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1.
World J Surg ; 39(1): 184-6, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25123174

ABSTRACT

BACKGROUND: Unilateral bloody nipple discharge (UBND) is mostly caused by benign conditions such as papilloma or ductal ectasia. However, in 7-33 % of all nipple discharge, it is caused by breast cancer. Conventional diagnostic imaging like mammography (MMG) and ultrasonography (US) is performed to exclude malignancy. Preliminary investigations of breast magnetic resonance imaging (MRI) assume that it has additional value. With an increasing availability of MRI, it is of clinical importance to evaluate this. We evaluated the additional diagnostic value of MRI in patients with UBND in the absence of a palpable mass, with normal conventional imaging. METHODS: All women with UBND in the period November 2007-July 2012 were included. In addition to the standard work-up (patient's history, physical examination, MMG, and US), MRI was performed. Data from these examinations and treatment were collected retrospectively. RESULTS: A total of 111 women (mean age 52 years; range 23-80) were included. In nine (8 %) patients, malignancy was suspected on MRI while conventional imaging was normal. In eight (89 %) of these patients, histology was obtained, two by core biopsy and six by terminal duct excision. Benign conditions were found in six patients (86 %) and a (pre-) malignant lesion in two patients. In both cases, it concerned a ductal carcinoma in situ, which was treated with breast-conserving therapy. Moreover, in two cases of (pre)malignancy, the MRI was interpreted as negative. CONCLUSION: In patients with UBND who show no signs of a malignancy on conventional diagnostic examinations, the added value of a breast MRI is limited, since a malignancy can be demonstrated in <2 %.


Subject(s)
Breast Diseases/diagnosis , Magnetic Resonance Imaging , Nipples/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma/diagnosis , Female , Humans , Mammography , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Ultrasonography, Mammary , Young Adult
2.
Ann Oncol ; 23(10): 2561-2566, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22495317

ABSTRACT

BACKGROUND: In the MIRROR study, pN0(i + ) and pN1mi were associated with reduced 5-year disease-free survival (DFS) compared with pN0. Nodal status (N-status) was assessed after central pathology review and restaging according to the sixth AJCC classification. We addressed the impact of pathology review. PATIENTS AND METHODS: Early favorable primary breast cancer patients, classified pN0, pN0(i + ), or pN1(mi) by local pathologists after sentinel node procedure, were included. We assessed the impact of pathology review on N-status (n = 2842) and 5-year DFS for those without adjuvant therapy (n = 1712). RESULTS: In all, 22% of the 1082 original pN0 patients was upstaged. Of the 623 original pN0(i + ) patients, 1% was downstaged, 26% was upstaged. Of 1137 patients staged pN1mi, 15% was downstaged, 11% upstaged. Originally, 5-year DFS was 85% for pN0, 74% for pN0(i + ), and 73% for pN1mi; HR 1.70 [95% confidence interval (CI) 1.27-2.27] and HR 1.57 (95% CI 1.16-2.13), respectively, compared with pN0. By review staging, 5-year DFS was 86% for pN0, 77% for pN0(i + ), 77% for pN1mi, and 74% for pN1 + . CONCLUSION: Pathology review changed the N-classification in 24%, mainly upstaging, with potentially clinical relevance for individual patients. The association of isolated tumor cells and micrometastases with outcome remained unchanged. Quality control should include nodal breast cancer staging.


Subject(s)
Breast Neoplasms/pathology , Female , Humans , Neoplasm Staging , Survival Rate
3.
Eur J Cancer ; 43(5): 867-76, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17307353

