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.

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.

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.

F-18-fluoro-deoxy-glucose positron-emission tomography scanning in detection of local recurrence after radiotherapy for laryngeal/ pharyngeal cancer.

BACKGROUND: The objective of this investigation was to determine whether F18-fluoro-deoxy-glucose (FDG) positron-emission tomography (PET) could differentiate between local recurrence and late radiation effects after radiotherapy for laryngeal/pharyngeal cancer. METHODS: In a prospective study of 75 patients (67 larynx, eight oro/hypopharynx), 160 laryngoscopies and 109 FDG PET scans were performed on the head and neck region. The mean follow-up time after the first FDG PET scan was 23 months (minimum 1 year). RESULTS: Local recurrence was diagnosed in 37 patients: 19 after the first biopsy and 18 after follow-up biopsies. For all of the negative initial FDG scans (27), the biopsies that were taken at the same time were negative and no recurrence was seen for at least 1 year. The first FDG scan was a true positive in 34 of 48 patients. In 12 of the 14 patients with false-positive results, FDG scans were repeated; a decreased FDG uptake was found in 9 of the 12. The sensitivity and specificity of the first scan were respectively 92% and 63%; including subsequent FDG scans, the rates were 97% and 82%, respectively. CONCLUSIONS: When a local recurrence is suspected after radiotherapy for cancer of the larynx/pharynx, an FDG PET scan should be the first diagnostic step. No biopsy is needed if the scan is negative. If the scan is positive and the biopsy negative, a decreased FDG uptake measured in a follow-up scan indicates that a local recurrence is unlikely.

Assessment of renal artery stenosis: comparison of captopril renography and gadolinium-enhanced breath-hold MR angiography.

AIM: To determine the accuracy of captopril renography (CR) and gadolinium-enhanced breath-hold magnetic resonance (MR) angiography in the diagnosis of 50-99% renal artery stenosis (RAS). MATERIALS AND METHODS: Forty-three patients with possible RAS, of whom 53% had renal function impairment (creatinine >130 micromol/l), were included.(99m)Tc-mercaptoacetyl triglycine (MAG(3)) renography was performed after an oral dose of 25 mg captopril. Gadolinium-enhanced MR angiography was performed on a standard 1.5 Tesla system: TR 13.5, TE 3.5, flip angle 60 degrees, matrix 195 x 512. Intra-arterial digital subtraction angiography (DSA) was the standard of reference. RESULTS: Captropril renography accurately categorized 22 of 26 patients who had either uni- or bilateral RAS of 50-99%. The sensitivity and specificity of CR for the detection of 50-99% stenosis were 85 and 71%, respectively. With MR angiography one occluded artery was incorrectly diagnosed as a stenosis. Sensitivity and specificity were 100 and 94%, respectively. The difference between the accuracies of MR angiography and CR was statistically significant (P = 0.02). The accuracy of CR was lower in patients with renal impairment (70%) than in those with normal renal function (90%). CONCLUSION: MR angiography showed a high accuracy in diagnosing RAS of between 50 and 99%. CR was less accurate than MR angiography, especially in patients with renal function impairment. In patients with normal renal function, however, CR remains a useful diagnostic test.

Interferon-alpha induced changes in CEA expression in patients with CEA-producing tumours.

Enhancement of antigen expression could result in improved tumour targeting using antibodies directed to the antigen. In this study we performed radioimmunoscintigraphy using 99mTc-CEA-Scan to analyse the effect of interferon-alpha (IFN-alpha) in enhancing the expression of carcinoembryonic antigen (CEA) in ten patients with CEA-producing tumours. Furthermore, we investigated the feasibility of a future therapeutic study with this antibody fragment labelled with rhenium-186. Although IFN-alpha gave rise to a significant increase in antibody uptake by the tumour, the absolute antibody uptake in the tumour appeared to be poor, with a mean of 0.475% of injected dose (ID) in the tumour before IFN-alpha, rising to 0.562% ID in the tumour after IFN-alpha. Pharmacokinetic analysis demonstrated no significant alterations after IFN-alpha. In conclusion, the administration of IFN-alpha is an attractive way to achieve enhanced tumour targeting, although the increase was of little clinical significance in this patient population and using this antibody fragment.

