Axillary staging for breast cancer during pregnancy: feasibility and safety of sentinel lymph node biopsy.

BACKGROUND: Safety of sentinel lymph node (SLN) biopsy for breast cancer during pregnancy is insufficiently explored. We investigated efficacy and local recurrence rate in a large series of pregnant patients. PATIENTS AND METHODS: Women diagnosed with breast cancer who underwent SLN biopsy during pregnancy were identified from the International Network on Cancer, Infertility and Pregnancy, the German Breast Group, and the Cancer and Pregnancy Registry. Chart review was performed to record technique and outcome of SLN biopsy, locoregional and distant recurrence, and survival. RESULTS: We identified 145 women with clinically N0 disease who underwent SLN during pregnancy. The SLN detection techniques were as follows: 99mTc-labeled albumin nanocolloid only (n = 96; 66.2%), blue dye only (n = 14; 9.7%), combined technique (n = 15; 10.3%), or unknown (n = 20; 13.8%). Mapping was unsuccessful in one patient (0.7%) and she underwent an axillary lymph node dissection (ALND). Mean number of SLNs was 3.2 (interquartile range 1-3; missing n = 15). Positive SLNs were found in 43 (29.7%) patients and 34 subsequently underwent ALND. After a median follow-up of 48 months (range 1-177), 123 (84.8%) patients were alive and free of disease. Eleven patients experienced a locoregional relapse, including 1 isolated ipsilateral axillary recurrence (0.7%). Eleven (7.6%) patients developed distant metastases, of whom 9 (6.2%) died of breast cancer. No neonatal adverse events related to SLN procedure during pregnancy were reported. CONCLUSIONS: SLN biopsy during pregnancy has a comparably low axillary recurrence rate as in nonpregnant women. Therefore, this method can be considered during pregnancy instead of standard ALND for early-stage, clinically node-negative breast cancer.

Dosimetric parameters predicting contralateral liver hypertrophy after unilobar radioembolization of hepatocellular carcinoma.

PURPOSE: This study aimed at identifying prior therapy dosimetric parameters using 99mTc-labeled macro-aggregates of albumin (MAA) that are associated with contralateral hepatic hypertrophy occurring after unilobar radioembolization of hepatocellular carcinoma (HCC) performed with 90Y-loaded glass microspheres. METHODS: The dosimetry data of 73 HCC patients were collected prior to the treatment with 90Y-loaded microspheres for unilateral disease. The injected liver dose (ILD), the tumor dose (TD) and healthy injected liver dose (HILD) were calculated based on MAA quantification. Following treatment, the maximal hypertrophy (MHT) of an untreated lobe was calculated. RESULTS: Mean MHT was 35.4 ± 40.4%. When using continuous variables, the MHT was not correlated with any tested variable, i.e., injected activity, ILD, HILD or TD except with a percentage of future remnant liver (FRL) following the 90Y-microspheres injection  (r = -0.56). MHT ≥ 10% was significantly more frequent for patients with HILD ≥ 88 Gy, (52% of the cases), i.e., in 92.2% versus 65.7% for HILD < 88 Gy (p = 0.032). MHT ≥ 10% was also significantly more frequent for patients with a TD ≥ 205 Gy and a tumor volume (VT) ≥ 100 cm3 in patients with initial FRL < 50%. MHT ≥10% was seen in 83.9% for patients with either an HILD ≥ 88 Gy or a TD ≥ 205 Gy for tumors larger than 100cm3 (85% of the cases), versus only 54.5% (p = 0.0265) for patients with none of those parameters. MHT ≥10% was also associated with FRL and the Child-Pugh score. Using multivariate analysis, the Child-Pugh score (p < 0.0001), FRL (p = 0.0023) and HILD (p = 0.0029) were still significantly associated with MHT ≥10%. CONCLUSION: This study demonstrates for the first time that HILD is significantly associated with liver hypertrophy. There is also an impact of high tumor doses in large lesions in one subgroup of patients. Larger prospective studies evaluating the MAA dosimetric parameters have to be conducted to confirm these promising results.

10-Year experience regarding the reliability and morbidity of radio guided lymph node biopsy in penile cancer patients and the associated radiation exposure of medical staff in this procedure.

