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.

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.

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.

Angiosarcoma of the breast following lumpectomy, axillary lymph node dissection, and radiotherapy for primary breast cancer: three case reports and a review of the literature.

INTRODUCTION: One of the risks of therapeutic irradiation is the development of secondary malignant tumors. In this paper three cases are reported of angiosarcoma of the breast following breast-conserving surgery and irradiation for primary breast cancer, and the literature is reviewed. METHODS AND MATERIALS: Until now, 13 other cases of postirradiation angiosarcoma of the breast have been reported. The mean interval between treatment of primary breast cancer and the development of angiosarcoma in these 16 patients is 76 months. The clinical aspect is typical with multiple bluish or purple nodules of the skin, purple discolorations, erythematous maculas or areas, sometimes combined with ulceration, edema, or a palpable mass. Mammography does not necessarily raise suspicion and the interpretation of fine-needle aspiration or biopsy may be difficult. RESULTS: In all patients mastectomy was performed, Follow-up data are available for 12 cases. Two patients died of extensive local recurrences and one of distant metastases. CONCLUSION: Angiosarcoma of the previously irradiated breast is an extremely rare tumor and diagnosis may be difficult. The number of patients with long-term follow-up after breast-conserving therapy is growing fast. Therefore, the authors advise to pay special attention to uncommon skin changes of the treated breast, since clinical suspicion is the main clue to the diagnosis of postirradiation angiosarcoma. The primary therapy is (simple) mastectomy if wide tumor-free margins can be achieved. There is no indication for standard adjuvant chemotherapy or irradiation.

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.

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.

Subcutaneous heparin and postoperative wound hematomas. A prospective, double-blind, randomized study.

A prospective, double-blind, controlled study was conducted to assess the incidence of postoperative wound hematomas associated with low-dose subcutaneous heparin therapy among patients undergoing surgery for a single inguinal hernia. The groups were well matched. The results indicate that low-dose heparin therapy is associated with more wound hematomas. Complications of low-dose heparin therapy and new ways to avoid these complications are discussed. The indications for the prophylactic administration of low-dose heparin therapy need careful assessment.

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.

Subcutaneous tumor growth complicating the positioning of Denver shunt and intrapleural port-à-cath in mesothelioma patients.

Patients with malignant ascites and malignant pleural fluid from abdominal or pleural mesothelioma underwent the positioning of Denver type peritoneovenous shunt or intrapleural catheter. They developed tumor growth in the subcutaneous tissue surrounding the devices throughout their courses. Neoplastic seeding is a potential complication of the positioning of shunts and catheters in cavities filled with fluid rich in tumor cells.

Duodenal complications of gynecological malignancies.

Isolated para-aortic lymph node metastasis leading to intestinal complications is uncommon and diagnosis may therefore be delayed. In the present report duodenal bleeding, obstruction and perforation due to isolated para-aortic lymph node metastasis from stage I uterine malignancies are described. Knowledge of these potential problems may lead to early recognition and planning of treatment.

[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.

[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.

[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.

Marfan's syndrome and isolated aneurysm of the abdominal aorta.

A 43 year old woman presented with an aneurysm of the abdominal aorta. Marfan's syndrome was diagnosed as the underlying cause of the aneurysm. An isolated aneurysm as presenting sign of Marfan's syndrome is rare. In a review of published reports about 30 cases were found.

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.

Aortocaval fistula: an easily missed diagnosis.

Four cases of rupture of an abdominal aortic aneurysm into the inferior vena cava are presented. Clinical diagnosis may be difficult because characteristic symptoms are not always present. It is important to recognize the symptoms of an aortocaval fistula as it is usually rapidly fatal. Recognition must lead to immediate surgical intervention. Special attention must be paid to prevent the serious complications inherent in this syndrome such as copious venous bleeding. Preoperatively, strict monitoring of intravenous transfusion is essential. During the operation care in handling the aneurysm is necessary to avoid pulmonary embolism. Surgical closure of the fistula is easy from within the aneurysm.

Carcinoma of the duodenum.

Primary carcinoma of the duodenum is an uncommon tumor of the gastrointestinal tract. We reviewed the histories of ten patients seen between 1976 and 1986. Some of the patients with tumors in the second part of the duodenum presented with clinically evident jaundice. The symptom complex of all other patients was compatible with many benign diseases and made the diagnosis difficult. At laparotomy, seven patients had resectable disease. Two patients had advanced disease so that no curative resection could be done. In one patient, a resection was technically impossible. A modified Whipple procedure (in which the pylorus is saved) is the method of choice for tumors of the second part of the duodenum. We perform a segmental resection for other tumors. In five patients, there was no involvement of the lymph nodes and these patients are well--two more than 30 months postoperatively and one patient almost ten years postoperatively. In two patients, one or more lymph nodes were involved, but they are still well 30 months postoperatively. As the prognosis of carcinoma of the duodenum, once metastasized, is poor, a greater awareness of the possibility of a duodenal tumor must accompany aggressive diagnostic and surgical procedures. That will be the only way to a higher percentage of cures.