irradiation was superior to mastectomy without irradiation in terms of both overall survival (79·5 versus 64·3 per cent respectively at 13 years; P < 0·001) and breast cancer-specific survival (90·5 versus 84·0 per cent at 13 years; P < 0·001). The local recurrence rate did not differ between the two groups. The axillary recurrence-free survival rate at 13 years was significantly lower after mastectomy without irradiation (98·3 versus 96·2 per cent; P < 0·001). CONCLUSION: The present data support the superiority of BCS with postoperative radiotherapy over mastectomy without radiotherapy. The axillary recurrence rate differed significantly, and could be one contributing factor in a complex explanatory model.

Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes.

PURPOSE: The clinical significance of lymph node micrometastases and isolated tumor cells (ITCs) in breast cancer is still controversial. After a median follow-up of 52 months, a report from the Swedish Multicenter Cohort Study presented a worse cancer-specific and event-free survival for patients with micrometastases than node-negative individuals, but could not demonstrate a significant difference in overall survival (OS). Due to the tendency of breast cancer to relapse after more than 5-10 years, we now report the long-term survival of the cohort. METHODS: Between September 2000 and January 2004, 3355 breast cancer patients were included in a prospective cohort. Sentinel lymph node biopsy was always performed. Patients were classified in four groups according to their overall nodal stage: node negative (N0, 2372), ITCs (113), micrometastases (123), and macrometastases (747). Kaplan-Meier survival estimates and Cox proportional hazard regression models were applied. RESULTS: Median follow-up was 156 months. Ten-year cancer-specific survival and OS were significantly lower in case of micrometastases than in N0 (84.7 vs. 93.5%, p = 0.001, and 75.5 vs. 84.2%, p = 0.046, respectively). In case of macrometastases, corresponding survival rates were 82.8 and 74.3%. Only for those aged less than 50 years, cancer-specific survival and OS were significantly worse in case of ITCs than N0. Patients with micrometastases received less often chemotherapy than those with macrometastases (24.4 vs. 53.9%). CONCLUSIONS: Lymph node micrometastases in breast cancer have a prognostic significance. This study demonstrates a similar survival for patients with micrometastases and those with macrometastases, possibly due to systemic undertreatment.

Simplifying Logistics and Avoiding the Unnecessary in Patients With Breast Cancer Undergoing Sentinel Node Biopsy. A Prospective Feasibility Trial of the Preoperative Injection of Super Paramagnetic Iron Oxide Nanoparticles.

PURPOSE: Sentinel node is routinely localized with the intraoperative use of a radioactive tracer, involving challenging logistics. Super paramagnetic iron oxide nanoparticle is a non-radioactive tracer with comparable performance that could allow for preoperative localization, would simplify the procedure, and possibly be of value in axillary mapping before neoadjuvant treatment. The current trial aimed to determine the a priori hypothesis that the injection of super paramagnetic iron oxide nanoparticles in the preoperative period for the localization of the sentinel node is feasible. METHODS: This is a prospective feasibility trial, conducted from 9 September 2014 to 22 October 2014 at Uppsala University Hospital. In all, 12 consecutive patients with primary breast cancer planned for resection of the primary and sentinel node biopsy were recruited. Super paramagnetic iron oxide nanoparticles were injected in the preoperative visit in the outpatient clinic. The radioactive tracer (99mTc) and the blue dye were injected perioperatively in standard fashion. A volunteer was injected with super paramagnetic iron oxide nanoparticles to follow the decline in the magnetic signal in the sentinel node over time. The primary outcome was successful sentinel node detection. RESULTS: Super paramagnetic iron oxide nanoparticles' detection after preoperative injection (3-15 days) was successful in all cases (100%). In the volunteer, axillary signal was presented for 4 weeks. No adverse effects were noted. Conclusion and relevance: Preoperative super paramagnetic iron oxide nanoparticles' injection is feasible and leads to successful detection of the sentinel node. That may lead to simplified logistics as well as the identification, sampling, and marking of the sentinel node in patients planned for neoadjuvant treatment.

Superparamagnetic iron oxide nanoparticles as the sole method for sentinel node biopsy detection in patients with breast cancer.

