Is the sentinel lymph node pathology protocol in breast cancer patients associated with the risk of regional recurrence?

BACKGROUND: Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN) in breast cancer patients. Previously, we reported that ultra-staging led to more axillary lymph node dissections (ALND). The question was, whether ultra-staging is effective in reducing the risk of regional relapse. METHODS: From January 2002 to July 2003, 541 patients from 4 hospitals were prospectively registered when they underwent a SN biopsy. In hospitals A, B, and C, 3 levels of the SN were examined pathologically, whereas in hospital D at least 7 additional levels were examined. Patients with a positive SN, including isolated tumor cells, underwent an ALND. This analysis focuses on the 341 patients with a negative SN. Primary endpoint was 5-year regional recurrence rate. RESULTS: In hospital D 34% of the patients had a negative SN as compared to 71% in hospitals A, B, and C combined (p < 0.001). At 5 years follow-up, 9 (2.6%) patients had developed a regional lymph node relapse. In hospital D none of the patients had a regional recurrence, as compared to 9 (2.9%) cases of recurrence in hospitals A, B, and C. CONCLUSION: The less intensified SN pathology protocol appeared to be associated with a slightly increased risk of regional recurrence. The absolute risk was still less than 3%, and does not seem to justify the intensified SN pathology protocol of hospital D.

Conclusiveness of fine needle aspiration in 2419 histologically confirmed benign and malignant breast lesions.

We aimed to retrospectively assess (1) the conclusiveness of breast fine needle aspiration (FNA) in a histologically confirmed population and (2) the clinical and radiologic determinants of a conclusive diagnosis. Aspirates were diagnosed as inadequate, benign, atypical, suspicious or malignant. We defined a conclusive FNA diagnosis as 'benign' in histologically benign lesions and as 'malignant' in histologically malignant lesions. In 2419 breast lesions, the proportion of conclusive diagnoses was 46.1% (95% confidence interval, 42.0-50.2%) in histologically benign lesions (n = 571) and 81.6% (95% confidence interval, 79.8%-83.4%) in histologically malignant lesions (n = 1848). On multivariate analysis, factors associated with a conclusive preoperative diagnosis included tumour diameter of 2-2.9 cm (P < 0.001), malignant histology (P < 0.001) and the pathologist examining the aspirate (P = 0.02). Breast FNA has to be utilised selectively in the routine work-up of breast lesions. In suspicious lesions of large size, FNA may still be used to obtain a quick confirmation of malignancy.

Preoperative cytological and histological diagnosis of breast lesions: A critical review.

BACKGROUND: Non-operative pathology diagnoses constitute an essential part of the work-up of breast lesions. With fine needle aspiration (FNA) and core needle biopsy (CNB) both having unique advantages, there is an increasing acceptance of CNB. This paper aims to outline the scientific basis of this trend. Additionally, we provide an update on novel techniques that derive cytological specimens from CNB (i.e., touch imprint (TI) and core wash (CW) cytology) in an attempt to get the best of both worlds. METHODS: In addition to using the authors' experience, we performed a search of the Medline database combining the search terms "breast cancer diagnosis", "core needle biopsy", "fine needle aspiration", "touch imprint cytology", "core wash cytology" and "complications". We defined a conclusive non-operative diagnosis as "malignant" in lesions that were malignant on follow-up and "benign" in lesions that were benign on follow-up. RESULTS: CNB was more often conclusive than FNA in benign and malignant lesions in 4 prospective studies. Although the more rapid diagnoses by FNA result in less patient anxiety during diagnostic work-up, CNB allows for fairly reliable estimation of invasion, histological type, grade, and receptor expression. CW and TI cytology seem promising techniques with conclusiveness rates that are roughly comparable to that of FNA. CONCLUSIONS: All new suspicious breast lesions require careful non-operative investigation by CNB. However, additional cytological assessment by FNA can still be useful as a same-day diagnosis decreases patient anxiety and facilitates surgical treatment planning. TI and CW cytology techniques are promising same-day diagnosis modalities.

The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast.

