Impact of rapid genetic counselling and testing on the decision to undergo immediate or delayed prophylactic mastectomy in newly diagnosed breast cancer patients: findings from a randomised controlled trial.

BACKGROUND: Female breast cancer patients with a BRCA1/2 mutation have an increased risk of contralateral breast cancer. We investigated the effect of rapid genetic counselling and testing (RGCT) on choice of surgery. METHODS: Newly diagnosed breast cancer patients with at least a 10% risk of a BRCA1/2 mutation were randomised to an intervention group (offer of RGCT) or a control group (usual care; ratio 2 : 1). Primary study outcomes were uptake of direct bilateral mastectomy (BLM) and delayed contralateral prophylactic mastectomy (CPM). RESULTS: Between 2008 and 2010, we recruited 265 women. On the basis of intention-to-treat analyses, no significant group differences were observed in percentage of patients opting for a direct BLM (14.6% for the RGCT group vs 9.2% for the control group; odds ratio (OR) 2.31; confidence interval (CI) 0.92-5.81; P=0.08) or for a delayed CPM (4.5% for the RGCT group vs 5.7% for the control group; OR 0.89; CI 0.27-2.90; P=0.84). Per-protocol analysis indicated that patients who received DNA test results before surgery (59 out of 178 women in the RGCT group) opted for direct BLM significantly more often than patients who received usual care (22% vs 9.2%; OR 3.09, CI 1.15-8.31, P=0.03). INTERPRETATION: Although the large majority of patients in the intervention group underwent rapid genetic counselling, only a minority received DNA test results before surgery. This may explain why offering RGCT yielded only marginally significant differences in uptake of BLM. As patients who received DNA test results before surgery were more likely to undergo BLM, we hypothesise that when DNA test results are made routinely available pre-surgery, they will have a more significant role in surgical treatment decisions.

Should we abandon wire-guided localization for nonpalpable breast cancer? A plea for wire-guided localization.

BACKGROUND AND AIMS: To evaluate wire-guided localization for nonpalpable breast cancer regarding procedure and surgery-related outcome in a nonteaching community hospital in the Netherlands. MATERIAL AND METHODS: A consecutive series of 117 patients who were treated with breast-conserving surgery after wire-guided localization for nonpalpable breast cancer between January 2006 and December 2010 was retrospectively analyzed. The patients' digital records were reviewed for patient, radiological, histological, and surgical characteristics. In order to quantify the excess resected tissue, a calculated resection ratio was determined by dividing the total resection volume by the optimal resection volume. The optimal resection volume was defined as a spherical tumor volume with an added 1.0 cm margin. The total resection volume was defined as the corresponding ellipsoid. RESULTS: There were no procedure-related complications. There were two postoperative hemorrhages. Margins were clear in 92.3% of the cases after the first surgical procedure. Eight (6.8%) patients required two operations and one (0.9%) patient required three operations in order to obtain negative margins. Breast conservation was possible in 113 (96.6%) patients. The median calculated resection ratio was 1.87 (range 0.47-14.92). CONCLUSIONS: This study proves that it is possible to obtain excellent results performing breast-conserving surgery for nonpalpable breast cancer regarding margin status, total amount of operations, and the ratio between tumor and resected tissue volume using wire-guided localization as a localization tool.

The effect of the introduction of the ERAS protocol in laparoscopic total mesorectal excision for rectal cancer.

OBJECTIVE: The aim of the study was to determine whether the introduction of the Enhanced Recovery after Surgery (ERAS) protocol in laparoscopic total mesorectal excision (TME) for rectal cancer offers additional advantages concerning postoperative hospital stay compared to laparoscopy and conventional care. METHODS: A consecutive series of patients that underwent a laparoscopic TME for rectal cancer in a single institution between January 2004 and July 2009 were retrospectively included in this study. The ERAS protocol was introduced in this cohort in January 2007. The study cohort was divided in a conventional care group and an ERAS group. Both groups were compared for primary and secondary outcome measures. The primary outcome measure was postoperative length of hospital stay. RESULTS: Seventy-six patients were included: 43 in the ERAS group and 33 in the conventional care (control) group. Median hospital stay was 7 days (range 2-83 days) in the ERAS group and 10 days (range 4-74 days) in the control group (p = 0.04). Return of bowel function occurred on days 2 and 3 respectively (p < 0.001). There were no significant differences between both groups concerning postoperative complications, readmission rate and reoperations. Thirty-day mortality was absent in both groups. CONCLUSION: These results suggest that the introduction of the ERAS protocol in laparoscopic TME leads to a further reduction in length of hospital stay.

