Jan Lamote

Catheter tip position as a risk factor for thrombosis associated with the use of subcutaneous infusion ports

AimsThe use of subcutaneous infusion ports has become standard practice to provide a long-term venous access in oncological patients. The aim of this retrospective study was to assess the different complications of infusion ports in our population and to identify predisposing factors.Patients and methodsWe reviewed the medical records of 437 patients who were followed at the Oncology/Haematology Department of our hospital. Of these patients, there were 370 (84.4%) with solid tumours and 58 (13.2%) with haematological disease. The position of the catheter tip was evaluated by reviewing the available chest radiographs or phlebographies.Main resultsAnalysis of the records showed that 346 patients (79.17%) had no complications. The most common complications after implantation were thrombosis (8.46%), catheter dysfunction (4.8%) and infections (4.4%). Univariate and multivariate analysis showed that catheter tip positioning was the most important predisposing risk factor for thrombosis. Catheter tips positioned in the brachiocephalic vein or in the cranial part of the superior vena cava were associated with a high risk of thrombosis. Other significant risk factors were gender and initial diagnosis. Female patients and patients with lung cancer also had an elevated risk of developing a thrombosis.ConclusionsCompared to other reports, we noted a higher rate of thrombosis and port dysfunction. Since catheter tip position was a predisposing factor for developing a thrombosis, correct catheter position has to be ensured during placement. Prophylactic antithrombotic treatment might be beneficial in the event of failure to position the catheter correctly.

Breast imaging. Preoperative breast cancer staging: comparison of USPIO-enhanced MR imaging and 18F-fluorodeoxyglucose (FDC) positron emission tomography (PET) imaging for axillary lymph node staging--initial findings.

Magnetic resonance (MR) imaging after ultra-small super paramagnetic iron oxide (USPIO) injection and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for preoperative axillary lymph node staging in patients with breast cancer were evaluated using histopathologic findings as the reference standard. USPIO-enhanced MR and FDG-PET were performed in ten patients with breast cancer who were scheduled for surgery and axillary node resection. T2-weighted fast spin echo, T1-weighted three-dimensional (3D) gradient echo, T2*-weighted gradient echo and gadolinium-enhanced T1-weighted 3D gradient echo with spectral fat saturation were evaluated. MR imaging before USPIO infusion was not performed. The results were correlated with FDG-PET (acquired with dedicated PET camera, visual analysis) and histological findings. The histopathologic axillary staging was negative for nodal malignancy in five patients and positive in the remaining five patients. There was one false positive finding for USPIO-enhanced MR and one false negative finding for FDG-PET. A sensitivity (true positive rate) of 100%, specificity (true negative rate) of 80%, positive predictive value of 80%, and negative predictive value of 100% were achieved for USPIO-enhanced MR and of 80%, 100%, 100%, 80% for FDG-PET, respectively. The most useful sequences in the detection of invaded lymph nodes were in the decreasing order: gadolinium-enhanced T1-weighted 3D gradient echo with fat saturation, T2*-weighted 2D gradient echo, T1-weighted 3D gradient echo and T2-weighted 2D spin echo. In our study, USPIO-enhanced T1 gradient echo after gadolinium injection and fat saturation emerged as a very useful sequence in the staging of lymph nodes. The combination of USPIO-enhanced MR and FDG-PET achieved 100% sensitivity, specificity, PPV and NPV. If these results are confirmed, the combination of USPIO MR with FDG-PET has the potential to identify the patient candidates for axillary dissection versus sentinel node lymphadenectomy.