ABSTRACT

AIM OF THE STUDY: Results on tumour characteristics and survival of hereditary breast cancer (BC), especially on BRCA2-associated BC, are inconclusive. The prognostic impact of the classical tumour and treatment factors in hereditary BC is insufficiently known. METHODS: We selected 103 BRCA2-, 223 BRCA1- and 311 non-BRCA1/2 BC patients (diagnosis 1980-2004) from the Rotterdam Family Cancer Clinic. To correct for longevity bias, analyses were also performed while excluding index patients undergoing DNA testing 2 years after BC diagnosis. As a comparison group, 759 sporadic BC patients of comparable age at and year of diagnosis were selected. We compared tumour characteristics, the occurrence of ipsilateral recurrence (LRR) and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS) between these groups. By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in hereditary BC. RESULTS: We confirmed the presence of the particular BRCA1-phenotype. In contrast, tumour characteristics of BRCA2-associated BC were similar to those of non-BRCA1/2 and sporadic BC, with the exception of a high risk of CBC (3.1% per year) and oestrogen-receptor (ER)-positivity (83%). No significant differences between BRCA2-associated BC and other BC subgroups were found with respect to LRR, DDFS, BCSS and OS. Independent prognostic factors for BC-specific survival in hereditary BC (combining the three subgroups) were tumour stage, adjuvant chemotherapy, histologic grade, ER status and a prophylactic (salpingo-)oophorectomy. CONCLUSIONS: Apart from the frequent occurrence of contralateral BC and a positive ER-status, BRCA2-associated BC did not markedly differ from other hereditary or sporadic BC. Our observation that tumour size and nodal status are prognostic factors also in hereditary BC implies that the strategy to use these factors as a proxy for ultimate mortality appears to be valid also in this specific group of patients.


Subject(s)
Breast Neoplasms/genetics , Genes, BRCA1 , Genes, BRCA2 , Adult , Aged , Breast Neoplasms/mortality , Chi-Square Distribution , Cohort Studies , DNA, Neoplasm/analysis , Disease-Free Survival , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/mortality , Pedigree , Prognosis
4.
Br J Surg ; 93(8): 961-8, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16758466

ABSTRACT

BACKGROUND: A higher incidence of contralateral breast cancer and ipsilateral recurrence has been reported in familial breast cancer than in sporadic cancer. This study investigated the influence of contralateral cancer and tumour stage on survival in patients with familial non-BRCA1/BRCA2-associated breast cancer. METHODS: The incidences of contralateral breast cancer, ipsilateral recurrence, distant disease-free and overall survival were assessed in 327 patients from families with three or more breast and/or ovarian cancers, but no BRCA1 or BRCA2 gene mutation (familial non-BRCA1/2), and in 327 control subjects with sporadic breast cancer, matched for year and age at detection. RESULTS: Mean follow-up was 7.3 years for patients with familial-non-BRCA1/2 cancers and 6.5 years for patients with sporadic breast cancer. Tumours were stage T1 or lower in 62.1 per cent of familial non-BRCA1/2 cancers versus 49.9 per cent in sporadic breast cancers (P = 0.003), and node negative in 55.8 versus 52.1 per cent, respectively (P = 0.477). After 10 years the incidence of metachronous contralateral breast cancer was 6.4 per cent for familial non-BRCA1/2 tumours versus 5.4 per cent for sporadic cancers. The rate of ipsilateral recurrence was not significantly increased (17.0 versus 14.2 per cent, respectively, at 10 years; P = 0.132). Tumour size (hazard ratio (HR) 1.02 per mm increase, P = 0.016) and node status (HR 2.6 for three or more involved nodes versus node negative, P = 0.017) were independent predictors of overall survival in the familial non-BRCA1/2 group, and in the whole group, whereas contralateral breast cancer (HR 0.7, P = 0.503) and risk-reducing contralateral mastectomy (HR 0.4, P = 0.163) were not. CONCLUSION: Stage at detection was a key determinant of prognosis in familial non-BRCA1/2 breast cancer, whereas contralateral cancer was not. Risk-reducing contralateral mastectomy did not significantly improve survival, but early detection can. Decisions on breast-conserving treatment can be made on the same grounds in patients with familial and sporadic breast cancer.


Subject(s)
Breast Neoplasms/genetics , Neoplasms, Second Primary/genetics , Adult , Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Disease-Free Survival , Female , Humans , Mastectomy, Segmental/methods , Middle Aged , Neoplasm Staging , Neoplasms, Second Primary/diagnosis , Neoplasms, Second Primary/surgery , Pedigree , Prognosis , Risk Factors , Survival Analysis
5.
Eur J Surg Oncol ; 32(3): 282-6, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16439094

