Migrant breast cancer patients and their participation in genetic counseling: results from a registry-based study.

Certain ethnic groups seem to have less access to cancer genetic counseling. Our study was to investigate the participation in cancer genetic counseling among migrant breast cancer patients of Turkish and Moroccan origin. Hospital medical records of Turkish and Moroccan and of a comparative group of non-Turkish/Moroccan newly diagnosed breast cancer patients were studied. All women were diagnosed between 2007 and 2012. Eligibility for genetic counseling was assessed with a checklist. A total of 156 Turkish/Moroccan patients were identified, and 321 patients were assigned to the comparative group. About one third (35%) of the Turkish/Moroccan patients fulfilled criteria for breast cancer genetic counseling, compared to 21% of the comparative group (P = 0.001); this was largely due to a relatively young age at diagnosis in the migrant group (26% <40 years vs 5% in the comparative group, P = 0.0001). Uptake of genetic counseling among eligible patients was 47% in the migrant group and 56% in the comparative group; differences in uptake were seen among the patients diagnosed before 40 years of age (48% in the migrant group vs 81% in the comparative group; P = 0.021). When adjusted for age at diagnosis, ethnicity was associated with discussing referral to genetic counseling and its actual uptake. The Turkish/Moroccan ethnicity appears to be associated with a lower uptake of genetic counseling, mainly caused by the lower uptake in the young age-group. The major barrier to participation in genetic counseling seems to lie within the referral process.

Intensified follow-up in colorectal cancer patients using frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging: Results of the randomized "CEAwatch" trial.

AIM: The value of frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging for detecting recurrent disease in colorectal cancer (CRC) patients was investigated in search for an evidence-based follow-up protocol. METHODS: This is a randomized-controlled multicenter prospective study using a stepped-wedge cluster design. From October 2010 to October 2012, surgically treated non-metastasized CRC patients in follow-up were followed in eleven hospitals. Clusters of hospitals sequentially changed their usual follow-up care into an intensified follow-up schedule consisting of CEA measurements every two months, with imaging in case of two CEA rises. The primary outcome measures were the proportion of recurrences that could be treated with curative intent, recurrences with definitive curative treatment outcome, and the time to detection of recurrent disease. RESULTS: 3223 patients were included; 243 recurrences were detected (7.5%). A higher proportion of recurrences was detected in the intervention protocol compared to the control protocol (OR = 1.80; 95%-CI: 1.33-2.50; p = 0.0004). The proportion of recurrences that could be treated with curative intent was higher in the intervention protocol (OR = 2.84; 95%-CI: 1.38-5.86; p = 0.0048) and the proportion of recurrences with definitive curative treatment outcome was also higher (OR = 3.12, 95%-CI: 1.25-6.02, p-value: 0.0145). The time to detection of recurrent disease was significantly shorter in the intensified follow-up protocol (HR = 1.45; 95%-CI: 1.08-1.95; p = 0.013). CONCLUSION: The CEAwatch protocol detects recurrent disease after colorectal cancer earlier, in a phase that a significantly higher proportion of recurrences can be treated with curative intent.

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.

Constraints of vowels and consonants on lexical selection: cross-linguistic comparisons.

Languages differ in the constitution of their phonemic repertoire and in the relative distinctiveness of phonemes within the repertoire. In the present study, we asked whether such differences constrain spoken-word recognition, via two word reconstruction experiments, in which listeners turned non-words into real words by changing single sounds. The experiments were carried out in Dutch (which has a relatively balanced vowel-consonant ratio and many similar vowels) and in Spanish (which has many more consonants than vowels and high distinctiveness among the vowels). Both Dutch and Spanish listeners responded significantly faster and more accurately when required to change vowels as opposed to consonants; when allowed to change any phoneme, they more often altered vowels than consonants. Vowel information thus appears to constrain lexical selection less tightly (allow more potential candidates) than does consonant information, independent of language-specific phoneme repertoire and of relative distinctiveness of vowels.

Loss of imprinting of IGF2 and not H19 in breast cancer, adjacent normal tissue and derived fibroblast cultures.

Insulin-like growth factors are involved in the paracrine growth regulation of human breast tumor cells. IGF2 is imprinted in most tissues, and shows expression of the paternal allele only. To investigate whether disruption of this monoallelic IGF2 expression is involved in breast cancer development, a series of primary tumors and adjacent, histologically normal, breast tissue samples, as well as matched primary in vitro fibroblast cultures were studied. Biallelic expression (partial) of IGF2 was found in the majority of in vivo samples, and corresponding fibroblast cultures, while monoallelic expression was found in a normal breast sample. In contrast, H19, a closely apposed, but reciprocally imprinted gene, assumed to be regulated by a common control element, showed retention of monoallelic H19 expression in all in vivo and in the majority of in vitro samples. These data indicate that IGF2, but not H19, is prone to loss of imprinting in breast cancer.