BACKGROUND: The guidelines of the European Association of Urologists (EAU), of the German Society of Nuclear Medicine (DGN), and the European Society for Medical Oncology (ESMO) recommend sentinel lymph node biopsy (SLNB) for lymph node staging in penile cancer with non-palpable inguinal lymph nodes as one diagnostic method. Despite this, the method is neither widely nor regularly applied in Germany - the same applies to many other countries, which may be due to insecurity in dealing with open radioactive tracers. This study aims to assess the reliability and morbidity of this method, as well as the associated radioactive burden for clinical staff. METHODS: Between 2006 and 2016, 34 patients with an invasive penile carcinoma and inconspicuous inguinal lymph node status underwent SLNB in 57 groins after application of a radiotracer (Tc-99 m nanocolloid). We collected the results prospectively. The reliability of the method was assessed by determining the false-negative rate. In addition, we evaluated complication rates and determined the radioactive burden for the clinical staff both pre- and intraoperatively. RESULTS: SLNB was performed in 34 patients with penile cancer with non-palpable inguinal lymph nodes in 57 groins. In two patients inguinal lymph node metastases were detected by means of SLNB. In one patient recurrent inguinal lymph node disease was found after negative SLNB in both groins. Thus, the false negative rate was 3.13 % per patient (1/32 patients) and 3.51 % per groin (2/57 groins). The morbidity rate was 2.94 % per patient (1/34 patients) and 1.75 % per groin (1/57 groins). Radiation exposure for the clinical staff during this procedure was low at a maximum of ca. four µSV per intervention. CONCLUSIONS: SLNB is a reliable method with low morbidity that is associated with a low radiation burden for clinical staff. Due to the enhanced methodological and logistic demands, this intervention should be performed in specialized centres and in an interdisciplinary approach.

Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization.

PURPOSE: Identifying gastroduodenal uptake of (99m)Tc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls. METHODS: Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements. RESULTS: Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver. CONCLUSION: SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind.

Liver Function Changes After Technetium-99m-Macroaggregated Albumin Administration and Their Predictive Value Regarding Hepatotoxicity in Patients Undergoing Yttrium-90-Radioembolization.

BACKGROUND/AIM: Intraarterial Technetium-99m-Macroaggregated Albumin (99mTc-MAA) administration is an established method to predict particle distribution prior to radioembolization. This study aimed to analyse the impact of intraarterial administration of 99mTc-MAA on changes in liver-specific laboratory parameters and to assess whether such changes are associated with post-radioembolization hepatotoxicity. PATIENTS AND METHODS: A total of 202 patients treated with radioembolization received prior mapping angiography with 99mTc-MAA administration. All patients underwent clinical and laboratory examinations, including liver-specific parameters at certain times before and after mapping angiography/99mTc-MAA administration, as well as before radioembolization and during follow-up. RESULTS: Bilirubin increased temporarily after 99mTc-MAA administration (p<0.001), but was not clinically relevant, and returned close to the initial value before radioembolization. These changes showed no association with subsequent postradioembolic hepatotoxicity or shortened overall survival. CONCLUSION: 99mTc-MAA administration results in a significant, however, not clinically relevant transient increase in bilirubin levels, which does not provide a predictive value for subsequent radioembolization outcome or postradioembolic hepatotoxicity.

[Notification of an adverse effect to human albumin (99m)Tc-nanocolloid]. / Notificación de una reacción adversa al (99m)Tc-nanocoloide de albúmina.

Allergic reactions to albumin nanocolloid are rare. Most of them are not potentially serious and in some cases treatment with antihistamines may be needed. We present a case of a patient with grade II right breast ductal carcinoma, in whom a lymphoscintigraphy was performed for sentinel lymph node detection. She had a type I hypersensitivity reaction following the administration of (99m)Tc-albumin nanocolloid, which abated spontaneously without subsequent sequels.

Quantification of Radiation Exposure of Non-Dominant Index for the Surgeon Performing Sentinel Lymph-Node Removal Procedure.

BACKGROUND: Sentinel lymph-node scintigraphy is a useful method for accurate staging of different tumors and a helpful tool in personalized therapy for oncological patients. The radiation exposure for surgical staff has been a concern since the sentinel lymph-node detection method was developed. OBJECTIVE: The objective of the study was to determine and quantify the exposure to radiation of the non-dominant index for the surgeon performing sentinel lymph-node removal and to determine, if there is an irradiation risk imposed during the surgical procedure. METHOD: We performed a study over a period of one year, where we evaluated the exposure of surgeon's non-dominant index during 196 sentinel lymph-node removal procedures. The pharmaceutical was administrated via subcutaneous injection in four peritumoral or perilesional injection sites. The equipment we used consisted of EuroProbe3 for sentinel lymph-node detection and ring TLD dosimeter placed on the surgeon's non-dominant index. RESULTS: The clinical distribution was: 104 melanomas, 84 breast carcinomas, 6 vulvar carcinomas and 2 penial carcinomas. The administered activity showed an average of 39.55 MBq (SD ± 1.96) Tc-99m nanoalbumin compound. The non-dominant index exposure ranged between 0.10 mSv and 0.13 mSv/month with a cumulative dose of 1.31 mSv/year, thus 6.69 µSv per procedure. CONCLUSION: The surgeon received a minimal dose for the non-dominant index. The values we recorded did not pose any additional concerns or restrictions, the exposure being under the limits and constraints established by regulations, close to the detectability limit of the dosimeter. The procedure is safe in terms of radiation protection, respecting the limitation and optimization principles.

