Intraoperative ultrasound guidance for excision of non-palpable invasive breast cancer: a hospital-based series and an overview of the literature.

Intraoperative ultrasound (IOUS) can be used in the operation theatre for localization of non-palpable breast cancers. In this prospective cohort study, we compared the yield of IOUS to guidewire localization (GWL). A total of 258 consecutive patients with non-palpable invasive breast cancer underwent breast conserving surgery between 1999 and 2010. GWL was performed in 138 (54 %) and IOUS in 120 (46 %) patients. Tumor dimensions, resection volume, margin status and re-excision rates were compared by means of multivariate regression analysis. The groups were similar in terms of age, histological subtype and presence of DCIS. Lesions in the IOUS group were larger (1.24 vs. 0.98 cm, P < 0.001), while microcalcifications were more common in the GWL group (19 vs. 3 %, P < 0.001). Even after stratification for tumor diameter, presence of DCIS and findings on mammography, resection volumes were similar in both groups. Tumor-free resection margins were obtained in >93 % of patients (93.5 % with GWL vs. 93.3 % with IOUS, P = 0.958) and re-excision was performed in 11 % of patients undergoing GWL and 12.5 % of patients undergoing IOUS (P = 0.684). For localization of non-palpable breast cancer, IOUS is a reliable alternative to GWL, as it achieves similar results in terms of complete tumor removal, re-excision rate and excised volume.

Prognostic value of micrometastases in sentinel lymph nodes of patients with breast carcinoma: a cohort study.

BACKGROUND: The prognostic meaning and thus indication for adjuvant therapy of lymphogenic micrometastases in breast cancer patients is still under debate. PATIENTS AND METHODS: From 1999 to 2007, 703 patients with (c)T(1-2)N(0) breast cancer underwent surgery including sentinel lymph node biopsy. Examination of sentinel lymph nodes consisted of hematoxylin and eosin and immunohistochemistry staining following serial sectioning of the sentinel node. Patients were divided into four groups: (p)N(0) (n=423), (p)N(1micro) (n=81), (p)N(1a) (n=130) and (p)N(>or=1b) (n=69). Median follow-up was 40 months. RESULTS: At the end of follow-up, 53 patients had died and 64 had recurrent disease. Compared with (p)N(0) and following adjustment for possible confounders, including adjuvant systemic treatment, overall survival was not significantly different for (p)N(1micro) while significantly worse for (p)N(1a) and (p)N(>or=1b) {hazard ratio (HR) [95% confidence interval (CI)]: 0.59 [0.14-2.58], 4.31 [1.85-10.01], 10.66 [4.04-28.14], respectively}. Likewise, disease-free survival was not significantly different for (p)N(1micro) and worse for (p)N(1a) and (p)N(>or=1b) (HR [95% CI]: 1.43 [0.67-3.02], 2.79 [1.37-5.66], 7.13 [3.27-15.54], respectively). Distant metastases were more commonly observed in the (p)N(1micro) than in the (p)N(0) group, but still not as common as in the (p)N(1a) or (p)N(>or=1b) group (HR [95% CI]: 4.85 [1.79-13.18], 10.34 [3.82-28.00], 23.25 [7.88-68.56], respectively). CONCLUSION: Although the risk of distant metastases was higher in patients in the (p)N(1micro) than in the (p)N(0) group, no statistically significant differences were observed in overall or disease-free survival between (p)N(0) and (p)N(1micro). Micrometastatic lymph node involvement in itself should not be an indication for adjuvant chemotherapy in breast cancer patients.

Introduction of sentinel node biopsy and stage migration of breast cancer.

