Clinical Significance Of Dermal Backflow On Lymphoscintigraphy In Patients With Lower Limb Edema.

Chronic blockage of the lymphatic system due to functional or anatomical causes results in lymphoedema which results in swelling due to accumulation of lymphatic fluid in the soft tissue. Lymphoedema commonly affects the upper and lower limbs but may be seen in the neck, chest wall, abdomen and genitalia. Lymphoscintigraphy is non-invasive and maps the lymphatic channels thereby indicating location of blockage along the lymphatic pathways. Blockage of lymphatic channels may lead to back pressure resulting in dermal backflow. We present a case of dermal backflow in bilateral lymphoedema.

Short term treatment of secondary lymphedema with hyaluronidase injections reduces mouse hindlimb lymphedema.

Lymphedema is a common complication following breast cancer treatment with axillary lymphadenectomy and radiotherapy. Currently, there is no curative treatment for this disease, hence there is a need for new therapeutic suggestions. The aim of this study was to investigate the effect of hyaluronidase (HYAL) injections after inducing hindlimb lymphedema in 36 female C57BL/6 mice. HYAL injections were administered every second day for 14 days in three groups: (1) HYAL for 1 week followed by saline for 1 week, (2) HYAL for 2 weeks, and (3) saline injections for 2 weeks. Volume of the lymphedema limb was weekly assessed with micro-computed tomography (µ-CT) scans for a total course of 6 weeks. Lymph vessel morphometry was assessed in the end of the study after staining cross-sections of the hindlimb for anti-LYVE-1 blindly. Lymphatic function was assessed by lymphoscintigraphy to assess lymphatic clearance. There was a significant reduction of the volume of lymphedema in mice treated with HYAL-7 compared with mice treated with HYAL-14 (p < 0.05) and saline (p < 0.05). No differences were detected in lymph vessel morphometry and the lymphoscintigraphy between groups. Short-term treatment with HYAL-7 might be a potential therapeutic suggestion for secondary lymphedema induced in mouse hindlimbs. In the future, clinical studies are needed to investigate the potential of HYAL treatment in human beings.

Imaging biomarkers for diagnosis and treatment response in patients with lymphedema.

Lymphedema is defined as a dysfunction of the lymphatic system producing an accumulation of lymphatic fluid in the surrounding tissue, as well as edema and fibrosis. A total of 250 million people worldwide are affected by this condition. Greater than 99% of these cases are related to a secondary cause. As there is a lack of curative therapy, the goal involves early diagnosis, in order to prevent the progression of the disease. Additionally, early diagnosis can aid in decreasing the demand for more complex surgical procedures. Currently, there is an impressive breadth of diagnostic tests available for these patients. We aimed to review the available literature in relation to the utilization of imaging biomarkers for the early diagnosis and treatment response in lymphedema.

Buffering the Suffering of Breast Lymphoscintigraphy.

Breast lymphoscintigraphy with 99mTc-sulfur colloid is frequently performed before breast-conserving surgery to delineate drainage to a sentinel node. Tracer injection for lymphoscintigraphy can be painful. Our aims were to determine whether administering a solution of buffered lidocaine immediately before lymphoscintigraphy injection could both reduce the patients' pain and increase nuclear medicine technologists' satisfaction with performing the procedure. Methods: A pain scale survey was obtained from patients undergoing breast lymphoscintigraphy with or without buffered lidocaine. Our nuclear medicine technologists were also surveyed for their satisfaction with the procedure, both with and without the addition of buffered lidocaine. Results: The patients' reported pain decreased by 86% with the addition of buffered lidocaine. Technologist satisfaction with performing the procedure increased by 36%. Conclusion: Lidocaine buffered with sodium bicarbonate injected before lymphoscintigraphy significantly reduces pain experienced by the patient and improves nuclear medicine technologist satisfaction in performing the procedure.