Diffusing capacity is not measurably affected by routine lung perfusion scanning.

Lung scanning with radiolabeled macroaggregated albumin (MAA) has caused cardiovascular collapse and death in patients with extensive pulmonary vascular disease. These adverse reactions have been suggested to be secondary to MAA embolic occlusion of a significant portion of the remaining pulmonary circulation. The single breath diffusing capacity for carbon monoxide (SBDLCO) is heavily dependent on the status of the pulmonary microcirculation and is reduced in clinical pulmonary embolism. The effect of MAA particles on the lung microcirculation was measured by SBDLCO in 11 patients undergoing clinically indicated lung perfusion scanning. SBDLCO was measured before and immediately after injection of 256,000 to 448,000 20-40 micron particles of [99mTc]MAA. Mean SBDLCO prior to injection was 18.9 +/- 1.7 (s.e.m.) and immediately after injection was unchanged at 19.0 +/- 1.6 ml/min/mmHg. The lowest pre-injection SBDLCO values were 11.5 and 6.2 ml/min/mmHg (54% and 28% of predicted, respectively); in neither of these patients was there a detectable change in SBDLCO measured after injection of MAA. Thus occlusion of as many as 448,000 20-40 micron pulmonary vessels by MAA is without detectable impact on the transfer of carbon monoxide even in patients with sufficient pulmonary disease to lower the SBDLCO to 28% of predicted.

Radiation protection for the sentinel node procedure in breast cancer.

AIMS: The purpose of our study was to determine the radiation dose for those who are involved in the sentinel node procedure in breast cancer patients and testing of a theoretical model. METHODS: We studied 12 consecutive breast cancer patients undergoing breast surgery, and a sentinel node dissection including an axillary lymph node dissection (ALND). We performed measurements on the surgeon, the assistant, the theatre nurse, the pathologist and his assistant. RESULTS: The measurements on the theatre nurse and both pathologist as his assistant are beneath the detection limit of 10 micro Sv. The highest measured doses are the hands of the surgeon and his assistant (17-61 micro Sv), however the dose limits for hands are higher than for other parts of the body. Taking the dose limits into account the abdominal wall of the surgeon relatively receives the highest dose, with an average of 8.2 micro Sv per procedure. CONCLUSION: Radiation dose levels are less than the established dose limits for (nonexposed) workers if the number of procedures is restricted to about 100/person/year.

Quantitative assessment of the radiation hazards and risks in sentinel node procedures.

Sentinel node localization using an injected radiopharmaceutical and a gamma probe is performed in many hospitals. Employers have a duty to give appropriate training to staff who may not have been previously formally trained to work with unsealed radioactive sources. A study was performed to assess hazards and risks at all stages of the localization procedure. Whole body doses and finger doses of imaging, surgery and pathology staff were determined. The activity remaining in the tumour specimen, excised nodes and disposable waste from the operating theatre was measured. Any radioactive contamination of the operating theatre and equipment was also ascertained. All results were then assessed in light of current UK radiation protection legislation for the protection of staff and members of the public. Results showed that radiation doses are low and no additional procedures are required for protection of staff, provided the usual procedures for biohazards are in place. However, an information sheet has been prepared for the reassurance of staff, and theatre swabs may need to be stored temporarily before disposal. Injecting and imaging on the day before surgery is preferred, compared with injecting and imaging before surgery on the same day, since this gives lower radiation doses to staff, lower activity in excised specimens and waste, and provides a higher count rate giving better image quality.

The incidence and severity of hypoxia associated with 99Tcm Technegas ventilation scintigraphy and 99Tcm MAA perfusion scintigraphy.

Inhalation of the ventilatory radiopharmaceutical 99Tcm Technegas leads, in some patients, to symptoms that may be attributed to temporary lowering of oxygen saturation. In order to evaluate this, oxygen saturation was measured by pulse oximetry in a series of patients undergoing Technegas ventilation scintigraphy. A decrease in oxygen saturation was recorded in 87% of the patient group. The mean change, as a percentage of the initial value, was 8.3% (range 1-24%). Hypoxia arising in association with Technegas administration may be reduced by pre-oxygenation. In patients who were pre-oxygenated, oxygen saturation did not fall below 85% (PaO2: 50 mmHg) but in 39% of those not pre-oxygenated the value fell below this level. Oxygen saturation was also monitored in a series of patients undergoing perfusion scintigraphy. In 17% of patients a decrease was recorded (range 2-11%). In view of the large number of perfusion scans performed annually in this department and elsewhere without untoward effect, such temporary decreases in oxygen saturation presumably present no hazard to the patient.

