Sentinel lymph node detection in thyroid carcinoma using [68Ga]Ga-tilmanocept PET/CT: a proof-of-concept study.

PURPOSE: Sentinel lymph node (SLN) biopsy is rarely used for thyroid carcinoma staging. This is due to challenges associated with conventional Tc-99m-labeled tracers, often producing a large hotspot at the injection site, potentially hiding nearby SLNs (shine-through effect). The aim of this study was to demonstrate the feasibility and effectiveness of SLN visualization using the new PET tracer [68Ga]Ga-tilmanocept. METHODS: Patients with thyroid carcinoma underwent ultrasound-guided peritumoral injection of [68Ga]Ga-tilmanocept and ICG-[99mTc]Tc-nanocolloid. [68Ga]Ga-tilmanocept PET/CT scans were conducted at 15 min and 60 min post-injection to visualize the SLNs. SLN biopsy was performed using ICG-[99mTc]TC-nanocolloid for intraoperative identification. The corresponding lymph node level was resected for reference. RESULTS: Seven differentiated thyroid carcinoma (DTC) and 3 medullary thyroid carcinoma (MTC) patients were included, of which 6 were clinically node-negative. The median number of SLNs detected on [68Ga]Ga-tilmanocept PET/CT and resected was 3 (range 1-4) and 3 (range 1-5), respectively. Eight SLNs were found on PET/CT in the central compartment and 19 in the lateral compartment. The SLN procedure detected (micro)metastases in all patients except one. Seventeen of 27 pathologically assessed SLNs were positive, 8 negative, and 2 did not contain lymph node tissue, which led to upstaging in 5 out of 6 clinically node-negative patients. CONCLUSIONS: [68Ga]Ga-tilmanocept PET/CT identified SLNs in all patients, mainly in the lateral neck. The SLNs were successfully surgically detected and resected using ICG-[99mTc]Tc-nanocolloid. This technique has the potential to improve neck staging, enabling more personalized treatment of thyroid cancer according to the lymph node status. TRIAL REGISTRATION: 2021-002470-42 (EudraCT).

La linfogammagrafía in vivo de los tumores del seno nasal identifica el ganglio retrofaríngeo y el nivel I como ganglios centinela predominantes / In-vivo lymphoscintigraphy of sinonasal tumors identifies retropharyngeal node and level I as predominant sentinel nodes

Objetivo Evaluar mediante linfogammagrafía in vivo y con detección SPECT/TC los patrones de drenaje linfático de los tumores del seno paranasal (SPN). Confirmar o rebatir la creencia de que el ganglio linfático retrofaríngeo (GLRF) se erige en el ganglio de drenaje índice para dichos tumores. Métodos Estudio de cohorte prospectivo realizado en pacientes con tumores del SPN no tratados previamente y sin evidencia clínico-radiológica de metástasis a nivel ganglionar. La linfogammagrafía se realizó mediante la inyección peritumoral de sulfuro coloidal marcado con [99m]TcO4 y asistida por endoscopia nasal. Las inyecciones se clasificaron como anteriores o posteriores en función de una línea vertical que pasaba por el orificio del seno maxilar. Resultados Se incluyeron 17 pacientes. La linfogammagrafía identificó satisfactoriamente 17 ganglios centinelas en 15 pacientes, y no pudo evidenciarlo (fracaso de la linfogammagrafía) en 2 pacientes. Se observó que los lugares predominantes de drenaje del ganglio centinela fueron el GLRF (n=8; 47%) y el nivel I (n=7; 42%). Se identificó drenaje ocasional en el ganglio periparotídeo (n=1) y en el nivel II (n=1). Se observó drenaje linfático contralateral en 2 pacientes (en el nivel I y GLRF, respectivamente). Las inyecciones anteriores drenaron predominantemente hacia el nivel I (6/8) y a GLRF (2/8), mientras que las inyecciones posteriores drenaron predominantemente a GLRF (6/7). El riesgo relativo de que el GLRF fuera identificado como ganglio centinela fue significativamente mayor en las inyecciones administradas posteriormente respecto a las administradas anteriormente (RR: 3,43; IC 95%: 1,0-11,8; p=0,05). Conclusión El GLRF es considerado un ganglio de drenaje frecuente asociado a los tumores del seno nasal, y merece su atención rutinaria en todos los casos de tumor del seno nasal (AU)

Objective To evaluate by in vivo lymphoscintigraphy and SPECT-CT imaging, the lymphatic drainage patterns of para-nasal sinus (PNS) tumours. To confirm or refute the belief of the retropharyngeal lymph node (RPLN) being the significant draining lymph node for such tumours. Methods Prospective cohort study conducted on previously untreated PNS tumours with no clinico-radiological evidence of lymph node metastasis. Lymphoscintigraphy undertaken by nasal endoscopic assisted peritumoral injection of 99mTc sulphur colloid. Injections were classified as anterior or posterior as per a vertical line along the maxillary sinus ostium. Results Seventeen patients were included. Lymphoscintigraphy successfully identified 17 sentinel nodes in 15 patients and was unsuccessful (lymphoscintigraphy failure) in 2 patients. Predominant sites of sentinel lymphatic drainage were noted to be the RPLN (n=8; 47%) and level I (n=7; 42%). Occasional drainage was identified at the peri-parotid node (n=1) and at level II (n=1). Contralateral drainage was noted in 2 patients (level I-1 and RPLN-1). Anterior injections drained predominantly to level I (6/8) and RPLN (2/8), while posterior injections drained predominantly to the RPLN (6/7). The relative risk of RPLN being identified as the sentinel node was significantly higher for posteriorly placed injections than for anteriorly placed injections (RR: 3.43; 95% CI: 1.0-11.8; P=.05). Conclusion The RPLN is noted as a frequent draining node for sino-nasal tumours and merits routine attention in all sino-nasal tumours. The radio-colloid SPECT-CT technique described here offers an excellent in vivo technique to further explore and validate the lymphatic drainage pathways of these tumours (AU)

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.