ABSTRACT

AIM: To report the long-term results of sentinel node negative breast cancer patients treated without axillary lymph node dissection and the 5-year follow-up results of 149 patients. METHODS: The incidence of axillary-and local recurrences and second ipsilateral primary tumours was evaluated. The added value of annual ultrasound of the treated axilla, being part of the standard follow-up, was also evaluated. RESULTS: After a mean follow-up of 65 months (50-79) axillary recurrences were observed in four patients, local recurrences or ipsilateral second primary tumours were diagnosed in another seven patients. All axillary recurrences were diagnosed because of a palpable axillary mass; ultrasound in combination with fine needle aspiration cytology did not have an added value. CONCLUSION: It can be concluded that the incidence of axillary recurrences after negative SN is much lower than expected. There is no added value of US and FNAC of the axilla in the routine follow-up of SN negative patients.


Subject(s)
Breast Neoplasms/pathology , Sentinel Lymph Node Biopsy , Adult , Aged , Aged, 80 and over , Axilla , Biopsy, Fine-Needle , Female , Follow-Up Studies , Humans , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymphatic Metastasis , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Time Factors , Ultrasonography
6.
Ann Oncol ; 17(3): 391-400, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16322115

ABSTRACT

BACKGROUND: Studies comparing survival in BRCA1-associated and sporadic breast cancer (BC) report inconsistent results and frequently concern small sample sizes. Further, the prognostic impact of the classical tumour and treatment factors is unclear in BRCA1-associated BC. PATIENTS AND METHODS: We selected 223 BC patients diagnosed between 1980 and 2001 within families with a deleterious germline BRCA1-mutation ascertained at the Rotterdam Family Cancer Clinic. To correct for ascertainment bias, the group of index patients undergoing DNA testing more than 2 years after BC diagnosis (n = 53) was separated from the other BRCA1-patients (n = 170). All BRCA1-associated patients were matched in a 1:2 ratio for age and year of diagnosis to sporadic BC patients. We compared the occurrence of ipsi- and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS). By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in BRCA1-associated and sporadic breast cancers. RESULTS: For the total group of 669 cases, the median follow-up was 5.1 years, the median age at diagnosis 39 years. We confirmed the existence of the typical BRCA1-associated tumour type and the high CBC incidence. No significant differences between BRCA1-associated and sporadic tumours were found with respect to ipsilateral BC recurrence (HR(mult) 0.7; P = 0.24), DDFS (HR(mult) 1.2; P = 0.37) or BC-specific survival (HR(mult) 1.3; P = 0.23). A trend towards a worse survival was found for BRCA1-associated ductal BC (HR(mult) 1.5, P = 0.07). Prognostic factors for BRCA1-associated BC were age at diagnosis, tumour size and morphology, and nodal status. Further, survival was non-significantly improved by systemic treatment and a bilateral salpingo-oophorectomy. No effect on survival of a contralateral prophylactic mastectomy was seen. CONCLUSIONS: BRCA1-associated BC is characterised by specific tumour characteristics, a high incidence of CBC and a trend towards a worse survival for the ductal tumour type. Our observation that tumour size and nodal status are also prognostic factors for BRCA1-associated BC implies that the strategy to use these factors as a proxy for ultimate mortality, for instance in BC screening programmes or the consideration of (contralateral) preventive mastectomy, appears to be valid in this specific group of patients.


Subject(s)
Breast Neoplasms/genetics , Genes, BRCA1 , Prognosis , Survival Analysis , Female , Humans
7.
Ned Tijdschr Geneeskd ; 149(48): 2663-7, 2005 Nov 26.
Article in Dutch | MEDLINE | ID: mdl-16358615

ABSTRACT

Preventive surgical procedures for inherited risk of breast cancer Forwomen with a demonstrated BRCA1 or BRCA2 mutation, the cumulative risk of developing invasive breast cancer before the age of 70 years is about 50-85% and the risk of developing invasive epithelial ovarian cancer is 20-60%. Regular surveillance including physical examination and imaging is offered to mutation carriers and the options for risk-reducing surgery are discussed. Although bilateral prophylactic mastectomy is a drastic intervention, it significantly reduces the incidence of breast cancer. For mutation carriers with breast cancer, the decision to combine risk-reducing surgery with treatment is determined by the TNM stage of the disease. Prophylactic bi- or contralateral mastectomy after previous treatment for unilateral breast cancer reduces the incidence of contralateral breast cancer, but has no impact on survival. The complexity of the problem demands a multidisciplinary approach within the context of a family cancer clinic.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/prevention & control , Mastectomy , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Female , Genetic Predisposition to Disease , Humans , Mutation , Risk Factors , Risk Management
8.
J Biomed Opt ; 9(6): 1129-36, 2004.
Article in English | MEDLINE | ID: mdl-15568932