Phase I Study of 68Ga-HER2-Nanobody for PET/CT Assessment of HER2 Expression in Breast Carcinoma

Human epidermal growth factor receptor 2 (HER2) status is one of the major tumor characteristics in breast cancer to guide therapy. Anti-HER2 treatment has clear survival advantages in HER2-positive breast carcinoma patients. Heterogeneity in HER2 expression between primary tumor and metastasis has repeatedly been described, resulting in the need to reassess HER2 status during the disease course. To avoid repeated biopsy with potential bias due to tumor heterogeneity, Nanobodies directed against HER2 have been developed as probes for molecular imaging. Nanobodies, which are derived from unique heavy-chain-only antibodies, are the smallest antigen-binding antibody fragments and have ideal characteristics for PET imaging. The primary aims were assessment of safety, biodistribution, and dosimetry. The secondary aim was to investigate tumor-targeting potential. Methods: In total, 20 women with primary or metastatic breast carcinoma (score of 2+ or 3+ on HER2 immunohistochemical assessment) were included. Anti-HER2-Nanobody was labeled with 68Ga via a NOTA derivative. Administered activities were 53–174 MBq (average, 107 MBq). PET/CT scans for dosimetry assessment were obtained at 10, 60, and 90 min after administration. Physical evaluation and blood analysis were performed for safety evaluation. Biodistribution was analyzed for 11 organs using MIM software; dosimetry was assessed using OLINDA/EXM. Tumor-targeting potential was assessed in primary and metastatic lesions. Results: No adverse reactions occurred. A fast blood clearance was observed, with only 10% of injected activity remaining in the blood at 1 h after injection. Uptake was seen mainly in the kidneys, liver, and intestines. The effective dose was 0.043 mSv/MBq, resulting in an average of 4.6 mSv per patient. The critical organ was the urinary bladder wall, with a dose of 0.406 mGy/MBq. In patients with metastatic disease, tracer accumulation well above the background level was demonstrated in most identified sites of disease. Primary lesions were more variable in tracer accumulation. Conclusion: 68Ga-HER2-Nanobody PET/CT is a safe procedure with a radiation dose comparable to other routinely used PET tracers. Its biodistribution is favorable, with the highest uptake in the kidneys, liver, and intestines but very low background levels in all other organs that typically house primary breast carcinoma or tumor metastasis. Tracer accumulation in HER2-positive metastases is high, compared with normal surrounding tissues, and warrants further assessment in a phase II trial.

Tolerance of adjuvant letrozole outside of clinical trials

Recently aromatase inhibitors have become a standard care as an adjuvant treatment for many postmenopausal patients with hormone receptor positive early breast cancer. Adjuvant letrozole was made available either immediately postoperative, after 2-3 years of tamoxifen, or as an extended treatment after 5 years of tamoxifen. Between October 2003 and October 2005, we analyzed the subjective tolerance in 185 postoperative early breast cancer patients receiving letrozole outside of a clinical trial. The most prominent toxicity was musculoskeletal pain. In addition hot flushes, increased fatigue, nausea, vomiting, anorexia, mood disturbances, vaginal dryness, hair loss and rash were also recorded. In contrast to the prospective randomized clinical trials, a high drop-out rate of 20% was documented, mainly due to aromatase inhibitor-associated arthralgia syndrome interfering significantly with the daily life of our patients. Although adjuvant aromatase inhibitors have proven to be generally superior to tamoxifen in the adjuvant setting, it is important to focus attention on the tolerance during the adjuvant therapy and to balance this against the potential benefit in individual patients. Alternative options including switching to tamoxifen remain available.

Comparison of Perindopril and Amlodipine in Cyclosporine-Treated Renal Allograft Recipients