The ERAS protocol reduces the length of stay after laparoscopic colectomies.

BACKGROUND: The Enhanced Recovery After Surgery (ERAS) protocol, which is developed to enhance postoperative recovery of patients treated with open colorectal surgery, has been widely adopted. The ERAS protocol has also been introduced in patients treated with laparoscopic colectomy, without data to support its additional value. We investigated whether laparoscopic colectomy in combination with the use of the ERAS protocol leads to a reduction of postoperative length of stay compared to laparoscopic colectomy with conventional care. METHODS: We performed a comprehensive medical record review. Inclusion criteria were patients who had undergone a laparoscopic colectomy at a single center between April 2004 and September 2009 (n = 186). The ERAS protocol had been introduced at the end of 2006. We divided the patients in a pre-ERAS group (n = 77), and an ERAS group (n = 109). We compared the baseline characteristics of both groups. The primary outcome was postoperative length of stay. RESULTS: We did not find significant differences in gender, age, body mass index (BMI), diabetes mellitus (DM), American Society of Anesthesiologists (ASA) classification, and diagnosis and type of surgery between the two groups. Median postoperative length of stay was 6 days (range = 2-28) in the pre-ERAS group and 4 days (range = 2-55) in the ERAS group (P = 0.007). Median return of bowel function was 3 days (range = 1-6) in the pre-ERAS group and 2 days (range = 1-5) in the ERAS group (P < 0.001). We did not find significant differences in postoperative procedure-related complications (wound infection, anastomotic leakage, abscesses), postoperative morbidity, 30-day readmission, 30-day reoperation, and 30-day mortality. CONCLUSIONS: The postoperative length of stay was significantly reduced in the ERAS group without differences in patient outcome. It is suggested that these results are the effect of a combination of the ERAS protocol with laparoscopic colectomy.

The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome of invasive ductal breast carcinoma.

AIMS: To clarify MUC1 patterns in invasive ductal breast carcinoma and to relate them to clinicopathological parameters, coexpression of other biological markers and prognosis. METHODS AND RESULTS: Samples from 243 consecutive patients with primary ductal carcinoma were incorporated into tissue microarrays (TMAs). Slides were stained for MUC1, oestrogen receptor (ER), progesterone receptor (PR), Her2/neu, p53 and cyclin D1. Apical membrane MUC1 expression was associated with smaller tumours (P = 0.001), lower tumour grades (P < 0.001), PR positivity (P = 0.003) and increased overall survival (OS; P = 0.030). Diffuse cytoplasmic MUC1 expression was associated with cyclin D1 positivity (P = 0.009) and increased relapse-free survival (RFS; P = 0.034). Negativity for MUC1 was associated with ER negativity (P = 0.004), PR negativity (P = 0.001) and cyclin D1 negativity (P = 0.009). In stepwise multivariate analysis MUC1 negativity was an independent predictor of both RFS [hazard ratio (HR) 3.5, 95% confidence interval (CI) 1.5, 8.5; P = 0.005] and OS (HR 14.7, 95% CI 4.9, 44.1; P < 0.001). CONCLUSIONS: The expression pattern of MUC1 in invasive ductal breast carcinoma is related to tumour characteristics and clinical outcome. In addition, negative MUC1 expression is an independent risk factor for poor RFS and OS, besides 'classical' prognostic indicators.

The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome in 'pure' ductal carcinoma in situ of the breast.