BACKGROUND: Sentinel node biopsy (SNB) using superparamagnetic iron oxide (SPIO) nanoparticles is a novel method in breast cancer. Several studies have verified the non-inferiority of SPIO compared with the standard use of radioisotope 99m Tc with or without blue dye. The aim of the MONOS study presented here was to evaluate the use of SPIO as a sole tracer and the efficacy of tracer injection in the preoperative setting. METHODS: This prospective cohort study was carried out in two hospitals, one using 99m Tc and the other SPIO. 99m Tc was injected in the morning of the day of surgery or the day before. SPIO was either injected before surgery in the outpatient clinic or 1 h before the operation. RESULTS: A total of 338 consecutive patients with breast cancer underwent 343 procedures; SPIO nanoparticles were used in 184 procedures and 99m Tc-labelled tracer in 159. Detection rates for SPIO and 99m Tc were 95·6 and 96·9 per cent respectively (P = 0·537). All nodes with SPIO uptake were coloured brown. Fewer nodes were retrieved with SPIO (mean 1·35 versus 1·89), regardless of whether blue dye was used (P < 0·001). Preoperative SPIO injection (58·7 per cent of procedures), a median of 16 (range 2-27) days before the procedure, was associated with a better tracer-specific detection rate (95·3 versus 86 per cent; P = 0·031) and retrieval of more nodes (mean 1·43 versus 1·03; P < 0·001) than perioperative administration. Skin staining was present in 39·9 per cent of patients, and was related to breast-conserving surgery and periareolar injection. CONCLUSION: The use of SPIO alone is a safe alternative, with results comparable to those of the standard dual technique using 99m Tc and blue dye. The efficacy of injection in the preoperative setting simplifies logistics and improves performance. Skin staining can be prevented by a deeper peritumoral injection.

Ten-year report on axillary recurrence after negative sentinel node biopsy for breast cancer from the Swedish Multicentre Cohort Study.

BACKGROUND: The omission of axillary lymph node dissection (ALND) in patients with breast cancer with a negative finding on sentinel node biopsy (SNB) has reduced arm morbidity substantially. Early follow-up reports have shown the rate of axillary recurrence to be significantly lower than expected, with a median false-negative rate of 7 per cent for SNB. Long-term follow-up is needed as recurrences may develop late. METHODS: The Swedish Multicentre Cohort Study included 3518 women with breast cancer and a clinically negative axilla, in whom SNB was planned. ALND was performed only in patients with sentinel node metastasis. Twenty-six centres contributed to enrolment between September 2000 and January 2004. The primary endpoint was the axillary recurrence rate and the secondary endpoint was breast cancer-specific survival, calculated using Kaplan-Meier survival estimates. RESULTS: Some 2216 sentinel node-negative patients with 2237 breast cancers were analysed. The median follow-up time was 126 (range 0-174) months. Isolated axillary recurrence was found in 35 patients (1·6 per cent). High histological grade and multifocal tumours were risk factors for axillary recurrence, whereas the removal of more than two sentinel nodes decreased the risk. Fourteen (40 per cent) of 35 patients died as a consequence of axillary recurrence. CONCLUSION: The risk of axillary recurrence remains lower than expected after a negative finding on SNB at 10-year follow-up. Axillary recurrences may occur long after primary surgery, and lead to a significant risk of breast cancer death.

Arm lymphoedema after axillary surgery in women with invasive breast cancer.

BACKGROUND: The primary aim was to compare arm lymphoedema after sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) in women with node-negative and node-positive breast cancer. The secondary aim was to examine the potential association between self-reported and objectively measured arm lymphoedema. METHODS: Women who had surgery during 1999-2004 for invasive breast cancer in four centres in Sweden were included. The study groups were defined by the axillary procedure performed and the presence of axillary metastases: SLNB alone, ALND without axillary metastases, and ALND with axillary metastases. Before surgery, and 1, 2 and 3 years after operation, arm volume was measured and a questionnaire regarding symptoms of arm lymphoedema was completed. A mixed model was used to determine the adjusted mean difference in arm volume between the study groups, and generalized estimating equations were employed to determine differences in self-reported arm lymphoedema. RESULTS: One hundred and forty women had SLNB alone, 125 had node-negative ALND and 155 node-positive ALND. Women who underwent SLNB had no increase in postoperative arm volume over time, whereas both ALND groups showed a significant increase. The risk of self-reported arm lymphoedema 1, 2 and 3 years after surgery was significantly lower in the SLNB group compared with that in both ALND groups. Three years after surgery there was a significant association between increased arm volume and self-reported symptoms of arm lymphoedema. CONCLUSION: SLNB is associated with a minimal risk of increased arm volume and few symptoms of arm lymphoedema, significantly less than after ALND, regardless of lymph node status.

Vitamin C intake and breast cancer mortality in a cohort of Swedish women.