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.

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.

Towards quality assurance of the sentinel node procedure in malignant melanoma patients: a single institution evaluation and a European survey.

The status of the regional lymph node (LN) is a critical component in staging patients with malignant melanoma. Biopsy of the first tumour-draining LN (sentinel node, SN) may replace routine elective LN dissection. However, until now, the applied methods have differed widely. Therefore, the aim of this study was to formulate recommendations for the pre-operative identification and intra-operative retrieval of the SN. We present the results of an independent survey of the clinical practice of the SN procedure via a postal questionnaire among 136 nuclear physicians in different institutes throughout 16 European countries. Moreover, the results of the SN procedure in our institution in an open prospective intervention trial in 80 patients with malignant melanoma without palpable LNs are also presented. In our protocol, on average, 6 h prior to surgery, 80 MBq technetium-99m nanocolloid was injected intracutaneously around the circumference of the diagnostic excision scar of the primary melanoma. No additional blue dye procedure was used to judge the accuracy of the radioguided SN procedure on its own. For successful identification of the radiolabelled SN, dynamic and static images were performed and the skin projection of the detected SN was marked with a cobalt-57 source. For intra-operative mapping a hand-held gamma probe was used. Forty of the 83 respondents of the European-wide questionnaire (48%) performed the SN procedure. Although many different regimens are used, the following recommendations could be deduced for the SN procedure in patients with malignant melanoma and non-palpable LNs: (1) local, intradermal injection of 40 MBq 99mTc-nanocolloid around the diagnostic excision scar of the primary melanoma; (2) two-phase LS: dynamic imaging (20 frames of 60 s, 128x128 matrix, LEAP collimator) followed by static images 1-2 h later (180 s per record); (3) intra-operative retrieval of the SN with a gamma probe; (4) histopathological examination of the SN on serial sections. In our trial, surgical retrieval of the SN was successful in 95% of the cases. Dynamic lymphoscintigraphy (LS) contributed to the SN procedure by showing anatomically unpredictable lymph flow to extra-regional SNs (10% of the patients in this study) and multiple SNs. Of the 77 retrieved SNs, 13 contained metastatic disease (17%). Consequently, these patients underwent a formal LN dissection of the affected basin. In conclusion, the SN concept is a rational approach to select patients who could, theoretically, benefit from early LN dissection of the affected basin. Standardisation of the SN procedure will improve the results of this approach, and could be useful for quality control and for making comparisons with other countries in coming years.

[Full working capacity instead of threatened retirement. Thrombendarterectomy in chronic thromboembolic pulmonary hypertension]. / Volle Arbeitsfähigkeit statt drohender Berentung. Thrombendarterektomie bei chronischer thromboembolischer pulmonaler Hypertonie.

HISTORY AND CLINICAL FINDINGS: A 56-year-old man in marked right heart failure (stage III-IV of the New York Heart Association classification) and severe pulmonary hypertension was admitted to a rehabilitation clinic for therapeutic and social-medical assessment. On physical examination the important features were markedly distended neck veins, tachycardia at rest (90/min), a loud 2nd pulmonary sound and dyspnea. INVESTIGATIONS AND DIAGNOSIS: Non-invasive tests (ECG, echocardiography, abdominal ultrasound and lung functions) confirmed right heart failure; invasively obtained haemodynamic data indicated its severity. Selective pulmonary angiography defined the embolisation to be central and bilateral. TREATMENT AND COURSE: As intensive drug treatment and physiotherapy had failed to achieve significant improvement, operative removal of the bilateral central and some segmental pulmonary thrombi was performed and an inferior vena caval filter inserted. Immediately after operation the markedly elevated right-heart and pulmonary artery pressures fell markedly and there was dramatic improvement in the patient's general condition and in his physical capacity. Angiography demonstrated largely normal pulmonary perfusion. Instead of the anticipated retirement, the patient was discharged on anticoagulants, in the expectation of a return to full-time work. CONCLUSION: With pulmonary thrombendarterectomy severe chronic thromboembolic pulmonary hypertension may well be treated.

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.

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.

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.

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.