AIM: The purpose of this study was to examine in a large population based group of breast cancer patients treated in a regular care setting whether the introduction of the Sentinel Node Biopsy (SNB) led to detection of a higher percentage of patients with positive regional lymph nodes. METHODS: The study includes 3665 early breast cancer patients, aged 30-85 years, diagnosed in the period 1997-2002 and registered at the Regional Cancer Registry of the Comprehensive Cancer Centre Middle Netherlands. During this period the SNB was introduced. The outcome of staging was compared for groups staged with or without SNB. A logistic regression model was used to adjust for age, calendar period and tumour size. RESULTS: Overall a quarter of all patients over the period 1997-2002 underwent a SNB as method of lymphatic staging. The use of SNB clearly increased over time: from 2% in 1998 to 65% in 2002. The percentage node positive patients also rose significantly; before introduction of the SNB 30% of all patients were diagnosed with positive lymph nodes, and after SNB introduction this percentage was 40%. The increase is largely explained by the increase of patients diagnosed with only micrometastases. Adjustment did not change the results. CONCLUSION: In conclusion, introduction of the SNB in early breast cancer led to significant upstaging of breast cancer patients treated in a regular care setting, due to the detection of more micrometastases. Since the relevance of micrometastases for long term survival is not yet known, this upstaging potentially led to over treatment of patients. On the other side, for some patients axillary lymph node dissection was prevented by the SNB procedure, preventing comorbidity.

Effects of benfluorex on insulin resistance and lipid metabolism in obese type II diabetic patients.

OBJECTIVE: To evaluate the change in lipids and insulin sensitivity in 10 obese type II diabetic patients after treatment with benfluorex or placebo for 2 wk. RESEARCH DESIGN AND METHODS: The study had a double-blind, cross-over design. Insulin sensitivity was measured with the euglycemic hyperinsulinemic glucose clamp technique at two different insulin infusion rates: 0.05 (clamp 1) and 0.10 U.kg-1.h-1 (clamp 2). RESULTS: Subanalysis of the glucose infusion rate under steady-state conditions in the last 30 min of clamp 2 yielded a glucose infusion rate of 5.36 and 3.87 mmol.kg-1.min-1 after benfluorex and placebo, respectively (P = 0.018). CONCLUSIONS: Benfluorex increases insulin sensitivity in obese type II diabetic patients.

The relation between cancer incidence among relatives and the occurrence of multiple primary carcinomas following head and neck cancer.

Despite improvement in therapeutic modalities in head and neck squamous cell carcinoma (HNSCC) the overall survival rate has only marginally improved during the last decades. The occurrence of second primary tumors (SPTs) in the respiratory and upper digestive tract (RUDT) is the main cause of treatment failure in early stage HNSCC. Identification of risk factors for the development of SPT by epidemiological analysis may lead to better risk assessment in individual cases. Ninety-seven HNSCC patients who ultimately developed SPTs and 100 HNSCC patients who remained free of other carcinomas after treatment of the first for a minimal period of 6 years were interviewed about the incidence of RUDT carcinomas within parents and siblings. All questioned patients were smokers. Among the SPT-positive patients, 50 (8.9%) of the 562 family members were reported to have had cancer of the respiratory or upper digestive tract versus 16 (2.5%) of the 629 family members of the SPT-negative patients. This difference was statistically significant (P < 0.0001) with the stratified version of Fisher's exact test. All these 66 probands with RUDT cancer were smokers, and the percentages of smokers were similar in both proband groups. Neither age and sex of the patient, nor tumor stage influenced the occurrence of SPTs in this study. The percentages of probands with tumors outside the RUDTs were almost similar, 8.0 and 7.0% in the SPT-positive and -negative groups, respectively. Having one or more relatives with RUDT cancer was established as a risk factor (odds ratio, 3.8; 95% confidence interval, 2.0-7.6) for patients with initial HNSCC to develop an SPT. These findings suggest that, in addition to external carcinogens, an intrinsic susceptibility may influence the risk for the development of SPTs in HNSCC patients.

Lack of effect of daily N-acetylcysteine supplementation on mutagen sensitivity.

The European Organization for Research and Treatment of Cancer multicenter Euroscan trial was set up to prevent the occurrence of second primary tumors in the upper aerodigestive and respiratory tract in patients cured for early stage head and neck squamous cell carcinoma. One randomized group of patients receive daily N-acetylcysteine, an antioxidant that may be protective especially in the early steps of carcinogenesis. Mutagen sensitivity, measured as sensitivity to bleomycin in peripheral blood lymphocytes, has been found to be increased in head and neck squamous cell carcinoma and is hypothesized to reflect cancer susceptibility. The aim of this study was to investigate whether mutagen sensitivity is influenced by oral N-acetylcysteine supplementation and can therefore be used as intermediate end point in chemoprevention. Patients (n = 19) who had various periods of N-acetylcysteine supplementation (600 mg daily for 3-9 months) were analyzed. In addition, a patient group (n = 14) that did not receive N-acetylcysteine supplementation was analyzed for comparison. Our results show no evidence that administration of N-acetylcysteine did influence the mutagen sensitivity level. The only explanatory variable in the analysis of the difference between two samples of one person was the b/c value of the first measurement. Moreover, the variability in these repeated measurements (coefficient of variation of 14%) indicates that additional studies should be performed to minimize this variability and to optimize the testing of mutagen sensitivity to accurately identify individual patients at high risk for the development of multiple primary tumors.