BACKGROUND: Vitamin C may influence cancer progression through its antioxidant properties. However, the evidence from observational epidemiologic studies on vitamin C intake and survival following breast cancer diagnosis is not consistent, and the safety of vitamin C supplements following breast cancer diagnosis has not been extensively studied. METHODS: Using a food-frequency questionnaire we investigated whether vitamin C intake was associated with survival among 3405 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort. RESULTS: From 1987-2010, there were 1055 total deaths with 416 deaths from breast cancer. Women in the highest quartile of pre-diagnosis vitamin C intake had an adjusted HR (95% CI) of breast cancer death of 0.75 (0.57-0.99) compared with those in the lowest quartile (Ptrend=0.03). There was a borderline significant association between vitamin C intake and total mortality (HR=0.84; 95% CI=0.71-1.00; Ptrend=0.08). Among 717 breast cancer cases for whom post-diagnosis supplement use was available, there was no association between vitamin C supplement use (≈1000 mg) and breast cancer-specific mortality (HR=1.06; 95% CI=0.52-2.17). CONCLUSION: Our findings suggest that dietary vitamin C intake before breast cancer diagnosis may be associated with breast cancer survival. In addition, post-diagnosis vitamin C supplementation at the level observed in our population was not associated with survival.

Causes of false-negative sentinel node biopsy in patients with breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection as the routine staging procedure in clinically node-negative breast cancer. False-negative SLN biopsy results in misclassification and may cause undertreatment of the disease. The aim of this study was to investigate whether serial sectioning of SLNs reveals metastases more frequently in patients with false-negative SLNs than in patients with true-negative SLNs. METHODS: This was a case-control study. Tissue blocks from patients with false-negative SLNs, defined as tumour-positive lymph nodes excised at completion axillary dissection or a subsequent axillary tumour recurrence, were reassessed by serial sectioning and immunohistochemical staining. For each false-negative node, two true-negative SLN biopsies were analysed. Tumour and node characteristics in patients with false-negative SLNs were compared with those in patients with a positive SLN by univariable and multivariable regression analysis. RESULTS: Undiagnosed SLN metastases were discovered in nine (18 per cent) of 50 patients in the false-negative group and in 12 (11.2 per cent) of 107 patients in the true-negative group (P = 0.245). The metastases were represented by isolated tumour cells in 14 of these 21 patients. The risk of a false-negative SLN was higher in patients with hormone receptor-negative (odds ratio (OR) 2.50, 95 per cent confidence interval 1.17 to 5.33) or multifocal tumours (OR 3.39, 1.71 to 6.71), or if only one SLN was identified (OR 3.57, 1.98 to 6.45). CONCLUSION: SLN serial sectioning contributes to a higher rate of detection of SLN metastasis. The rate of upstaging of the tumour is similar in false- and true-negative groups of patients.

Coffee and black tea consumption and breast cancer mortality in a cohort of Swedish women.

BACKGROUND: Coffee and black tea contain a mixture of compounds that have the potential to influence breast cancer risk and survival. However, epidemiologic data on the relation between coffee and black tea consumption and breast cancer survival are sparse. METHODS: We investigated the association between coffee and black tea consumption and survival among 3243 women with invasive breast cancer in the Swedish Mammography Cohort. Intake was estimated using a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: From 1987 to 2010 there were 394 breast cancer-specific deaths and 973 total deaths. Coffee and black tea were not associated with breast cancer-specific or overall mortality. Women consuming 4+ cups of coffee per day had a covariate and clinical characteristics-adjusted HR (95% CI) of death from breast cancer of 1.14 (0.71-1.83; p(trend)=0.81) compared with those consuming <1 cup per day. Women consuming 2+ cups of black tea per day had a covariate and clinical characteristics-adjusted HR (95% CI) of death from breast cancer of 1.02 (0.67-1.55; p(trend)=0.94) compared with non-tea drinkers. Caffeine was also not associated with breast cancer-specific (HR for top to bottom quartile=1.06; 95% CI=0.79-1.44; p(trend)=0.71) or overall mortality. CONCLUSION: Our findings suggest that coffee, black tea, and caffeine consumption before breast cancer diagnosis do not influence breast cancer-specific and overall survival.

Prediction of non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastases: evaluation of the tenon score.