Re-excision rates after breast conserving surgery(BCS) of invasive lobular carcinoma (ILC) are high.Preoperative breast MRI has the potential to reduce re-excision rates, but may lead to an increased rate of mastectomies. Hence, we assessed the influence of preoperative breast MRI on the re-excision rate and the rate of mastectomies. We performed a retrospective cohort study of a consecutive series of patients with ILC who presented in one of two dedicated tertiary cancer centers between 1993 and 2005. We assessed the initial type of surgery(BCS or mastectomy), the re-excision rate and the final type of surgery. Patients were stratified into two groups:those who received preoperative MRI (MR? group) and those who did not (MR- group). In the MR- group, 27%of the patients underwent a re-excision after initial BCS. In the MR? group, this rate was significantly lower at 9%.The odds ratio was 3.64 (95% CI: 1.30-10.20, P = 0.010).There was a trend towards a lower final mastectomy rate in the MR? group compared to the MR- group (48 vs. 59%,P = 0.098). In conclusion, preoperative MRI in patients with ILC can reduce re-excision rates without increasing the rate of mastectomies.

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma.

AIM: To determine whether -1195 A-->G and/or -765 G-->C polymorphisms in Cyclooxygenase-2 (COX-2) may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS: Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. RESULTS: The distribution of the -1195 A-->G polymorphism was significantly different in esophageal cancer patients compared to controls. The -1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma (OR = 3.85, 95% CI: 1.45-10.3) compared with the -1195 AA genotype as a reference. The -765 G-->C genotype distribution was not different between the two groups. The GG/GG haplotype was present more often in esophageal adenocarcinoma patients than in controls (OR = 3.45, 95% CI: 1.24-9.58; with AG/AG as a reference). The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical significance. CONCLUSION: Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.

Hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa is a chronic, recurrent, suppurative cutaneous disease. Despite its incidence, optimal medical or surgical treatment remains unclear. This review describes the disease, ranging from pathogenesis to treatment and prognosis. METHODS: Articles were sourced from PubMed and Medline, using the MeSH terms 'hidradenitis suppurativa' and 'acne inversa'. Selection of articles was based on peer review, journal, relevance and English language. RESULTS AND CONCLUSION: On the basis of histological findings, the disease is now considered inflammatory and originating from the hair follicle; therefore, the term 'acne inversa' is favoured by some experts. The exact aetiology remains obscure but smoking seems to be a major triggering factor. Treatment should be individualized according to the site and extent of the disease. Absolute cessation of smoking is essential in the treatment of hidradenitis. Management with antibiotics or other medications may relieve early symptoms, but radical surgery may be necessary for control and to prevent recurrence.

The value of MRI compared to mammography in the assessment of tumour extent in invasive lobular carcinoma of the breast.

AIMS: Invasive lobular carcinoma of the breast (ILC) is known to be substantially underestimated by mammography, which makes correct planning of treatment difficult. MRI has been proposed as a valuable adjunct to mammography. The purpose of the current study is to evaluate its value, compare it to mammography and assess the possible causes of over- and underestimation of lesion size on MRI. METHOD: The mammograms and MRI scans of 67 consecutive patients with ILC were retrieved and re-evaluated. Size measurements were correlated to the sizes extracted from the pathology report. RESULTS: MRI measurements correlated better to pathologic size (r=0.85) than mammographic measurements (r=0.27). Underestimation of tumour size was more common on mammography (p<0.001); overestimation occurred with equal frequency (p=0.69). Overestimation on MRI, caused by non-malignant findings, was attributed to enhancing lobular carcinoma in situ. CONCLUSION: MRI is a more accurate modality for determining tumour size in patients with ILC than mammography. The typical underestimation of lesion size by mammography can be prevented with the aid of MRI, without increasing the risk of lesion overestimation.

[Hepatocellular adenoma, a tumour particularly seen in mostly young women]. / Het leverceladenoom, een tumor bij veelal jonge vrouwen.