Antioxidant-related parameters in patients treated for cancer chemoprevention with N-acetylcysteine.

N-acetylcysteine (NAC) is an antioxidant, possibly effective in the early steps of carcinogenesis, and is applied to prevent second primary tumours in the upper aerodigestive tract and the lungs. In this study, we evaluated the pharmacodynamic profile of 600 mg NAC treatment, given daily for 3 months. Treatment caused a significant increase of the non-protein-SH concentration in blood plasma (38%) and erythrocytes (31%). Glutathione levels in exfoliated buccal mucosa cells appeared not to be influenced by treatment. The total radical-trapping ability parameter (TRAP) of blood plasma showed no change. In vitro, the addition of glutathione, but not of NAC did increase the TRAP value. In addition, when peroxyl radicals were generated in vitro, NAC was shown to be consumed more rapidly than glutathione. This suggests that NAC prevents early damage, while glutathione functions over a longer time period.

The influence of common variables on T cell subset analysis by monoclonal antibodies.

Normal values for T cell subsets as defined by the most commonly used monoclonal antibodies of the OKT series were determined in a group of 142 unrelated normal individuals. In most age classes females had significantly greater portions of OKT3 and OKT4 antigen bearing lymphocytes and accordingly a higher T4/T8 index. The range of individual normal values within the control population was remarkably wide. Intra-individual differences between the T subset composition remained rather constant over a period of 2 months. Time of day, food absorption and physical exercise had no influence on the results of subset analyses. Storage of the blood sample and freezing of isolated lymphocytes can result in significantly reduced OKT3 and OKT4 positive cell numbers. If lymphocytes were isolated soon after the blood was taken and resuspended in a stabilization medium they exhibited only minimal change.

Acute liver necrosis induced by iodine-131-MIBG in the treatment of metastatic carcinoid tumors.

Iodine-131-metaiodobenzylguanidine (MIBG) is used in the treatment of carcinoid tumors. Temporary palliation with complete subjective symptomatic response has been reported in these patients. This treatment is usually well tolerated and side-effects are generally limited to nausea, mild hepatic toxicity with spontaneous recovery and temporary myelosuppression. Our case report shows that repeated treatment with [131I]MIBG in a patient with extensive carcinoid liver metastasis may cause severe hepatic toxicity leading to death. Factors such as concomitant use of 5-fluorouracil and the progressive nature of the disease may have contributed to this event.

Detection of malignant breast tumours in dense breast tissue: results of 99mTc-tetrofosmin scintimammography related to surgery.

AIMS: To assess the contribution of 99mTechnetium tetrofosmin (99mTc-TF) scintimammography for staging of breast lesions in patients with a suspicious or non-diagnostic mammogram to reduce unnecessary surgical procedures in future. METHODS: Fifty patients with suspicious physical examinations and/or mammography underwent 99mTc-TF breast imaging. RESULTS: Scintimammography with 99mTc-TF was positive in 37 patients (36 true positive, one false positive) and negative in 13 patients (12 true negative, one false negative). The detection of a malignant tumour by 99mTc-TF was independent of the density of the breast tissue. In 33 patients with a malignant breast tumour 99mTc-TF was diagnostic with respect to axillary status, but in four out of 19 patients with a histologically positive axillary lymph node status, tumour involvement remained undetected by scintigraphy. Moreover, in four patients, scintimammography revealed an additional discrete area of increased 99mTc-TF uptake, which proved to be second primary breast cancers. CONCLUSIONS: 99mTc-TF scintimammography appears to be an accurate diagnostic test in patients with a symptomatic breast lesion and a non-diagnostic mammogram, also in those patients with dense breast tissue. This procedure may also have potential for the detection of second primary breast cancers in an early stage.

Serum proteinase activities in head and neck squamous cell carcinoma patients.