ABSTRACT

We use spatially resolved diffuse remittance spectroscopy (DRS) for the measurement of absorption (mu(a)) and reduced scattering (mu(s)') coefficients of normal and malignant breast tissue in vivo during surgery. Prior to these measurements, the linearity of the measurement technique was evaluated on liquid optical phantoms. In addition, the reproducibility of in-vivo tissue measurements was determined on a healthy volunteer. We present results of the in-vivo measurement of optical properties in the wavelength range from 600 to 1100 nm performed during radical mastectomy. A total of 24 patients were included in the study. Both the absorption and reduced scattering properties show large variations. Significant differences in optical properties between normal (glandular plus lipid rich tissue) and tumor tissues are present in 74% of all patients. However, in some cases the tumor showed lower values than normal tissue, and in other cases this was the other way around. Thus, a general trend in optical properties is not observed. However, the average absorption contrast of all patients as a function of wavelength reveals an optimal contrast peak at 650 nm. We believe that this relates to a difference in vascular saturation between tumor and adjacent normal tissue.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/physiopathology , Breast/pathology , Breast/physiopathology , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Tomography, Optical/methods , Female , Humans , Intraoperative Period/methods , Mammography/instrumentation , Mammography/methods , Phantoms, Imaging , Reproducibility of Results , Sensitivity and Specificity , Spectrum Analysis/instrumentation , Spectrum Analysis/methods , Tomography, Optical/instrumentation
9.
Eur J Cancer ; 40(8): 1150-8, 2004 May.
Article in English | MEDLINE | ID: mdl-15110878

ABSTRACT

The overall rate of an ipsilateral breast tumour recurrence (IBTR) after breast-conserving therapy (BCT) ranges from 1% to 2% per year. Risk factors include young age but data on the impact of BRCA1/2 mutations or a definite positive family history for breast cancer are scarce. We investigated IBTR after BCT in patients with hereditary breast cancer (HBC). Through our family cancer clinic we identified 87 HBC patients, including 26 BRCA1/2 carriers, who underwent BCT between 1980 and 1995 (cases). They were compared to 174 patients with sporadic breast cancer (controls) also treated with BCT, matched for age and year of diagnosis. Median follow up was 6.1 years for the cases and 6.0 years for controls. Patient and tumour characteristics were similar in both groups. An IBTR was observed in 19 (21.8%) hereditary and 21 (12.1%) sporadic patients. In the hereditary patients more recurrences occurred elsewhere in the breast (21% versus 9.5%), suggestive of new primaries. Overall, the actuarial IBTR rate was similar at 2 years, but higher in hereditary as compared to sporadic patients at 5 years (14% versus 7%) and at 10 years (30% versus 16%) (P=0.05). Post-relapse and overall survival was not different between hereditary and sporadic cases. Hereditary breast cancer was therefore associated with a higher frequency of early (2-5 years) and late (>5 years) local recurrences following BCT. These data suggest an indication for long-term follow up in HBC and should be taken into account when additional 'risk-reducing' surgery after primary BCT is eventually considered.


Subject(s)
Breast Neoplasms/surgery , Mastectomy, Segmental/methods , Mutation/genetics , Neoplasms, Second Primary , Adult , Aged , Breast Neoplasms/genetics , Cohort Studies , Disease-Free Survival , Female , Genes, BRCA1 , Genes, BRCA2 , Genetic Predisposition to Disease , Humans , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Proportional Hazards Models , Risk Factors
10.
Eur J Cancer ; 39(2): 170-4, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12509948