Arterial oxygen saturation in patients undergoing perfusion lung scanning with 99Tcm-labelled macroaggregates of human serum albumin.

Radionuclide imaging of the lungs with 99Tcm-labelled macroaggregates of human serum albumin (99Tcm-MAA) is a safe, reliable and non-invasive method of diagnosing pulmonary embolism. It has been suggested that following intravenous injection of 99Tcm-MAA, arterial oxygen saturation falls significantly. Oxygen saturation was measured in 101 patients who had received an intravenous injection of 99Tcm-MAA prior to a perfusion lung scan. Readings were taken using a pulse oximeter at rest, immediately following injection, 10, 30 and 60 min post-injection. Twenty-five normal volunteers who were not injected acted as controls. Forty patients showed no change in oxygen saturation throughout the study. A fall of 1% was seen in 32 patients and 2-3% in 26 patients. Of the three patients who demonstrated a reduction in saturation of 6, 7 and 13%, two had chronic airways disease and one had left ventricular failure. Twenty out of 25 normal controls showed no change in saturation over the period of observation. Five showed a fluctuation of 1-2% between the measurements. All patients and controls remained asymptomatic with almost all readings returning to the initial values after 1 h. It was the patients with chest or heart disease who showed a fall in saturation. The study shows that the majority of patients undergoing a perfusion scan with 99Tcm-MAA show no significant fall in oxygen saturation. If a fall occurs, it may be related to the underlying disease process rather than to 99Tcm-MAA.

Arteriovenous shunting of microspheres in patients with colorectal liver metastases: errors in assessment due to free pertechnetate, and the effect of angiotensin II.

In patients receiving locoregional therapy for liver metastases degradable microspheres are being increasingly used in an attempt to improve cytotoxic delivery to the tumour. However, counterproductive arteriovenous shunting through the liver following intrahepatic arterial injection can occur, leading to deposition in the lung. Measurement of the degree of shunting is important in the monitoring of this kind of therapy. In this study we describe the use of technetium-labelled microspheres of serum albumin (99Tcm MSA) to measure baseline shunting during hepatic arterial perfusion scintigraphy in five patients with liver metastases of colorectal origin, and assess the significance of the values obtained for relative lung uptake (RLU) which we define as: RLU = Activity in lung field/Activity in liver + lung fields X 100%. We found that shunting was less than 5% in all cases, zero shunting occurring in 14 of the 16 patients studied. The sources of error in this technique have been assessed, the most important being the presence of free pertechnetate in the injectate. The use of Boots 10 ml vials and glass syringes respectively to dispense and administer this radiopharmaceutical reduces this error to a small predictable level. In our small group of patients, we found no evidence to suggest that use of the vasoactive agent angiotensin II significantly increases baseline shunting in patients with colorectal liver tumour.

Radiolabeled localization of the sentinel lymph node: dosimetric evaluation in personnel involved in the procedure.

AIMS AND BACKGROUND: Peritumoral injection of 99mTc-labeled colloids for lymphoscintigraphy and radioguided surgery does not entail any relevant radiation burden to the patients. The real issue about radiation protection concerns the personnel involved in the procedure besides the nuclear medicine personnel. The aim of our study was to evaluate the cumulative doses to personnel involved during the injection of radiolabeled compounds, under ultrasound or stereotactic guidance and the radiation burden to the personnel involved in the surgical incision of the tumor 24 hours after the administration of 99mTc-labeled colloids. METHODS AND STUDY DESIGN: We performed environmental contamination tests (SMEAR TEST) and exposure evaluation in the operating room. RESULTS: In the operating room the removed activity in the analyzed samples was less than 0.5 Bq/g and exposure to the personnel was less than 6 micro Sv/h. The evaluations made during ultrasound guidance demonstrated an equivalent and effective dose less than 20 microSv. CONCLUSIONS: Our results show that during ultrasound or stereotactic administration of radiolabeled compounds the radiation burden to the personnel involved in the procedure is virtually negligible. The surgeons too are exposed to a negligible radiation dose.

Radioguided surgery of breast cancer: radiation protection survey.