A 37-year-old woman was examined because of temporary diarrhoea. On CT scan, there was an abnormality of the liver. MRI showed a tumour that was suspicious for adenoma. Biopsy confirmed the diagnosis of hepatocellular adenoma. The patient then discontinued the use of oral contraceptives. The tumour regressed and was resected after two years. A 22-year-old woman presented with abdominal pain. A tumour was found in the upper right quadrant of the abdomen. In the laboratory, liver function tests were abnormal. Ultrasound and a CT scan of the liver showed an adenoma. After withdrawal of oral contraceptives, abdominal complaints lessened, but no regression of the tumour was detected. Surgical resection was uncomplicated. Hepatocellular adenoma is a rare, benign tumour of the liver, most often seen in young healthy women. Its incidence is rising due to the prolonged use of oral contraceptives. Not rarely, benign liver tumours are incidental findings on echography. If symptomatic, the presentation usually consists of vague abdominal complaints. Spontaneous rupture and malignant degeneration have been reported for adenoma. A reliable diagnosis is mandatory for the decision whether to apply surgery or continue observation. Radiological investigations play a key role in the detection and diagnosis of hepatocellular adenoma. Due to the risk of bleeding and malignant degeneration, elective surgical resection is indicated in symptomatic adenomas, asymptomatic adenomas larger than 5 cm in diameter, and smaller adenomas without regression after discontinuation of oral contraceptives.

Quality of life after surgical treatment of colorectal liver metastases.

BACKGROUND: The surgical approach to colorectal liver metastases is becoming increasingly aggressive. The aim of this prospective study was to evaluate the impact of surgery on health-related quality of life (HRQoL) of patients with colorectal liver metastases. METHODS: HRQoL data from 97 patients with colorectal liver metastases were analysed. Sixty patients (group 1) had surgical treatment of the liver metastases. Seventeen patients (group 2) were shown to have inoperable disease at laparotomy. Twenty outpatients with inoperable disease were included as a control group (group 3). Two validated HRQoL instruments, the European Organization for Research and Treatment of Cancer Core questionnaire (QLQ C-30) and the EuroQol-5D, were applied. RESULTS: By 2 weeks after operation patients in group 1 showed a clear overall deterioration in HRQoL, but after 3 months most HRQoL scores had returned to baseline levels. At 2 weeks after surgery there was clear deterioration in almost all HRQoL domains in group 2, and several symptoms were still being reported at 3 months. Patients in group 3 showed hardly any deterioration in HRQoL over the 3 months. CONCLUSION: The fast recovery of HRQoL, generally within 3 months, justifies an aggressive surgical approach to colorectal liver metastases. However, careful preoperative evaluation is crucial to avoid needless laparotomy, considering the ongoing deteriorated HRQoL of group 2.

[The great important of tumor-free margins in the breast-saving procedure]. / Het grote belang van tumorvrije snijvlakken bij de borstsparende behandeling.

There is increasing evidence that local recurrence after breast-conserving surgery may lead to an increase in distant metastases and disease-specific mortality. The most important factor responsible for recurrence is the margin status after excision. The treatment of patients with breast cancer should be decided upon by a multidisciplinary treatment group so that the candidates for a breast-conserving procedure can be adequately selected with emphasis on achieving maximum local control.

Impact of [18F]fluorodeoxyglucose positron emission tomography on surgical management of melanoma patients.

BACKGROUND: Several studies have shown adequate sensitivity and specificity of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the detection of metastases from melanoma, but few have addressed its impact on treatment. The aim of this retrospective study was to assess the impact of FDG-PET on treatment of melanoma in three Dutch university medical centres. METHODS: The medical records of 257 patients were reviewed. The indications for FDG-PET and findings were recorded. Unexpected findings of suspected (pre)malignant tumours other than melanoma were assessed. Treatment plans before and after FDG-PET were recorded and analysed to evaluate changes in disease management. RESULTS: Most scans (71.2 per cent) were requested for staging, mainly to detect distant metastases in patients with stage III disease. Overall, 56 patients (21.8 per cent) were upstaged as a result of PET. In 44 patients (17.1 per cent) treatment was changed, usually from surgery to systemic treatment in patients with stage III disease. Unexpected tumours were detected (mainly colorectal) in 11 patients (4.3 per cent). CONCLUSION: FDG-PET is most valuable in patients with stage III melanoma for detection of distant metastases and identification of candidates for surgery and/or systemic treatment. Unexpected FDG-PET findings should not be disregarded, as (pre)malignant, clinically relevant, tumours may be identified.

Cost-effectiveness of new guidelines for adjuvant systemic therapy for patients with primary breast cancer.