The objective of this study was to compare the antihypertensive efficacy and influence on renal function of perindopril and amlodipine in cyclosporine-treated renal allograft recipients with mild to moderate hypertension. We conducted a randomized, double-blind, double-dummy crossover trial in ambulatory patients. Four phases were conducted: 2 weeks on placebo, 8 weeks of maintenance (perindopril or amlodipine), and 2 weeks of washout between treatment periods. Ten hypertensive patients with stable renal allograft function transplanted more than 6 months previously and receiving cyclosporine as part of their immunosuppressive regimen were studied. The patients were allocated to perindopril (2 or 4 mg/d) and amlodipine (5 mg/d) in a random sequence. If office diastolic pressure was greater than or equal to 90 mm Hg after 4 weeks, the dosage was doubled and continued for another 4 weeks. The main outcome measures were office and 24-hour ambulatory blood pressure changes after 8 weeks of active treatment and treatment and time effect on glomerular filtration rate and effective renal plasma flow. Perindopril and amlodipine were equally effective in lowering office blood pressure and similarly efficacious for the 24-hour period of the day. Neither drug affected glomerular filtration rate or effective renal plasma flow. Both agents demonstrated equivalent capacity (time x treatment, P = .955) to reverse renal vascular resistance (amlodipine from 0.35 +/- 0.02 to 0.30 +/- 0.02 mm Hg/mL per minute per 1.73 m2; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01) (time effect of all treatments together, P = .043).(ABSTRACT TRUNCATED AT 250 WORDS)

Omission of radiotherapy after breast-conserving surgery: survival impact and time trends

PURPOSE To evaluate the survival impact of omission of radiotherapy after breast-conserving surgery and the changes with time. MATERIAL AND METHODS Women aged 40-69 with non-metastasized T1-T2 breast cancer, who underwent breast-conserving surgery with axillary node dissection, with or without post-surgery radiotherapy, selected from the SEER (Surveillance, Epidemiology, and End Results) database. The analysis uses proportional hazards models. RESULTS Omission of radiotherapy as compared to delivery of radiotherapy was associated with an overall increased mortality hazard ratio of 1.346 (95% confidence interval: 1.204-1.504). Test of constancy showed significant changes with time. The time profile suggested an exponential-like increase from a baseline mortality hazard ratio of 1.17, or 17% excess of relative mortality risk, to a projected hazard ratio of 2.26, or more than doubling of relative mortality risk, for omission of radiotherapy. CONCLUSION Omission of radiotherapy in breast-conserving surgery is found to be independently associated with an increase in mortality. The data do not give support to omitting radiation or give rationale to clinical trials that would omit radiation.

Postmastectomy lymphoedema: different patterns of fluid distribution visualised by ultrasound imaging compared with magnetic resonance imaging

OBJECTIVES Postmastectomy lymphoedema remains a disabling complication caused by treatment for breast cancer. The increased thickness of the dermal layer and the increased volume of the subcutis represent the most important contributions to the total swelling of the arm. Ultrasound imaging of the subcutaneous layer results in different patterns of reflected ultrasound waves depending on the morphological alternations that occurred due to impaired lymphatic drainage. The aim of this study was to compare these echographic images with those obtained using magnetic resonance imaging to explain the nature of the morphological changes. DESIGN Observational study. SETTING Patients were recruited from the Breast Clinic at the University Hospital Brussels. PARTICIPANTS Seven women (mean age 60 years) with unilateral breast cancer who subsequently developed lymphoedema. MAIN OUTCOME MEASURES The water displacement technique was applied to determine arm volumes, and echographic and magnetic resonance images were used to evaluate changes in tissue structures. RESULTS Volumetric measurements of the arm (mean affected arm 3241 ml vs unaffected arm 2538 ml) showed a significant increase in total arm volume of 703 ml (95% confidence interval 324 to 1084 ml). Using echography, the thickness of the dermal and subcutaneous layers showed an average increase of 0.2 to 0.8mm and 3.9 to 7.2mm, respectively. The differences between the affected arm and the unaffected arm for all upper and lower arm measurements (i.e. volumetry, dermal and subcutaneous thickness) were significant, but no significant differences were registered for hand measurements. On echography, the dermis showed uniform changes, with a homogenous hypo-echogenic appearance compared with the contralateral side due to water influx. Different patterns of structural changes could be visualised within the subcutis: (1) uniformly hypo-echogenic due to the diffuse spread of water through the subcutis; (2) hyperechogenic areas surrounded by hypo-echogenic streaks visualised on magnetic resonance imaging as adipose tissue surrounded by fluid embedded in fibrous tissue; and (3) homogenously hyperechogenic due to the overgrowth of adipose tissue with a minimal amount of water. CONCLUSIONS Echographic images can help to determine the likelihood that complex physical therapy will reduce lymphoedema, and evaluate treatment results by measuring tissue thickness and evaluating tissue consistency.