[Isolated traumatic dorsal dislocation of the metacarpophalangeal joint of the index finger]. / Geïsoleerde traumatische dorsale luxatie in het metacarpofalangeale gewricht van de wijsvinger.

A woman aged 36 sustained a dislocation of the metacarpophalangeal joint of the index finger occurred during a volleyball match. It appeared to be a complex dislocation with entrapment of soft tissue, which is rare. Open reduction with a volar approach gave a good result. The postoperative course was uneventful. Adequate treatment necessitates rapid diagnosis. The herniation of the head of the metacarpal bone through the volar surface precluded closed repositioning. The palmar surgical approach is difficult but gives good anatomical results. The dorsal approach is safer but more laborious. Rapid mobilization is necessary for a good long-term result.

Ultrasound-guided aspiration biopsy for detection of nonpalpable axillary node metastases in breast cancer patients: new diagnostic method.

This study was designed to evaluate the accuracy of ultrasonography alone and in combination with fine-needle aspiration biopsy (FNAB) for detection of axillary metastases of nonpalpable lymph nodes in breast cancer patients. Ultrasonography was carried out in 150 axillas of 148 patients (mean age 57 years, range 30-80 years); and in 93 axillas lymph nodes were detected. Nodes were described according to their dimension and echo patterns and were compared with histopathologic results. FNAB was carried out in 81 axillas (122 nodes). The sensitivity of ultrasonography was highest (87%) when size (length >5 mm) was used as criterion for malignancy, but the specificity was rather low (56%). When nodes with a malignant pattern (echo-poor or inhomogeneous) were visualized, specificity was 95%. Ultrasound-guided FNAB had a sensitivity of 80% and a specificity of 100% and detected metastases in 63% of node-positive patients. It is concluded that FNAB is an easy, reliable, inexpensive method for identifying patients with positive nodes. In the case of negative findings, other diagnostic procedures to exclude lymph node metastases, such as sentinel node mapping, could be performed.

Do weak syllables count for newborns?

Does the newborn's well-known sensitivity to human speech include awareness of the distinction between strong and weak syllables, as has been shown for older infants and adults? The non-nutritive high-amplitude sucking paradigm was used to investigate whether weak syllables play a role in neonate perceptual representation. Two-day-old French infants were tested on their capacity to discriminate phonetically highly varied words containing syllables with various strong vowels versus the weak, reduced vowel schwa in natural, isolated English words. Twenty infants heard lists of weak-strong and lists of strong words (e.g., belief, control, etc. versus nose, dream, etc.) and 20 heard lists of weak-strong and strong-strong words (e.g., belief, control, etc. versus volume, rhubarb, etc.). The results show that weak-strong words were reliably distinguished from strong words, but not from strong-strong words. Taken together, the findings indicate that a weak, reduced vowel is equivalent to a strong, full vowel to the extent that both count as syllabic nuclei. Moreover, this global equivalence in terms of number of syllabic constituents apparently over-rules the more local acoustic difference between strong and weak vowels. The role of syllabic/vocalic information in neonate representation is discussed.

Vowel mutability and lexical selection in English: evidence from a word reconstruction task.

This study introduces a new paradigm for investigating lexical processing. First, an analysis of data from a series of word-spotting experiments is presented suggesting that listeners treat vowels as more mutable than consonants in auditory word recognition in English. In order to assess this hypothesis, a word reconstruction task was devised in which listeners were required to turn word-like nonwords into words by adapting the identity of either one vowel or one consonant. Listeners modified vowel identity more readily than consonant identity. Furthermore, incorrect responses more often involved a vowel change than a consonant change. These findings are compatible with the proposal that English listeners are equipped to deal with vowel variability by assuming that vowel identity is comparatively underdefined. The results are discussed in the light of theoretical accounts of speech processing.

Speeded detection of vowels: a cross-linguistic study.

In four experiments, listeners' response times to detect vowel targets in spoken input were measured. The first three experiments were conducted in English. In two, one using real words and the other, nonwords, detection accuracy was low, targets in initial syllables were detected more slowly than targets in final syllables, and both response time and missed-response rate were inversely correlated with vowel duration. In a third experiment, the speech context for some subjects included all English vowels, while for others, only five relatively distinct vowels occurred. This manipulation had essentially no effect, and the same response pattern was again observed. A fourth experiment, conducted in Spanish, replicated the results in the first three experiments, except that miss rate was here unrelated to vowel duration. We propose that listeners' responses to vowel targets in naturally spoken input are effectively cautious, reflecting realistic appreciation of vowel variability in natural context.