ABSTRACT

Currently, axillary lymph node dissection is increasingly being replaced by the sentinel node procedure. This method is time-consuming and the full immunohistochemical evaluation is usually only first known postoperatively. This study was designed to evaluate the accuracy of preoperative ultrasound-guided fine needle aspirations (FNAs) for the detection of non-palpable lymph node metastases in primary breast cancer patients. We evaluated the material of 183 ultrasound-guided FNAs of non-palpable axillary lymph nodes of primary breast cancer patients. The cytological results were compared with the final histological diagnosis. Ultrasound-guided FNA detected metastases in 44% (37/85) of histologically node-positive patients, in 20% of the total patient population studied. These pecentages are likely to be higher when women with palpable nodes are included. Cytologically false-negative and false-positive nodes were seen in 28 (15%) and three cases (1.6%), respectively. Interestingly 25% (n=7) of the false-negative nodes, revealed micrometastases on postoperative histology. The sensitivity was 57%, the specificity 96%. We conclude that ultrasound-guided FNA of the axillary lymph nodes is an effective procedure that should be included in the preoperative staging of all primary breast cancer patients. Whether lymph nodes are palpable or not, it will save considerable operating time by selecting those who need a complete axillary lymph node dissection at primary surgery and would save a significant number of sentinel lymph node dissections (SLNDs).


Subject(s)
Biopsy, Needle/methods , Breast Neoplasms/pathology , Female , Humans , Lymphatic Metastasis/pathology , Sensitivity and Specificity , Ultrasonography, Interventional
11.
J Clin Pathol ; 55(12): 932-5, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12461062

ABSTRACT

AIMS: It has been suggested that patients with T1-2 breast tumours and sentinel node (SLN) micrometastases, defined as foci of tumour cells smaller than 2 mm, may be spared completion axillary lymph node dissection because of the low incidence of further metastatic disease. To gain insight into the extent of non-sentinel lymph node (n-SLN) involvement, SLNs and complementary axillary clearance specimens in patients with SLN micrometastases were examined. METHODS: A set of 32 patients with SLN micrometastases was selected on the basis of pathology reports and review of SLNs. Five hundred and thirteen n-SLNs from the axillary clearance specimens were serially sectioned and analysed by means of immunohistochemistry for metastatic disease. Lymph node metastases were grouped as macrometastases (> 2 mm), and micrometastases (< 2 mm), and further subdivided as isolated tumour cells (ITCs) or clusters. RESULTS: In 11 of 32 patients, one or more n-SLN was involved. Grade 3 tumours and tumours > 2 cm (T2-3 v T1) were significantly associated with n-SLN micrometastases as clusters (grade: odds ratio (OR), 8.3; 95% confidence interval (CI), 1.4 to 50.0; size: T2-3 tumours v T1: OR, 15; 95% CI, 2.18 to 103.0). However, no subgroup of tumours with regard to size and grade was identified that did not have n-SLN metastases. CONCLUSIONS: In patients with breast cancer and SLN micrometastases, n-SLN involvement is relatively common. The incidence of metastatic clusters in n-SLN is greatly increased in patients with T2-3 tumours and grade 3 tumours. Therefore, axillary lymph node dissection is especially warranted in these patients. However, because n-SLN metastases also occur in T1 and low grade tumours, even these should be subjected to routine axillary dissection to achieve local control.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/secondary , Sentinel Lymph Node Biopsy , Axilla , Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , Carcinoma, Ductal, Breast/chemistry , Carcinoma, Lobular/chemistry , Female , Humans , Keratins/analysis , Lymph Node Excision , Lymphatic Metastasis , Neoplasm Staging
12.
N Engl J Med ; 345(3): 159-64, 2001 Jul 19.
Article in English | MEDLINE | ID: mdl-11463009