Ultrasound elastography as an objective diagnostic measurement tool for lymphoedema of the treated breast in breast cancer patients following breast conserving surgery and radiotherapy

Background. Lymphoedema of the operated and irradiated breast is a common complication following early breast cancer treatment. There is no consensus on objective diagnostic criteria and standard measurement tools. This study investigates the use of ultrasound elastography as an objective quantitative measurement tool for the diagnosis of parenchymal breast oedema. Patients and methods. The elasticity ratio of the subcutis, measured with ultrasound elastography, was compared with high-frequency ultrasound parameters and subjective symptoms in twenty patients, bilaterally, prior to and following breast conserving surgery and breast irradiation. Results. Elasticity ratio of the subcutis of the operated breast following radiation therapy increased in 88.9% of patients, was significantly higher than prior to surgery, unlike the non operated breast and significantly higher than the non operated breast, unlike preoperative results. These results were significantly correlated with visibility of the echogenic line, measured with high-frequency ultrasound. Big preoperative bra cup size was a significant risk factor for the development of breast oedema. Conclusions. Ultrasound elastography is an objective quantitative measurement tool for the diagnosis of parenchymal breast oedema, in combination with other objective diagnostic criteria. Further research with longer follow-up and more patients is necessary to confirm our findings.

Divergent effects of calcium channel and angiotensin converting enzyme blockade on glomerulotubular function in cyclosporine-treated renal allograft recipients

The effects of amlodipine and perindopril on renal hemodynamics and tubular function in cyclosporine-treated hypertensive renal allograft recipients were evaluated in a randomized, double-blind crossover fashion. Ten patients were studied after a 2-week placebo run-in and, after 8 weeks of active treatment, allowing a 2-week placebo washout between treatments. At the end of each period, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured as 51Cr-EDTA and 123I-hippuran clearance, respectively, and tubular function evaluated by the lithium clearance technique was determined. Both drugs maintained GFR and ERPF and lowered mean arterial pressure (MAP, mm Hg) to a similar extent (time x treatment, P = 0.466): amlodipine from 126.9 +/- 2.5 to 115.9 +/- 2.2; perindopril from 126.9 +/- 2.5 to 117.9 +/- 3.9 (time effect of all treatments together, P = 0.003). Accordingly, renal vascular resistance (RVR, mm Hg/mL/min/1.73 m2) was equally reduced (time x treatment, P = 0.955): amlodipine from 0.36 +/- 0.03 to 0.30 +/- 0.02; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01 (time effect all treatments together, P = 0.043). Sodium clearance and fractional excretion of sodium were not affected by either drug. Output of fluid from the proximal tubules measured as clearance of lithium (CLi, mL/min) and uric acid (CUr, mL/min) was higher after amlodipine than after perindopril (CLi 19.1 +/- 2.1 v 16.5 +/- 1.7, P =0.036 and CUr 7.0 +/- 0.6 v 5.9 +/- 0.4, P = 0.007). As a consequence, after amlodipine, distal absolute reabsorption of sodium was higher (DARNa 2.57 +/- 0.28 v 2.19 +/- 0.22 mEq/min, P = 0.027) and serum uric acid was lower (5.9 +/- 0.3 v 6.7 +/- 0.4 mg/dL, P = 0.001) in comparison with perindopril. In cyclosporine-treated renal allograft hypertensives, amlodipine and perindopril lower blood pressure equally and reduce RVR to the same extent. Overall sodium excretion is not affected by either agent. Urate clearance is higher and serum uric acid lower on amlodipine as compared with perindopril.

Survival benefit with radiation therapy in node-positive breast carcinoma patients.