The aim of this study was to estimate the radioactive risk for surgical staff performing radioguided sentinel lymph node (SN) biopsy and to calculate the contamination level in the operating room for assessment of the possible need for specific radiation protection procedures. We studied 20 patients who were selected for quadrantectomy and SN biopsy. The day before surgery a volume of 0.15 mL of 99mTc-nanocoll was injected: the activity was 3.11 +/- 0.85 MBq in group A (15 pts) and 11.6 +/- 0.6 MBq in group B (5 pts). External radiation to staff was evaluated by measuring the exposure rate in air one hour after radiopharmaceutical administration. The air KERMA rate during surgery was estimated considering the physical decay of 99mTc. Contamination of disposable materials and surgical instruments in the operating room was measured using a contamination monitor, whereas the residual activity in the SN and the injection site was measured with a gamma probe. The exposure rate at 20 cm from the injection site was 0.75 microSv/h when the most radioactive patients (group B) were treated. Contamination in the operating room proved to be negligible. Considering the number of radioguided treatments carried out by a surgeon in one year, an equivalent effective dose of 0.075 mSv was estimated; the recommended dose limit according to the relevant Italian law, DL 230/95, is 1 mSv/yr. Surgical staff therefore do not require a classification of "exposed workers" and there is no need to supply the operating room with special containers for radioactive waste.

[Radiation exposure of surgical staff during sentinel node surgery. Is there a risk for the surgeon and his team?]. / Évaluation de l'irradiation du personnel de chirurgie gynécologique lors de la recherche du ganglion sentinelle. Y a-t-il un risque pour le chirurgien et son équipe ?

OBJECTIVE: Assess the radiation exposure of surgical staff during sentinel node surgery in gynecology using a radiotracer, the (99m)Tc-microalbumin. MATERIALS AND METHODS: A monocentric, prospective study was conducted during 3 months representing 40 sentinel node surgical procedures with different dosimetric measurements. Dosimeters were used to evaluate the whole body and the fingers radiation exposure for all exposed workers (surgeon, nurse and surgical assistant). Another dosimeter was used to estimate the atmospheric radiation level. The activity of (99m)Tc-microalbumin was 50.1±2.4MBq when the surgery was performed the same day and 90.4±3.2MBq when the surgery was performed the day after. RESULTS: Radioactive doses received during each procedure by the surgeon, surgical assistant and nurse are 5, 3.75 and 0µSv for whole body exposure and 17.5, 15.6 and 16.2µSv for extremities respectively. Atmosphere dosimeter does not detect any radiation over this period. On average, 200 procedures are performed each year in our hospital by 7 surgeons. Surgeon's radiation exposure remains below the threshold of 1mSv annual for whole body and 50mSv annual for fingers set for public by the International Commission on Radiological Protection. DISCUSSION AND CONCLUSIONS: During sentinel node surgery radiation exposure of surgical staff is weak. Everyone, including the surgeon, receives a dose below the limits of the public radiation exposure. There is no need for special dosimetric monitoring or use radiation protective devices during the sentinel node surgery using (99m)Tc-microalbumin injection.

Photodynamic therapy of the canine prostate: intra-arterial drug delivery.

PURPOSE: Interstitial photodynamic therapy (PDT) selectively destroys tissue targeted with a photosensitizer and then exposed to light of a specific wavelength. We report a novel delivery method--intra-arterial drug delivery for PDT of the prostate--in a canine model. METHODS: To evaluate drug distribution, the prostatovesical artery was selectively cannulated and photosensitizers alone or in conjunction with 99m-technetium-labeled macro-aggregated albumin ((99m)Tc-MAA) were injected via a 3 Fr microcatheter in 8 animals. One dog was followed for 3 months to determine tolerance and toxicity. The remaining animals were euthanized and imaged with whole-body single photon emission CT and gamma counting for radioactivity distribution. Photosensitizer distribution was further analyzed by fluorescence confocal microscopy and tissue chemical extraction. To evaluate PDT, the photosensitizer QLT0074 was infused in 3 animals followed by interstitial illumination with 690 nm laser light. RESULTS: Intra-arterial infusion selectively delivered drugs to the prostate, with both radioactivity and photosensitizer levels significantly higher (up to 18 times) than in the surrounding organs (i.e., rectum). With unilateral injection of (99m)Tc-MAA, only the injected half of the prostate showed activity whereas bilateral administration resulted in drug delivery to the entire prostate. PDT resulted in comprehensive damage to the prostate without severe complications or systemic toxicity. CONCLUSION: Injection of radiolabeled MAA into the prostatovesical artery results in distribution within the prostate with negligible amounts reaching the adjacent organs. PDT also demonstrates selective damage to the prostate, which warrants clinical application in targeted prostate therapies.