INTRODUCTION: Current guidelines recommend completion axillary lymph node dissection (cALND) in case of a sentinel lymph node (SLN) metastasis larger than 0.2 mm. However, in 50%-65% of these patients, the non-SLNs contain no further metastases and cALND provides no benefit. Several nomograms and scoring systems have been suggested to predict the risk of metastases in non-SLNs. We have evaluated the Tenon score. PATIENTS AND METHODS: In a retrospective review of the Swedish Sentinel Node Multicentre Cohort Study, risk factors for additional metastases were analysed in 869 SLN-positive patients who underwent cALND, using uni- and multivariate logistic regression models. A receiver operating characteristic (ROC) curve was drawn on the basis of the sensitivity and specificity of the Tenon score, and the area under the curve (AUC) was calculated. RESULTS: Non-SLN metastases were identified in 270/869 (31.1%) patients. Tumour size and grade, SLN status and ratio between number of positive SLNs and total number of SLNs were significantly associated with non-SLN status in multivariate analyses. The area under the curve for the Tenon score was 0.65 (95% CI 0.61-0.69). In 102 patients with a primary tumour <2 cm, Elston grade 1-2 and SLN metastases ≤2 mm, the risk of non SLN metastasis was less than 10%. CONCLUSION: The Tenon score performed inadequately in our material and we could, based on tumour and SLN characteristics, only define a very small group of patients in which negative non-sentinel nodes could be predicted.

Alcohol intake and mortality among women with invasive breast cancer.

BACKGROUND: Alcohol intake has consistently been associated with increased breast cancer incidence in epidemiological studies. However, the relation between alcohol and survival after breast cancer diagnosis is less clear. METHODS: We investigated whether alcohol intake was associated with survival among 3146 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort. Alcohol consumption was estimated using a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: From 1987 to 2008 there were 385 breast cancer-specific deaths and 860 total deaths. No significant association was observed between alcohol intake and breast cancer-specific survival. Women who consumed 10 g per day (corresponding to approximately 0.75 to 1 drinks) or more of alcohol had an adjusted HR (95% CI) of breast cancer-specific death of 1.36 (0.82-2.26;p(trend)=0.47) compared with non-drinkers. A significant inverse association was observed between alcohol and non-breast cancer deaths. Those who consumed 3.4-9.9 g per day of alcohol had a 33% lower risk of death compared with non-drinkers (95% CI 0.50-0.90;p(trend)=0.04). CONCLUSION: Our findings suggest that alcohol intake up to approximately one small drink per day does not negatively impact breast cancer-specific survival and a half drink per day is associated with a decreased risk of mortality from other causes.

Axillary recurrence rate 5 years after negative sentinel node biopsy for breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection (ALND) as the standard axillary staging procedure in breast cancer. Follow-up studies in SLN-negative women treated without ALND report low rates of axillary recurrence, but most studies have short follow-up, and few are multicentre studies. METHODS: Between September 2000 and January 2004, patients who were SLN-negative and did not have ALND were included in a prospective cohort. Kaplan-Meier estimates were used to analyse the rates of axillary recurrence and survival. The risk of axillary recurrence was also compared in centres with high and low experience with the SLN biopsy (SLNB) technique. RESULTS: A total of 2195 patients with 2216 breast tumours were followed for a median of 65 months. Isolated axillary recurrence was diagnosed in 1·0 per cent of patients. The event-free 5-year survival rate was 88·8 per cent and the overall 5-year survival rate 93·1 per cent. There was no difference in recurrence rates between centres contributing fewer than 150 SLNB procedures to the cohort and centres contributing 150 or more procedures. CONCLUSION: This study confirmed the low risk of axillary recurrence 5 years after SLNB for breast cancer without ALND.

Nurse or surgeon follow-up after rectal cancer: a randomized trial.

AIM: Follow-up programmes consume a large amount of resources with less time for the surgeon to take on new patients. The aim of this randomized study was to compare patient satisfaction, resource utilization and medical safety in patients curatively operated for rectal cancer who were followed up by either a surgeon or a nurse. METHOD: The nurse was trained by the colorectal surgeon before the start of the study. Curatively operated patients were asked to give their consent to participate. Randomization was performed by the stoma therapist. After each consultation, the patient completed a questionnaire. RESULTS: A total of 110 patients (58 men) age 68 (range 41-87) years were included between 2002 and 2005. Only three patients refused participation. Patient satisfaction was high according to the Visual Analogue Scale (VAS): 9.4 for the surgeon and 9.5 for the nurse (NS). Consultation time was longer for the nurse: 24 vs 15 min (P = 0.001), with more blood samples being taken (29%vs 7%, P = 0.002). Radiological investigations exceeding the routine were made in 11%vs 4% (NS) cases. Surgical assistance was needed in 13 of 182 consultations with the nurse [mean 6 (1-15) min, total 75 min]. Distant metastases were detected in seven patients in the surgeon group and eight in the nurse group (P = 0.953). Total costs of follow-up did not differ. CONCLUSION: Patient satisfaction was equally high for the specialist nurse as for the colorectal surgeon. On only a few occasions was surgical assistance necessary and total costs for the follow-up showed no difference. Medical safety appeared uncompromised. Nurse-led follow-up is encouraged.