Lymphoscintigraphy for Imaging of the Lymphatic Flow Disorders.

Lymphoscintigraphy has introduced with the great advantage for diagnostic imaging of the lymphatic flow disorders. Lymphoscintigraphy can be performed in patients of any age, including neonates, and even in patient in critical conditions. The procedure is quite simple, and it needs only subcutaneous injection of small amounts of radiotracers. From subcutaneous tissue the radiotracer is taken by the lymphatic vessels and gives off energy in the form of gamma radiation detected by a gamma camera. Radiotracers rarely cause the allergic reaction and can be administered to the patients with allergy to iodine contrast media. Comparing with the Lipiodol, radiotracers cannot cause pulmonary embolism; therefore, it is safe for the patients with respiratory dysfunction. The objective of this article is to describe the indication, technique, equipment, pitfalls, safety, and effectiveness of lymphoscintigraphy for imaging of the lymphatic flow disorders.

Comparison of Post-injection Site Pain Between Technetium Sulfur Colloid and Technetium Tilmanocept in Breast Cancer Patients Undergoing Sentinel Lymph Node Biopsy.

BACKGROUND: No prior studies have examined injection pain associated with Technetium-99m Tilmanocept (TcTM). METHODS: This was a randomized, double-blinded study comparing postinjection site pain between filtered Technetium Sulfur Colloid (fTcSC) and TcTM in breast cancer lymphoscintigraphy. Pain was evaluated with a visual analogue scale (VAS) (0-100 mm) and the short-form McGill Pain Questionnaire (SF-MPQ). The primary endpoint was mean difference in VAS scores at 1-min postinjection between fTcSC and TcTM. Secondary endpoints included a comparison of SF-MPQ scores between the groups at 5 min postinjection and construction of a linear mixed effects model to evaluate the changes in pain during the 5-min postinjection period. RESULTS: Fifty-two patients underwent injection (27-fTcSC, 25-TcTM). At 1-min postinjection, patients who received fTcSC experienced a mean change in pain of 16.8 mm (standard deviation (SD) 19.5) compared with 0.2 mm (SD 7.3) in TcTM (p = 0.0002). At 5 min postinjection, the mean total score on the SF-MPQ was 2.8 (SD 3.0) for fTcSC versus 2.1 (SD 2.5) for TcTM (p = 0.36). In the mixed effects model, injection agent (p < 0.001), time (p < 0.001) and their interaction (p < 0.001) were associated with change in pain during the 5-min postinjection period. The model found fTcSC resulted in significantly more pain of 15.2 mm (p < 0.001), 11.3 mm (p = 0.001), and 7.5 mm (p = 0.013) at 1, 2, and 3 min postinjection, respectively. CONCLUSIONS: Injection with fTcSC causes significantly more pain during the first 3 min postinjection compared with TcTM in women undergoing lymphoscintigraphy for breast cancer.

Reducing perceived pain levels during nonbreast lymphoscintigraphy.

PURPOSE: The aim of this study was to quantify the reduction of perceived pain levels during lymphoscintigraphy for melanoma by altering the pH of the Tc-sulfur colloid to near the physiologic value of 7.40. PATIENTS AND METHODS: This is an institutional review board- and Food and Drug Administration-approved randomized, double-blinded, prospective crossover trial, registered with clinicaltrials.org. Before beginning the procedure and after signing informed consent, 60 serial enrollees presenting for sentinel lymph node imaging of melanoma of the thorax and appendicular structures completed a questionnaire addressing background information, administered by a research support nurse.An investigator (N.H.) prepared the injections to be used and labeled them such that no one else could discover which injections contained standard-of-care solution and which contained the pH-altered solution (buffered to near pH 7.40 using sodium bicarbonate).After each injection, the enrollee was asked by a research support nurse to quantify the pain of each injection using a scale of 0 to 10. The injection site location (head, thorax, appendicular structures, and other) was also recorded. RESULTS: Sixty subjects were enrolled in the study, of which 57 had complete data. On average, there was a significant mean (SD) decrease of 1.42 (2.17) points (95% confidence interval, 0.85-2.00) on a pain scale of 0 to 10 when the buffered injections were used as compared with the standard-of-care injections (P < 0.0001). Ordering of injections did not significantly affect perceived pain scores. CONCLUSIONS: The use of sodium bicarbonate to buffer the pH of Tc-sulfur colloid to near the physiologic value of 7.40 significantly reduced perceived pain levels during nonbreast lymphoscintigraphy.

EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma.

PURPOSE: Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized melanoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with melanoma. METHODS: These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, national nuclear medicine societies, the European Society of Surgical Oncology (ESSO) and the European Association for Research and Treatment of Cancer (EORTC) melanoma group. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI). CONCLUSION: The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of melanoma patients.

Could sentinel node mapping of the groin cause extranodal metastasis in vulva cancer?

Groin node lymphadenectomy in vulva cancer carries a substantial risk of morbid sequelae. Sentinel lymph node (SLN) mapping is a valid alternative in patients with squamous cancer of diameter <4 cm and nonsuspicious lymph nodes. SLN are mapped according to the combined technique of radioscintigraphy using technetium-labelled colloid and blue dye. We describe early extranodal recurrence in 2 patients undergoing SLN mapping. They had lymph node metastases at their original dissection. We question whether rapid lymph flow promoted by injection of colloid and dye could cause retrograde flow of cancer cells along the lymphatics draining from the pubis to the groin and extravasation of cancer cells into the dermis since these metastases arose anterior to the pubis and medial to the groin. These recurrence sites were more medial and cephalad than would be expected for skin bridge metastasis. CT imaging shows the metastases are within the dermis. No lymphatic tissue was identified around these subcuticular cancer deposits at repeat resection. Body wall extension occurs in recurrent vulva cancer, but we never saw such an early recurrence when full inguinofemoral lymphadenectomy without SLN was the standard approach. These 2 cases raise a caveat in the application of SLN mapping in vulva cancer, especially when metastasis is detected on SLN as the afferent channels to the lymph nodes may be already blocked or flow impaired by the tumour.

Administration of subcutaneous buffered lidocaine prior to breast lymphoscintigraphy reduces pain without decreasing lymph node visualization.

UNLABELLED: Breast lymphoscintigraphy using (99m)Tc-sulfur colloid ((99m)Tc-SC) is well established in clinical practice for staging patients with breast carcinoma. Nearly all patients report having pain during the procedure. However, techniques used to minimize pain during breast lymphoscintigraphy are highly variable across institutions. Our study was to determine whether anesthetizing the skin with sodium bicarbonatehether-buffered lidocaine before performing breast lymphoscintigraphy reduced the pain experienced by the patients. The second objective of this study was to evaluate whether anesthetizing the skin with buffered lidocaine changed visualization of lymph nodes. METHODS: This prospective, patient-masked and randomized study involved performing breast lymphoscintigraphy in a control group and experimental group of female breast cancer patients. The control group did not receive skin anesthetic before (99m)Tc-SC injections, whereas the experimental group first underwent skin anesthesia with an injection of 2% sodium bicarbonate-buffered lidocaine. All patients were asked to rate their pain levels, using the National Institutes of Health pain scale, before the procedure and immediately after the injections. The change in pain from baseline was compared between the 2 groups. After the injections, scintigraphic imaging of the axilla was performed, and the number of axillary lymph nodes visualized was recorded. RESULTS: No significant difference was found in preprocedural baseline pain from the control group, compared with the experimental group. There was a statistically significant difference in the increase in pain experienced during the procedure between the control group and the experimental group (P = 0.009). There was no significant difference in the detection of lymph nodes between the control and experimental groups (P = 0.56). CONCLUSION: The results from our study indicate that injecting subcutaneous buffered lidocaine before intradermal injection of (99m)Tc-SC for breast lymphoscintigraphy significantly decreases patient pain without interfering with lymph node visualization.