Detection of liver metastases from colorectal carcinoma: is there a place for routine computed tomography arteriography?

BACKGROUND: A prospective evaluation of the liver by preoperative ultrasonography, conventional computed tomography (CT), and continuous CT angiography (CCTA) was performed in 60 patients with primary or secondary colorectal carcinoma. METHODS: The standards of reference were palpation of the liver and intraoperative ultrasonography. The imaging techniques were assessed independently of each other. RESULTS: In 37 patients 105 liver metastases were identified; 23 patients had no metastases. CCTA and a high sensitivity of 94% (99 lesions identified) in contrast to ultrasonography (48%) and conventional CT (52%). The superiority of CCTA was also manifest in lesions less than 1 cm in diameter. However, the high sensitivity was accompanied by a high false-positive rate, particularly because of variations in the perfusion of normal liver parenchyma. Overall, CCTA had the highest accuracy (74%) compared with ultrasonography and CT (both 57%). The data indicate that preoperative ultrasonography and conventional CT have low sensitivity in the detection of liver metastases. CONCLUSIONS: Although CCTA seems to be superior to other preoperative imaging techniques, the too low specificity will hamper its routine application in patients with hepatic metastases from colorectal carcinoma.

Differential regulation of breast tumor cell proliferation by stromal fibroblasts of various breast tissue sources.

A stromal fibroblast-mediated paracrine regulation of epithelial tumor cell proliferation and differentiation plays an important role in the development and progression of breast tumors. We have studied the paracrine growth regulation of various phenotypically different breast cancer cell lines using conditioned serum-free media (C-SFM) from primary breast fibroblasts. Fibroblast cultures were established from malignant primary tumors and adjacent normal breast tissue, benign fibroadenomas, cosmetic reduction mammoplasties and breast skin tissues. All fibroblast-conditioned media were shown to stimulate the proliferation of breast cancer cell lines. However, the C-SFM-induced MCF-7 proliferative response was shown to be significantly higher than the proliferative response observed with any of the other cell lines tested. More importantly, the MCF-7 proliferative response obtained with malignant tumor tissue fibroblast C-SFM was shown to be significantly higher than the response to C-SFM from paired (and unpaired) normal adjacent breast tissue fibroblasts. The MCF-7 proliferative response to fibroblast C-SFM from normal tissue (adjacent to the tumor) was further shown to be comparable to the MCF-7 response using benign or reduction mammoplastic tissue fibroblast C-SFM. In addition, we show that IGFs are only partly responsible for the observed proliferative effect of the C-SFMs, while EGF, TGF alpha and basic-FGF are shown not to be involved. We conclude that stromal fibroblasts can differentially regulate breast cancer cell proliferation. Both the fibroblast's tissue source as well as the target tumor cell's phenotype will determine the extent of the proliferative response.

[Expectant management concerning the breast in 5 patients with occult breast carcinoma]. / Expectatief beleid ten aanzien van de mamma bij 5 patiënten met occult mammacarcinoom.

Five women, between 53 and 78 years old, had axillary lymph node disseminations without a primary breast tumour being found at clinical and radiological investigations. There is much uncertainty about the treatment to be applied in such cases. The patients' breasts were left untreated. One patient had a manifest breast tumour after 6 months' follow-up. The other four patients did not show any sign of a primary tumour after a median follow-up of 26 months (21-96). An expectative policy has already found support in medical literature. The axilla should preferably be treated with axillary lymph node dissection.

Should tamoxifen be a primary treatment choice for elderly breast cancer patients with locoregional disease?