Chronic pain 5 years after randomized comparison of laparoscopic and Lichtenstein inguinal hernia repair.

BACKGROUND: Chronic postoperative pain is a major drawback of inguinal hernia repair. This study compared the frequency of chronic pain after laparoscopic (totally extraperitoneal patch, TEP) and open (Lichtenstein) repairs. METHODS: A randomized multicentre study with 5 years' follow-up was conducted on men with a primary inguinal hernia. Chronic pain was categorized as mild, moderate or severe by blinded observers. A subgroup analysis was performed on 121 patients who experienced moderate or severe pain at any time during follow-up. RESULTS: Overall, 1370 of 1512 randomized patients underwent surgery, 665 in the TEP and 705 in the Lichtenstein group. The total incidence of chronic pain was 11.0 versus 21.7 per cent at 1 year, 11.0 versus 24.8 per cent at 2 years, 9.9 versus 20.2 per cent at 3 years and 9.4 versus 18.8 per cent at 5 years in the TEP and Lichtenstein groups respectively (P < 0.001). After 5 years, 1.9 per cent of patients in the TEP and 3.5 per cent in the Lichtenstein group reported moderate or severe pain (P = 0.092). Of the 121 patients, 72 (59.5 per cent) no longer reported pain a median of 9.4 (range 6.7-10.8) years after operation. CONCLUSION: Five years after surgery only a small proportion of patients still report moderate to severe chronic pain. Laparoscopic inguinal hernia repair leads to less chronic pain than open repair. REGISTRATION NUMBER: NCT00568269 (http://www.clinicaltrials.gov).

Long-term cost-minimization analysis comparing laparoscopic with open (Lichtenstein) inguinal hernia repair.

BACKGROUND: Laparoscopic surgery has emerged as a new treatment modality for inguinal hernia repair. The aim of the present study was to analyse its long-term costs in relation to those of open repair. METHODS: A randomized multicentre study comparing totally extraperitoneal laparoscopic repair (TEP) with open repair by the Lichtenstein procedure was performed on men with a primary inguinal hernia. Long-term data on recurrences and complications up to 5 years after operation were collected. Taking treatment costs into consideration, a cost-minimization analysis was conducted. RESULTS: A total of 1370 patients had an inguinal hernia repair, 665 in the TEP and 705 in the Lichtenstein group. The total hospital cost for the index operation was 710.6 euro higher for TEP repair (P < 0.001). Including costs associated with recurrences and complications, this difference increased to 795.1 euro (P < 0.001). Taking community costs into account, the difference decreased by 503.1 euro to 292.0 euro (P = 0.024). CONCLUSION: This cost-minimization analysis, including complications, reoperations and community costs during follow-up of 5 years, showed that laparoscopic inguinal hernia repair had a small but significant increase in overall costs compared with open repair.

Dietary lignans and postmenopausal breast cancer risk by oestrogen receptor status: a prospective cohort study of Swedish women.

Among the 51,823 postmenopausal women in the Swedish Mammography Cohort, we investigated breast cancer risk in relation to the FFQ-based estimated lignan intake by oestrogen receptor (ER) and progesterone receptor (PR) subtypes. A significant 17% risk reduction for breast cancer overall in the high lignan quartile was observed, especially among PMH user (P interaction<0.010), but no heterogeneity across ER/PR subtypes.

NK-cell and T-cell functions in patients with breast cancer: effects of surgery and adjuvant chemo- and radiotherapy.

Breast cancer is globally the most common malignancy in women. Her2-targeted monoclonal antibodies are established treatment modalities, and vaccines are in late-stage clinical testing in patients with breast cancer and known to promote tumour-killing through mechanisms like antibody-dependent cellular cytotoxicity. It is therefore increasingly important to study immunological consequences of conventional treatment strategies. In this study, functional tests and four-colour flow cytometry were used to detect natural killer (NK)-cell functions and receptors as well as T-cell signal transduction molecules and intracellular cytokines in preoperative breast cancer patients, and patients who had received adjuvant radiotherapy or adjuvant combined chemo-radiotherapy as well as in age-matched healthy controls. The absolute number of NK cells, the density of NK receptors as well as in vitro quantitation of functional NK cytotoxicity were significantly higher in preoperative patients than the post-treatments group and controls. A similar pattern was seen with regard to T-cell signalling molecules, and preoperative patients produced significantly higher amounts of cytokines in NK and T cells compared to other groups. The results indicate that functions of NK and T cells are well preserved before surgery but decrease following adjuvant therapy, which may speak in favour of early rather than late use of immunotherapeutic agents such as trastuzumab that may depend on intact immune effector functions.