"Stocking effect" in lymphoscintigraphy.

Lymphoscintigraphy following subcutaneous injection of a radiolabeled macromolecule, such as Tc-99m-nanocolloid, is used to investigate limb swelling, usually to confirm lymphedema. A well-known abnormal finding is dermal backflow, which occurs a result of diversion of lymph into skin lymphatic vessels. We describe a case in which this important sign was partially obscured by a stocking. The case also illustrates, first, the frequent though poorly recognized occurrence of lymphatic dysfunction in the clinically normal contralateral limb of a patient with unilateral swelling, and second, the principle underlying treatment with compression hosiery. Stockings should be removed before injection and all subsequent imaging.

Sentinel lymph node status in vulval cancer: systematic reviews of test accuracy and decision-analytic model-based economic evaluation.

BACKGROUND: Vulval cancer causes 3-5% of all gynaecological malignancies and requires surgical removal and inguinofemoral lymphadenectomy (IFL). Complications affect > 50% of patients, including groin wound infection, lymphoedema and cellulitis. A sentinel lymph node (SLN) is the first groin node with the highest probability of malignancy. SLN biopsy would be useful if it could accurately identify patients in whom cancer has spread to the groin, without removing all groin nodes. SLNs can be identified by isosulfan blue dye and/or technetium-99 ((99m)Tc) radioactive tracer during lymphoscintigraphy. The blue dye/(99m)Tc procedure only detects SLN, not metastases - this requires histological examination, which can include ultrastaging and staining with conventional haematoxylin and eosin (H&E) or immunohistochemistry. OBJECTIVES: To determine the test accuracy and cost-effectiveness of the SLN biopsy with (99m)Tc and/or blue dye compared with IFL or clinical follow-up for test negatives in vulval cancer, through systematic reviews and economic evaluation. DATA SOURCES: Standard medical databases, including MEDLINE, EMBASE, Science Citation Index and The Cochrane Library, medical search gateways, reference lists of review articles and included studies were searched to January 2011. METHODS: For accuracy and effectiveness, standard methods were used and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were to January 2011, with no language restrictions. Meta-analyses were carried out with Meta-Disc version 1.4 (Javier Zamora, Madrid, Spain) for accuracy; none was appropriate for effectiveness. The economic evaluation from a NHS perspective used a decision-tree model in DATA TreeAge Pro Healthcare 2001 (TreeAge Software, Inc., Williamstown, MA, USA). Six options (blue dye with H&E, blue dye with ultrastaging, (99m)Tc with H&E, (99m)Tc with ultrastaging, blue dye/(99m)Tc with H&E, blue dye/(99m)Tc with ultrastaging) were compared with IFL. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: For accuracy, of the 26 included studies, most evaluated (99m)Tc/blue dye combined. Four studies had clinical follow-up only for test negatives and five had clinical follow-up for all and IFL for test negatives. Numbers with no SLN found were difficult to distinguish from those with negative SLN biopsies. The largest group of 11 studies using (99m)Tc/blue dye, ultrastaging and immunohistochemistry had a pooled sensitivity of 95.6% [95% confidence interval (CI) 91.5% to 98.1%] and a specificity of 100% (95% CI 99.0% to 100%). Mean SLN detection rates were 94.6% for (99m)Tc, 68.7% for blue dye and 97.7% for both. One study measured global health status quality of life (QoL) and found no difference between SLN biopsy and IFL. One patient preference evaluation showed that 66% preferred IFL rather than a 5% false-negative rate from SLN biopsy. For effectiveness, of 14,038 references, one randomised controlled trial, three case-control studies and 13 case series were found. Approximately 50% died from vulval cancer and 50% from other causes during follow-ups. Recurrences were in the ratio of approximately 4 : 2 : 1 vulval, groin and distant, with more recurrences in node-positive patients. No studies reported QoL. For cost per death averted, IFL was less costly and more effective than strategies using SLN biopsy. For morbidity-free survival and long-term morbidity-free survival, (99m)Tc with ultrastaging was most cost-effective. Strategies with blue dye only and H&E only were never cost-effective. The incremental cost-effectiveness ratio for (99m)Tc with ultrastaging compared with IFL was £4300 per case of morbidity-free survival and £7100 per long-term morbidity-free survival. LIMITATIONS: The main limitations of this study include the lack of good-quality evidence on accuracy, effectiveness and QoL. A large project such as this takes time to publish, so the most recent studies are not included. CONCLUSIONS: A sensitive and specific combined metastatic SLN detection test and information on generic QoL in vulval cancer is urgently required. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Reliability of a radiological grading system for dermal backflow in lymphoscintigraphy imaging.