Background and Purpose:Postoperative radiation therapy (RT) has been the subject of discussion, especially in patients with one to three positive lymph nodes (≤ 3 pN+) in the axillary dissection. The authors investigated whether postoperative RT provides a survival benefit for pT1–2 pN+ breast cancer patients.Patients and Methods:Patients included were selected from the SEER database (NCI – Surveillance, Epidemiology and End Results, release 2000; n = 24,410) and the UZ Brussel database (1984–2002; n = 1,011) according to the following criteria: women aged 25–95, no previous cancer, unilateral pT1–pT2 breast tumors, total mastectomy (ME) or breast-conserving surgery (BCS), postoperative RT, and an axillary dissection showing at least one pathologic lymph node.Results:The overall survival (OS) of patients in the SEER and UZ Brussel databases who received postoperative RT was identical. However, patients in the SEER database who did not receive RT had a significantly worse outcome (p < 0.0001). After ME or BCS, all patients (SEER and UZ Brussel) who had ≥ 4 pN+ and received RT had comparable outcomes after 15 years. The 15-year OS in the subgroup with ME and ≤ 3 pN+ nodes was 57.0% and 46.6% (p = 0.0004) with RT (UZ Brussel) and without RT (SEER), respectively. For BCS and ≤ 3 pN+, the same significant difference in OS at 15 years was seen: 63.8% after RT (UZ Brussel) and 60.4% without RT (SEER; p = 0.0029).Conclusion:RT provides a survival benefit in patients with ≤ 3 or ≥ 4 pN+; the indication for postoperative RT should therefore be adapted in future consensus meetings.Hintergrund und Ziel:Der Nutzen einer postoperativen Strahlentherapie (RT) wird diskutiert, insbesondere bei Patientinnen mit einem bis drei befallenen Lymphknoten (≤ 3 pN+). In der vorliegenden Studie wird untersucht, ob die postoperative RT fur Patientinnen mit Mammakarzinom im Stadium pT1–2 pN+ einen Überlebensvorteil bietet.Patienten und Methodik:Die Patientinnen wurden aus der SEER-Datenbank (NCI – Surveillance, Epidemiology and End Results, Ausgabe 2000; n = 24 410) und der Datenbank des UZ Brussel (1984–2002; n = 1 011) ausgewahlt. Berücksichtigt wurden folgende Kriterien: Frauen im Alter von 25–95 Jahren, keine Krebserkrankung in der Vorgeschichte, unilaterale Mammakarzinome Stadium pT1–pT2, Mastektomie (ME) oder brusterhaltende Operation (BCS [„breast-conserving surgery“]), postoperative RT und Axilladissektion mit mindestens einem befallenen Lymphknoten.Ergebnisse:Das Gesamtüberleben (OS [„overall survival“]) der Patientinnen aus der SEER-Datenbank und der Datenbank des UZ Brussel, die postoperativ bestrahlt worden waren, war identisch. Demgegenüber fand sich bei Patientinnen aus der SEER-Datenbank, die keine postoperative RT erhalten hatten, ein schlechteres Ergebnis (p < 0,0001). Unabhangig von der Art des operativen Eingriffs (ME oder BCS) zeigten alle Patientinnen (SEER und UZ Brussel), die ≥ 4 pN+ aufwiesen und eine RT erhalten hatten, vergleichbare Resultate nach 15 Jahren. Das 15-Jahres-OS in der Untergruppe mit ME und ≤ 3 pN+ betrug 57,0% und 46,6% (p = 0,0004) mit RT (UZ Brussel) bzw. ohne RT (SEER). Bei Patientinnen nach BCS und ≤ 3 pN+ zeigte sich der gleiche signifikante Unterschied im OS nach 15 Jahren: 63,8% nach RT (UZ Brussel) und 60,4% ohne RT (SEER; p = 0,0029).Schlussfolgerung:Die RT bietet sowohl fur Patientinnen mit ≤ 3 als auch mit ≥ 4 pN+ einen Uberlebensvorteil; deshalb sollte in künftigen Konsensuskonferenzen die Indikationsstellung für eine postoperative RT angepasst werden.