ABSTRACT

BACKGROUND: Women with a BRCA1 or BRCA2 mutation have a high risk of breast cancer and may choose to undergo prophylactic bilateral total mastectomy. We investigated the efficacy of this procedure in such women. METHODS: We conducted a prospective study of 139 women with a pathogenic BRCA1 or BRCA2 mutation who were enrolled in a breast-cancer surveillance program at the Rotterdam Family Cancer Clinic. At the time of enrollment, none of the women had a history of breast cancer. Seventy-six of these women eventually underwent prophylactic mastectomy, and the other 63 remained under regular surveillance. The effect of mastectomy on the incidence of breast cancer was analyzed by the Cox proportional-hazards method in which mastectomy was modeled as a time-dependent covariate. RESULTS: No cases of breast cancer were observed after prophylactic mastectomy after a mean (+/-SE) follow-up of 2.9+/-1.4 years, whereas eight breast cancers developed in women under regular surveillance after a mean follow-up of 3.0+/-1.5 years (P=0.003; hazard ratio, 0; 95 percent confidence interval, 0 to 0.36). The actuarial mean five-year incidence of breast cancer among all women in the surveillance group was 17+/-7 percent. On the basis of an exponential model, the yearly incidence of breast cancer in this group was 2.5 percent. The observed number of breast cancers in the surveillance group was consistent with the expected number (ratio of observed to expected cases, 1.2; 95 percent confidence interval, 0.4 to 3.7; P=0.80). CONCLUSIONS: In women with a BRCA1 or BRCA2 mutation, prophylactic bilateral total mastectomy reduces the incidence of breast cancer at three years of follow-up.


Subject(s)
Breast Neoplasms/prevention & control , Genes, BRCA1 , Mastectomy, Simple , Neoplasm Proteins/genetics , Transcription Factors/genetics , Adult , BRCA2 Protein , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Breast Neoplasms/surgery , Female , Humans , Middle Aged , Mutation , Proportional Hazards Models , Prospective Studies
13.
Ned Tijdschr Geneeskd ; 144(37): 1761-3, 2000 Sep 09.
Article in Dutch | MEDLINE | ID: mdl-11004947

ABSTRACT

Three women, two aged 63 and one aged 47 years, developed serious abdominal pains and nausea during and/or years after treatment for metastasized lobular mammary carcinoma. These symptoms were due to jejunal tumour with perforation, sigmoid and hepatic metastases and perforated gastric metastases, respectively. After surgical treatment of the affected part of the gastrointestinal tract, the patients survived for a number of months without abdominal symptoms. Infiltrating lobular mammary carcinoma is more often associated with gastrointestinal metastases than infiltrating ductal mammary carcinoma. Progressive abdominal symptoms attributable to such metastases constitute an indication for a change of the systemic treatment. In case of insufficient effect of this treatment, and in acute situations, surgical treatment may result in protracted palliation.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Lobular/secondary , Carcinoma, Lobular/surgery , Gastrointestinal Neoplasms/secondary , Gastrointestinal Neoplasms/surgery , Abdominal Pain/etiology , Disease-Free Survival , Female , Humans , Middle Aged , Nausea/etiology , Palliative Care , Retrospective Studies , Treatment Outcome
14.
Cancer Genet Cytogenet ; 90(2): 109-17, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8830718

ABSTRACT

We performed flow cytometry and cytogenetic analysis of 37 adenocarcinomas of the distal esophagus and cardia, of which 22 arose in Barrett's mucosa. Two of eight analyzed specimens of Barrett's mucosa had clonal chromosomal abnormalities. In 19 cases clonal chromosomal abnormalities were found in tumor tissue. The complex pattern of cytogenetic changes did not differ among the adenocarcinomas arisen in Barrett's esophagus, and those in the distal esophagus without Barrett's mucosa or cardia. Abnormal karyotypes with multiple and complex rearrangements were seen in 11 cases and with single or a few numeric changes in eight. Losses of chromosomes 4, 18, 21, and Y were the most frequent numeric changes. Loss of the Y chromosome was observed in eight of 26 tumors of males (31%). Gains of chromosomes 14 and 20 were also frequent numeric changes. Structural abnormalities were observed in 13 of the abnormal karyotypes (68%). The chromosome arms most frequently rearranged were 1p, 3q, 11p and 22p. The chromosome arm most frequently contributing to losses was 1p, with the shortest region of overlap being 1p22-33. The chromosome arms most often involved in gains were 11p and 22p, and i(3q) was the isochromosome that was most frequently identified.