RATIONALE AND OBJECTIVES: Lymphoscintigraphy may be used for diagnosing secondary lymphedema. Dermal backflow, the presence of radiotracer in dermal lymphatics, is a key clinical feature. Although often reported as present or absent, a scale that assesses the severity of dermal backflow has been previously developed. The aim of this study was to determine the reliability of these two methods of assessment. MATERIALS AND METHODS: Sixteen experienced nuclear medicine physicians assessed the quantity of dermal backflow of 57 lymphoscintigraphy scans using a 4-point descriptive scale that was dichotomized for secondary analysis. Each scan included images from four time points for women previously diagnosed with secondary lymphedema (n = 47) and controls (n = 5); five scans were presented twice to examine intraobserver reliability. This was further investigated as 13 physicians viewed the scans again on an Apple iPad2. The physicians rated their confidence in their scoring. Readers were blinded to clinical history. RESULTS: Although both the 2- and 4-point scale had moderate interobserver reliability, the reliability of the 2-point scale was slightly higher (4-point: Fleiss κ = .418, standard error [SE] = .008); 2-point: Fleiss κ = .574, SE = .013). Low interobserver reliability was found when only control subjects were considered (Fleiss κ = 0.055, SE = 0.034). Intraobserver reliability of the five repeated images varied from poor to perfect (Cohen κ = .063 to 1.00), whereas moderate to substantial intraobserver reliability (Cohen's κ = .342 to .752) was found when comparing devices. The readers were highly confident of their scores. CONCLUSIONS: Overall, moderate intraobserver and interobserver reliability was found for quantifying dermal backflow with both the 2- and 4-point scale.

[Lymphoprostatic scintigraphy in regional lymphatic mapping in patients with prostate cancer].

The purpose of the investigation was to upgrade the diagnosis quality for metastatic lesion to the regional lymp nodes in prostate cancer. The results of the most widely used diagnostic techniques (computed tomography (CT), magnetic resonance Imaging, (MRI), radionuclide studies (RNS), and ultrasonography (USG)), which had been compared with those of histology of removed lymph nodes, were assessed. For this, 74 patients with prostate cancer were comprehensively examined and treated at the Central Research X-ray Radiolological Institute. The comparative assessment of radiodiagnostic techniques (USG, CT, MRI, and RNS) showed the high informative value of retroperitoneal lymph nodal MRI in the detection of structural-and-morphological and anatomic-and-topographic changes in the lymph nodes (87.5% sensitivity, 83.3% specificity, and 85.7% accuracy). The developed lymphoprostatic scintigraphy (LPSG) is an informative technique that allows the better diagnosis of prostate metastases to the regional lymph nodes (92.4% sensitivity, 91.7% specificity, and 92.1% accuracy; the prognostic value of a positive result is 90.7%). LPSG is superior in its informative value to small pelvic USG and CT and inferior to indirect lymphoscintigraphy and yields valuable additional information on the physiological function of the small pelvic lymphatic collector.