BACKGROUND: In this study, the potential impact of a new national guideline for adjuvant systemic therapy in breast cancer (introduced in The Netherlands in 1998) was assessed, as well as the modifications of this guideline, issued in 2001. Both the change in total number of patients eligible for adjuvant therapy, as well as the cost-effectiveness of the changed clinical management of these patients were analysed. PATIENTS AND METHODS: Percentages of patients who would be eligible for adjuvant therapy in 1994, 1998 and 2001 were estimated, based on clinical data from 127 patients, who were operated on in 1994. Ten-year overall survival rates were used as a measure of effectiveness, based on the two most recent EBCTCG meta-analyses. Actual resource costs were calculated. With a decision analytic model, the incremental cost-effectiveness ratios (1998 versus 1994, and 2001 versus 1998) were calculated. RESULTS: The introduction of the 1998 guideline resulted in a relative increase of 80% in the total number of patients eligible for adjuvant therapy, compared with 1994 (from 40% to 72% of all patients with primary breast cancer). With an estimated absolute increase of 10-year overall survival of 2%, the 1998 guideline was found to have an expected incremental cost-effectiveness ratio of about 4837 per life-year gained. CONCLUSIONS: Introduction of the new guideline considerably affected the number of patients eligible for adjuvant systemic therapy for breast cancer. The associated incremental cost-effectiveness ratio is well within the range of values that are generally considered acceptable.

Genetic polymorphisms in UDP-glucuronosyltransferases and glutathione S-transferases and colorectal cancer risk.

Colorectal cancer (CRC) is one of the most common malignancies in the Western world showing an increasing incidence, and has been associated with genetic and lifestyle factors. Individual susceptibility to CRC may be due partly to variations in detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes may result in variations in detoxification activities, which subsequently might influence the levels of toxic/carcinogenic compounds, and this may influence the risk for CRC. To determine whether genetic polymorphisms in detoxification enzymes predispose to the development of CRC, 371 patients with sporadic CRC and 415 healthy controls were genotyped for polymorphisms in the important detoxification enzymes UDP-glucuronosyltransferase UGT1A1, UGT1A6, UGT1A7 and UGT1A8, and glutathione S-transferase GSTA1, GSTM1, GSTP1 and GSTT1. Patients and controls were all of Caucasian origin. DNA was isolated from either blood or tissue and tested by polymerase chain reaction followed by restriction fragment length polymorphism analyses. Logistic regression analyses showed significant age- and gender-adjusted risks for CRC associated with variant genotypes of UGT1A6 [OR 1.5, 95% (confidence interval) CI 1.03-2.3] and UGT1A7 (OR 2.4, 95% CI 1.3-4.6), whereas no associations were found between CRC and the other polymorphic genes as mentioned above. In conclusion, the data suggest that the presence of variant UGT1A6 and UGT1A7 genotypes with expected reduced enzyme activities, might enhance susceptibility to CRC.

Circulating matrix metalloproteinase-9 is transiently elevated after colorectal surgery.

BACKGROUND AND AIMS: Plasma levels of matrix metalloproteinases (MMPs) may yield important information in patients suffering from colorectal cancer but the effect of surgery, a common treatment modality in these patients, on circulating MMP levels is currently unknown. The aim of this study was to assess whether plasma MMP-2 and MMP-9 levels are affected by operative procedures. MATERIALS AND METHODS: In total 128 patients undergoing elective surgery for colorectal cancer (n = 66), liver metastases from colorectal origin (n = 50) and arthrosis of the hip (n = 12) were included in the study. Gelatinase activity was measured, using quantitative gelatin zymography, in plasma obtained before operation and 1 week, 1 month and 3 months postoperatively. RESULTS: One week after operation a significant increase in proMMP-9 activity was measured after colorectal surgery (260%, p = 0.0038), liver surgery (285%, p < 0.0001) and hip surgery (217%, p = 0.012) as compared with preoperative levels. After 1 month proMMP-9 activity had returned to preoperative levels. No effect on proMMP-2 activity was measured. CONCLUSION: Operative procedures have a profound but transient effect on plasma MMP-9 activity. If used to assess disease status, postoperative plasma MMP levels should be interpreted with caution.