Subject(s)
Adenocarcinoma/genetics , Barrett Esophagus/genetics , Chromosome Aberrations , Chromosome Deletion , Chromosome Disorders , Esophageal Neoplasms/genetics , Esophagus/pathology , Stomach Neoplasms/genetics , Adenocarcinoma/pathology , Aged , Barrett Esophagus/pathology , Cardia , Chromosome Mapping , Esophageal Neoplasms/pathology , Female , Flow Cytometry , Humans , Karyotyping , Male , Middle Aged , Mucous Membrane/pathology , Neoplasm Staging , Sex Chromosome Aberrations , Stomach Neoplasms/pathology , Y Chromosome
16.
Hepatogastroenterology ; 42(6): 786-8, 1995.
Article in English | MEDLINE | ID: mdl-8847023

ABSTRACT

BACKGROUND/AIMS: The role of DNA ploidy of tumor cells as a prognostic factor for survival after resection was evaluated in 40 patients with an adenocarcinoma in Barrett's esophagus (28 men and 12 women; mean age, 61 years). MATERIALS AND METHODS: After resection of the esophagus, staging was performed according to the TNM-classification (UICC 1987). Tumor tissue specimens were reviewed for the histological differentiation grade and flow cytometry was performed on paraffin embedded tissue according to the method described by Hedley. RESULTS: There was no significant correlation between DNA-ploidy and TNM-stage or histological differentiation grade of the tumor. DNA ploidy, stage and grade as prognostic factors for the survival were evaluated by multivariate analysis. DNA ploidy significantly (p= 0.04) correlated with survival, also univariately. Patients with diploid tumors had 3- and 5-year survival rates of 51% and 25% respectively, as compared to 10% and 0% respectively for patients with aneuploid or tetraploid/increased G2 tumors. CONCLUSION: DNA ploidy is an independent prognostic factor for the survival of patients with an adenocarcinoma in Barrett's esophagus.


Subject(s)
Adenocarcinoma/genetics , Barrett Esophagus/complications , DNA, Neoplasm/genetics , Esophageal Neoplasms/genetics , Adenocarcinoma/complications , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Esophageal Neoplasms/complications , Esophageal Neoplasms/mortality , Esophageal Neoplasms/surgery , Female , Flow Cytometry , Humans , Male , Middle Aged , Multivariate Analysis , Ploidies , Prognosis , Survival Analysis
17.
Gut ; 35(10): 1348-51, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7959183

ABSTRACT

The role of dysplasia and aneuploidy as markers in columnar epithelium for malignant degeneration in Barrett's oesophagus was compared in a case control study comprising 38 patients with benign Barrett's oesophagus and 50 patients with Barrett's oesophagus associated with adenocarcinoma. Tissue specimens of columnar epithelium were reviewed for the presence of specialised columnar epithelium and the grade of dysplasia. Ploidy was determined using the method for formalin fixed paraffin wax embedded tissue described by Hedley. There was no significant difference in the frequency of specialised columnar epithelium between both groups. Dysplasia was found more often in columnar epithelium associated with adenocarcinoma compared with benign Barrett's oesophagus (p < 0.001). Multivariate analysis using logistic regression showed an increased risk of malignancy in Barrett's oesophagus in case of dysplasia (odds ratio 9.4, p = 0.003 for mild dysplasia and 33.1, p < 0.001 for moderate or severe dysplasia). Ploidy was not statistically significantly correlated with dysplasia. Aneuploidy or increased G2/tetraploidy proved to be an independent risk factor for younger patients (age < 65 years: odds ratio 44.7, p = 0.003). In conclusion, dysplasia and aneuploidy or increased G2/tetraploidy in columnar epithelium are independent risk factors for malignant degeneration. Patients with these risk factors should be offered a more intensive screening programme.


Subject(s)
Barrett Esophagus/pathology , Esophageal Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Aneuploidy , Barrett Esophagus/genetics , Biomarkers , Esophageal Neoplasms/genetics , Female , Humans , Male , Middle Aged , Multivariate Analysis
18.
Cancer ; 72(4): 1155-8, 1993 Aug 15.
Article in English | MEDLINE | ID: mdl-8339208