Proteinases are known to be involved in carcinogenesis, and various substrates are now available to measure the activity of these enzymes. No suitable serum tumour marker for head and neck squamous cell carcinoma (HNSCC) exists at this moment. Therefore, we compared proteinase-activity in serum of 20 untreated HNSCC patients with that of 20 non-cancer individuals. When N-benzoyl-DL-arginine-beta-naphtylamide (BANA) was used as the substrate, proteinase-activity seemed higher among patients, but this difference disappeared after adjustment for alcohol and tobacco consumption. Applying N-a-benzoyloxycarbonyl-L-arginyl-L-arginine-7-amido-4-methylcou marine (ZAAM) as the substrate no difference was found. Addition of E-64, an inhibitor of cysteine proteinase showed that cathepsin B contributed minimally to the ZAAM-specific activity.

Primary oligoarthritis in a parent of a child with meningococcal group B sepsis and meningitis.

The mother of an eight-month-old child with meningitis presented with petechiae on her trunk and lower extremities, fever, and oligoarthritis. Although pathogens were never revealed by Gram stain nor cultured from the aspirated joint fluid, the diagnosis was primary meningococcal arthritis. This diagnosis was based on the simultaneous occurrence of Neisseria meningitidis group B infection in her son and the clinical presentation.

The value of renal scintigraphy in the conservative management of a patient with tuberous sclerosis.

The diagnostic dilemma to differentiate angiomyolipomas from renal cell carcinoma has been resolved by computerized tomography and sonography. However, these imaging modalities are incapable of estimating the functional contribution of individual kidneys. Renal scintigraphy can be used for a quantitative impression of renal function and is, therefore, of additional value in monitoring conservatively treated tuberous sclerosis patients as shown by the case report.

FDG positron emission tomography in head and neck cancer: pitfall or pathology?

PURPOSE: Fluorodeoxyglucose (FDG) positron emission tomography (PET) is a functional imaging technique used for imaging and staging malignant diseases. In many oncologic situations, however, abnormal changes seen on the PET studies are not caused by tumor, which is especially true in the head and neck region. The authors present an overview of the phenomena that may confound the interpretation of the images in head and neck cancer. MATERIALS AND METHODS: FDG PET studies were performed in patients with primary head and neck cancer and in patients in whom recurrent disease was likely. The results were correlated with clinical findings. Eight solitary cases were selected from a total of 180 patients studied. RESULTS AND CONCLUSIONS: Benign lesions and iatrogenic and physiologic changes may show increased FDG uptake. Therefore, clinical information on previous surgical interventions and optimal patient preparation are necessary for adequate interpretation. If these prerequisites can be met, benign lesions appear to be the only lesions that may interfere with the specificity of FDG PET.

The impact on post-surgical treatment of sentinel lymph node biopsy of internal mammary lymph nodes in patients with breast cancer.

BACKGROUND: Since the introduction of the sentinel lymph node (SLN) biopsy in breast cancer patients there is a renewed interest in lymphatic drainage to the internal mammary (IM) chain nodes. We evaluated the frequency of lymphatic drainage to the IM chain, the rate of SLNs that contain metastases and the clinical implications of IM LN metastases. METHODS: Between June 1999 and April 2005 506 consecutive patients underwent SLN biopsy as a staging procedure for clinically T1-2N0 breast cancer. In all patients preoperative lymphoscintigraphy was combined with the intraoperative use of a gammaprobe. In patients with IM SLNs visualized on lymphoscintigraphy, LNs were extirpated through an intercostal parasternal incision. RESULTS: SLNs were visualized by preoperative lymphoscintigraphy in 99% of all patients (502/506): axillary SLNs in 499 patients (99%), ipsilateral IM LNs in 109 patients (22%). In 85 patients with visualized IM SLNs the IM nodes could be removed (78%). In 20 of the latter 85 patients IM SLNs contained metastases (24%). IM metastases were associated with axillary LN metastases (P < 0.001). In 17 patients IM metastases led to extension of the radiotherapy field, while additional (adjuvant) systemic therapy was given in six patients. CONCLUSION: SLNs in the IM chain are common in breast cancer patients and can be extirpated in the majority of these patients. The proportion of patients in whom radiotherapeutic treatment was adjusted due to IM LN metastases was substantial. We advocate retrieval of IM SLNs when visualized by preoperative lymphoscintigraphy.