Matrix metalloproteinase 2 and 9 activity in patients with colorectal cancer liver metastasis.

BACKGROUND: Matrix metalloproteinases (MMPs) have been reported to play an important role in tumour cell invasion and metastasis. The bioactivity of MMPs in liver metastasis from colorectal cancer was investigated and correlated with clinicopathological variables. METHOD: Thirty-two patients underwent resection of colorectal cancer liver metastases. Latent and active forms of MMP were measured in tissue extracts, by means of quantitative gelatin zymography and a fluorometric activity assay. RESULTS: Broad-spectrum MMP activity, and levels of both active and latent forms of MMP-2 and MMP-9, were higher in tissues containing metastatic tumour than in normal liver tissue. Median metastatic to normal tissue ratios were 15.0 and 17.6 for active and proMMP-2 respectively, and those for active and proMMP-9 were 6.2 and 2.9. The ratios of active to latent enzyme were higher in metastatic tissue than in normal tissue. Lowered MMP-2 activity was associated with large metastatic lesions and increased proMMP-9 levels with preoperative chemotherapy. Both MMP-2 and MMP-9 activity were linked unfavourably to early recurrent disease. CONCLUSION: These data suggest a role for MMPs in colorectal cancer liver metastasis, but indicate different roles for individual MMPs.

Detection of disseminated tumour cells in blood and bone marrow samples of patients undergoing hepatic resection for metastasis of colorectal cancer.

BACKGROUND: In 50-60 per cent of patients who undergo hepatic resection for metastasis of colorectal cancer the first site of tumour recurrence is extrahepatic, indicating the presence of more extensive disease at the time of resection. The aim of this study was to evaluate whether the presence of disseminated tumour cells in blood and bone marrow could predict extrahepatic tumour recurrence. METHODS: Cytokeratin 20 (CK20) reverse transcriptase-polymerase chain reaction was used to study the presence of tumour cells in preoperative peripheral blood and bone marrow samples from 41 patients with liver metastasis scheduled for surgical resection. RESULTS: CK20 expression was detected in six of 41 peripheral blood samples and in eight of 32 bone marrow samples. There was no correlation between CK20-positive samples and subsequent extrahepatic recurrence. Positive blood samples did, however, correlate with high serum carcinoembryonic antigen level and large tumour volume. None of the 14 patients previously treated with chemotherapy had CK20-positive samples, whereas six of 27 blood and eight of 20 bone marrow samples were positive in the chemotherapy-naive group. CONCLUSION: Although the number of patients in this study is limited, the presence of disseminated tumour cells did not predict subsequent extrahepatic recurrence. The results strongly suggest that the presence of circulating tumour cells in peripheral blood may reflect transient shedding of tumour cells related to large tumour volume.

Mitotic activity index in interval breast cancers.

AIMS: The Mitotic Activity Index (MAI) is a strong prognostic factor for disease free survival in breast cancer. The MAI is lower in screen detected tumours, correlating with less aggressive biological behaviour in this group. In this study the MAI is compared between screen detected, interval and symptomatic breast cancers. METHODS: Between 1991 and 1999, the MAI was determined in 581 breast cancers, 160 were detected by screening, 66 were interval carcinomas, and 355 were symptomatic breast cancers. Other prognostic factors were also registered. RESULTS: The interval group had a significantly higher median MAI (17-18, range 1-134) than the screen detected group (7-8, range 0-94,P <0.0001). There was no difference with the symptomatic group (MAI 15, range 0-149,P =0.92). CONCLUSIONS: Interval cancers had an intermediate outcome when correlated with other prognostic factors, compared to screen detected and symptomatic cancers.

Recurrent esophageal fibrovascular polyps: case history and review of the literature.

Fibrovascular esophageal polyps are rare benign tumors. They can grow to considerable length and cause symptoms such as dysphagia, retrosternal discomfort, vomiting, and even asphyxia. A barium contrast esophageal radiography will show a filling defect compatible with an esophageal mass. Surgical removal through cervical esophagotomy is the preferred treatment, and recurrences after surgery are rare. We describe a patient who developed three recurrent giant fibrovascular esophageal polyp within eight years. A review of the literature is given.