AIMS: To classify MUC1 according to five predefined expression patterns in ductal carcinoma in situ (DCIS) and related clinicopathological parameters, coexpression of other biological markers and prognosis. METHODS AND RESULTS: With a manual tissue arrayer, 92% (n = 80) of the 87 DCIS samples were successfully targeted. Immunohistochemistry was carried out for MUC1, oestrogen receptor (ER), progesterone receptor (PR), Her2/Neu, p53 and cyclin D1. Entire membrane expression was related to Her2/neu negativity (P =0.042). Apical membrane expression was associated with low grade (P = 0.027), Her2/neu negativity (P = 0.014) and PR positivity (P = 0.005). Focal cytoplasmic expression was related to high grade (P = 0.006). Diffuse cytoplasmic expression was associated with high grade (P = 0.004), large tumour size (P = 0.046), Her2/neu positivity (P =0.042) and cyclin D1 positivity (P = 0.002). On the basis of these analyses the four patterns were reclassified as membranous or cytoplasmic expression. On multivariate analysis, cytoplasmic MUC1 expression (hazard ratio 8.5, 95% confidence interval 1.0, 73.0; P = 0.04) was the only independent predictor of local recurrence. CONCLUSIONS: Four patterns of MUC1 expression are recognized in DCIS that suggest a relationship to functional differentiation and can be simplified into two types that are clinically relevant and could therefore be helpful in the distinction between different subgroups of DCIS.

Compliance with guidelines is related to better local recurrence-free survival in ductal carcinoma in situ.

The aim was to study the effect of compliance with guidelines on local recurrence (LR)-free survival in patients treated for ductal carcinoma in situ (DCIS). From January 1992 to December 2003, 251 consecutive patients had been treated for DCIS in two hospitals in the North Netherlands. Every case in this two-hospital sample was reviewed in retrospect for its clinical and pathological parameters. It was determined whether treatment had been carried out according to clinical guidelines, and outcomes in follow-up were assessed. In addition, all patients treated for DCIS in this region (n=1389) were studied regarding clinical parameters, in order to determine whether the two-hospital sample was representative of the entire region. In the two-hospital sample, 31.4% (n=79) of the patients had not been treated according to the guidelines. Positive margins were associated with LR (hazard ratio (HR)=4.790, 95% confidence interval (CI) 1.696-13.531). Breast-conserving surgery and deviation from the guidelines were independent predictors of LR (HR=7.842, 95% CI 2.126-28.926; HR=2.778, 95% CI 0.982-6.781, respectively). Although the guidelines changed over time, time was not a significant factor in predicting LRs (HR=1.254, 95% CI 0.272-5.776 for time period 1992-1995 and HR=1.976, 95% CI 0.526-7.421 for time period 1996-1999). Clinical guidelines for the treatment of patients with DCIS have been developed and updated from existing literature and best evidence. Compliance with the guidelines was an independent predictor of disease-free survival. These findings support the application of guidelines in the treatment of DCIS.

Ductal carcinoma in situ presenting as microcalcifications: the effect of stereotactic large-core needle biopsy on surgical therapy.

The aim of this investigation was to study the efficacy of surgical therapy in patients with non-palpable ductal carcinoma in situ (DCIS) presenting as microcalcifications diagnosed by means of stereotactic large-core needle biopsy (SCNB). This is a retrospective study with a historical control group within a 12-year period. Two groups of consecutive patients diagnosed with DCIS (1991-2002) by means of needle-localised open breast biopsy (NLBB, n=49) and SCNB (n=51) were studied. Both groups were comparable for clinical, radiological and pathological characteristics. The therapeutic interval (time from presentation to definitive of therapy) was 62-days in the SCNB group versus 32-days in the NLBB group (p<0.001). In the SCNB group fewer surgical procedures were required for completion of surgical therapy (p=0.006) and after local excision the surgical margins were more often tumour free (p=0.002). It is postulated that the need for fewer surgical procedures and the greater frequency of tumour-free margins after local excision may be attributable to SCNB.

[The stumbling toddler]. / De zwalkende kleuter.

Four previously healthy children, two boys aged 5 and one boy and one girl aged 4 more or less acutely developed a stumbling gait. The causes varied from benign such as postviral acute cerebellar ataxia and benign paroxysmal vertigo to potentially life-threatening such as intoxication with benzodiazepines and medulloblastoma. Treatment led to complete or partial recovery. (Sub)acute balance disorders in previously healthy children can be due to cerebellar ataxia, vestibular disorders and abnormal proprioception. Ancillary investigations are warranted in case of gradually developing ataxia, accompanying neurological deficits, suspicion of intoxication, recurrent or familial ataxia, no spontaneous remission or even progression. In children with an isolated cerebellar ataxia without these features, ancillary investigations may be avoided, although in such cases careful follow-up remains necessary.