UNLABELLED: To determine the efficacy of tamoxifen as primary treatment for elderly breast cancer patients with locoregional disease, the medical records of 85 patients of 75 years and older were reviewed. The median follow-up was 28 months (range 3-97 mo). Complete remission occurred in twelve (14.1%) patients. All of these patients remained in remission until death or closing date of the study. Twenty (23.5%) patients responded with a partial remission; 5 of them subsequently developed tumor progression. Thirteen (15.3%) patients developed initial tumor progression and 39 (45.9%) had disease stabilisation. Nineteen of this latter group subsequently developed tumor progression. Out of 37 (43.5%) patients with tumor progression, 14 patients were salvaged by surgery (n = 13) or radiotherapy (n = 1). Until the closing date of the study, disease could not be controlled by secondary treatment in 12 patients who subsequently died of breast cancer. Twenty-two of the 37 patients were unfit for surgical treatment at progression, of whom 14 were operable at diagnosis. The actuarial 5-year observed survival rate was 40% for the whole patient group. CONCLUSIONS: Although some patients (14.1%) managed to maintain a long lasting complete remission, caution should be preserved in using tamoxifen as first-line treatment, because of the high risk of treatment failures. As long as factors can not be identified to predict which subgroups of patients will respond to tamoxifen with a remission lasting for their life-time, tamoxifen may only provide an acceptable alternative for elderly breast cancer patients who are too frail or are unwilling to undergo surgery or radiotherapy. For elderly patients in good physical condition, primary treatment by (ABSTRACT TRUNCATED AT 250 WORDS)

Transforming growth factor beta secretion from primary breast cancer fibroblasts.

Transforming growth factor beta (TGF-beta) is a hormonally regulated growth inhibitor with autocrine and/or paracrine functions in human breast cancer. In vivo, enhanced immunohistochemical staining of extracellular TGF-beta 1 has been detected around stromal fibroblasts in response to the antiestrogen treatment. We have investigated the effects of tamoxifen on the production of TGF-beta by primary human breast fibroblast cultures in serum-free medium. Highly variable levels of mainly latent TGF-beta 1 were detected in conditioned media from both tumor and normal tissue derived fibroblasts. Hydroxy-tamoxifen was shown to increase latent TGF-beta 1 secretion in three of the eight tumor tissue-derived fibroblast cultures. Such effect of hydroxy-tamoxifen was not observed in fibroblast cultures established from normal adjacent breast tissue.

Management of extended radionecrosis in the pelvic area with repeated surgical debridement and omental transposition.

Extended radionecrosis in the pelvic area is a disaster occurring in a minority of patients treated with radiotherapy. Extensive excisional procedures, including pelvic exenteration, have been recommended, but carry high morbidity and mortality rates. Alternative treatment strategies are needed to improve survival and increase the quality of life in these patients. We retrospectively analysed the charts of eight patients treated for radionecrosis in the pelvic area between 1985 and 1991. During this period deviatory procedures, repeated but limited debridement and the early incorporation of an omental flap in the ischemic area were used in an attempt to avoid exenteration, but effectively stop further progression of infection and necrosis. The patients underwent a median of five surgical interventions (range: 2 to 21) for 10 sites of radionecrosis. The total of 61 procedures consisted of debridement (29), omental pedicle grafting (6), deviation of urinary tract (3) or intestinal tract (4) and including procedures due to complications (21). They were hospitalized for a median duration of 95 days (range 43-155) divided over several admissions (median 3, range 2-8). One patient died of sepsis during treatment. Complete recovery was achieved in all surviving patients with a median of 12 months (range: 9 to 20 months) after initial surgery. Early surgery, the limited extent of the procedures and omental transposition were the main components of our approach. We conclude that this approach has an acceptable morbidity and mortality rate, while a relatively good quality of life is achieved.

Axillary nodal metastases from an occult primary consistent with breast carcinoma.

The records of 15 women presenting with axillary nodal metastases from an occult primary consistent with breast carcinoma were reviewed. Nine patients underwent complete axillary clearance and in six the clinical mass only was excised. Radiotherapy to the axilla was given to eight patients. One woman underwent mastectomy at the time of axillary surgery but no tumour was found in the excised breast; in the remaining 14 patients the breast was left untreated. One premenopausal woman received adjuvant systemic chemotherapy and one postmenopausal patient was given tamoxifen. Three patients died from recurrent disease at 16, 50 and 56 months after treatment of the axillary mass; one is alive at 42 months with systemic recurrence. In two of these patients the tumour in the breast became apparent before other metastases. Eleven patients survived for a median of 92 (range 18-144) months without evidence of disease. The prognosis of this patient group is better than that generally reported for stage II breast carcinoma.

[Endometriosis of the rectum]. / Endometriosis van het rectum.

Intestinal endometriosis is a diagnostic and therapeutic problem. In case the rectal wall is involved the physical signs of the endometriosis may mimic rectal carcinoma. Suspicion of the correct diagnosis can be aroused by a thorough history that will uncover the periodicity of symptoms e.g. cyclic bleeding. We present two patients with rectal endometriosis externa who were eventually treated successfully by surgery. Treatment may consist of hormonal therapy, although surgery will be necessary sooner or later in the majority of patients.