ABSTRACT

BACKGROUND: To evaluate the importance of the length of columnar-lined esophagus, sex, age, smoking, and drinking habits as risk factors for malignant degeneration, the authors performed a retrospective case-control study comparing patients with and without adenocarcinoma in Barrett esophagus. METHODS: The records of 96 patients (53 male and 43 female; mean age, 61 years) with a benign columnar-lined esophagus and 62 patients (47 male and 15 female; mean age, 62 years) with an adenocarcinoma in columnar-lined esophagus referred to the Rotterdam Esophageal Tumor Study Group, diagnosed over the same period (1978-1985), were reviewed. A frequency distribution of the length of columnar-lined esophagus in both groups was made. Statistical analysis was performed with multivariate methods. RESULTS: The length of columnar-lined esophagus was related significantly to carcinoma: a doubling of the length resulted in a 1.7 times increased risk. Smokers had a 2.3-fold increased risk as compared with nonsmokers. Male sex as a risk factor approached statistical significance (P = 0.06). Adjusted for these risk factors, no relation between carcinoma and age or alcohol consumption was found. CONCLUSIONS: The risk of development of an adenocarcinoma in Barrett esophagus increased with the length of Barrett epithelium. Smoking and possibly male sex were also risk factors. The identification of these risk factors may help in developing more efficient screening programs for patients with Barrett esophagus.


Subject(s)
Adenocarcinoma/etiology , Barrett Esophagus/complications , Esophageal Neoplasms/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Alcohol Drinking/adverse effects , Barrett Esophagus/pathology , Case-Control Studies , Esophagus/pathology , Female , Humans , Male , Middle Aged , Mucous Membrane/pathology , Odds Ratio , Retrospective Studies , Risk Factors , Sex Factors , Smoking/adverse effects
19.
Gut ; 33(11): 1454-8, 1992 Nov.
Article in English | MEDLINE | ID: mdl-1452066

ABSTRACT

A retrospective study was performed of an 11 year period (1978-88) to analyse the survival of 112 patients (85 men and 27 women, mean age 63 years) with adenocarcinoma in a columnar lined (Barrett's) oesophagus in respect of surgical treatment, tumour staging, and histological grading. Presenting symptoms were dysphagia (60%) and pain (25%). Only six patients were previously known to have a columnar lined oesophagus. Eighty five patients (76%) underwent partial resection of the oesophagus and cardia. Postoperative mortality was 6%. After resection (n = 85), the 5 year survival was 24%. Survival was significantly better for patients without regional lymph node metastases (stage 0, I, IIA (n = 61): 5 year survival 30%) and even better if the tumour was restricted to the submucosa (stage 0, I (n = 12): 5 year survival 63%). Survival was not influenced by the histological grade of the tumour. Staging based on infiltration of the oesophageal wall and lymph node spread is valuable in determining the prognosis for patients with adenocarcinoma in Barrett's oesophagus.


Subject(s)
Adenocarcinoma/surgery , Barrett Esophagus/surgery , Esophageal Neoplasms/surgery , Esophagus/surgery , Adenocarcinoma/complications , Adenocarcinoma/pathology , Barrett Esophagus/complications , Barrett Esophagus/pathology , Cardia/surgery , Esophageal Neoplasms/complications , Esophageal Neoplasms/pathology , Esophagus/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Survival Rate , Treatment Outcome
20.
Hepatogastroenterology ; 39(5): 429-32, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1459525

ABSTRACT

In order to analyze the results of treatment of patients with locoregional recurrence after intentional curative resection of pancreatic cancer, a retrospective study was performed. During the period 1978-1988, 108 patients underwent an intentional curative resection fo the pancreas. In 34 patients locoregional recurrence occurred, all within a period of three years (cumulative recurrence rate 56%). Sixty-eight percent of the patients presented with upper abdominal pain, and 62% with weight loss. Survival was significantly better (p = 0.02) in the group of 18 patients without distant metastases (1-year survival 22%) than in the 16 patients with distant metastases (1-year survival 0%). Five patients without proven distant metastases were treated by resection or chemotherapy. The mean survival was 33 months (range 6-74) in the treated group, and 4 months (0.4-7 months) in the untreated group, p = 0.002. In this retrospective study the longest survival was seen after radical resection of locoregional tumor recurrence. We therefore recommend that patients with locoregional recurrence without distant metastases after intentional curative resection of pancreatic cancer be treated.


Subject(s)
Neoplasm Recurrence, Local/surgery , Pancreatic Neoplasms/surgery , Adult , Aged , Female , Humans , Incidence , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Pancreatic Neoplasms/pathology , Retrospective Studies , Survival Rate
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