Quantitative lymphoscintigraphy of the lower limbs for the diagnosis of phlebolymphoedema.

INTRODUCTION: Phlebolymphoedema is caused by the interaction of the venous and lymphatic systems in a state of chronic venous insufficiency in which increased microvascular filtration causes an increased rate of lymph production. Lymphatic drainage rate increases in response, but this is unsustainable and can cause lymphatic failure and oedema. We hypothesise that in phlebolymphoedema we could measure unusually high lymphatic drainage while the lymph system is still fully functional. METHOD: Patients referred for lymphoscintigraphic investigation of swollen legs between April 2021 and December 2022 were reviewed. Quantitative lymphoscintigraphy was performed following the technique of Keramida et al . (2017) and ilio-inguinal nodal uptake (IIQ%) was calculated. The presence of scintigraphic features of increased lymph production was noted for each limb. RESULTS: A total of 39 patients were reviewed (78 limbs, 29F, 10M). Seven limbs were identified with supranormal lymphatic function (IIQ > 30%) plus three borderline. Of these 10 limbs, all had at least two scintigraphic features of increased lymph production. CONCLUSION: Quantitative lymphoscintigraphy, although developed for diagnosing abnormally low lymphatic function, may also have utility at the upper end of the spectrum for identifying chronic venous insufficiency. An IIQ% upper normal limit of 30% could be used to diagnose venous insufficiency as the cause for limb swelling. This is of note for patients of large body habitus in whom venous ultrasound is difficult.

Radioactive nanosized colloids and indocyanine green identify the same sentinel lymph nodes in oral squamous cell carcinoma.

PURPOSE: Near-infrared fluorescence imaging using indocyanine green (ICG) combined with radioactive markers has the potential to improve sentinel lymph-node (SLN) mapping in oral squamous cell carcinoma (OSCC). This study aimed to evaluate the ability of 99mTc and ICG in identifying the sentinel lymph nodes in patients with early stage OSCC. METHODS: Data were collected prospectively, and a retrospective analysis of 15 patients with early stage OSCC and a cN0 neck was performed. All patients received peritumoral injection of 99mTc the day before surgery and ICG was administered intraoperatively. Intentionally, the application of the two different tracers were done by two different physicians with varying degrees of experience. The number of identified lymph nodes positive for 99mTc and ICG, the overlap or possible discrepancies of both methods, and the time until fluorescence signals of ICG were detected were noted. RESULTS: In all patients, a 100% agreement in sentinel lymph-node identification was achieved, regardless of both the exact location of the peritumoral injection and the experience of the injecting surgeon. Time until ICG accumulation in the sentinel lymph node was consistently found to be between 1 and 3 min. CONCLUSION: ICG constitutes a viable and useful addition to 99mTc for intraoperative sentinel lymph-node detection in this study.

Sentinel lymph node procedure in early-stage vulvar cancer: Correlation of lymphoscintigraphy with surgical outcome and groin recurrence.

INTRODUCTION: In early-stage vulvar squamous cell carcinoma (VSCC) a sentinel lymph node (SLN) procedure is regarded successful if at least one SLN is removed with minimal residual radioactivity. An inguinofemoral lymphadenectomy is considered if not all SLNs visualized on lymphoscintigraphy can be found, with subsequent increased morbidity. We correlated lymphoscintigraphy findings with surgical outcome and groin recurrence with focus on number of SLNs found. METHODS: This study concerns a retrospective cohort of 171 women treated for early-stage VSCC who underwent a SLN procedure between 2000 and 2020. The risk of groin recurrence was compared after either a successful or complete SLN procedure, i.e. removal of all SLNs that were visualized on lymphoscintigraphy. RESULTS: In 13 (7.6%) groins of 171 patients SLN visualization on lymphoscintigraphy failed. In 230 of the 246 (93.5%) groins in which a SLN was visualized, at least one SLN was found during surgery. In 224 of the 246 (91.1%) groins the SLN procedure was regarded either successful (n = 14) or complete (n = 210). An isolated groin recurrence was documented in 5 out of 192 (2.6%, 95%-CI; 0.34 to 4.9) SLN-negative groins after a median follow-up of 47.0 months. All recurrences were noted in the complete SLN group (5/180 groins). The difference with the successful SLN group (0/12 groins) was not significant. CONCLUSION: Risk of groin recurrence was 2.6% after SLN negative biopsy in early-stage VSCC. The risk appeared not increased if at least one SLN was found with minimal residual radioactivity, in case more SLNs were visualized on lymphoscintigraphy.

In-vivo lymphoscintigraphy of sinonasal tumors identifies retropharyngeal node and level I as predominant sentinel nodes.

OBJECTIVE: To evaluate by in- vivo lymphoscintigraphy and SPECT-CT imaging, the lymphatic drainage patterns of para-nasal sinus(PNS) tumors. To confirm or refute the belief of the retropharyngeal lymph node (RPLN) being the significant draining lymph node for such tumors. METHODS: Prospective cohort study conducted on previously untreated PNS tumors with no clinico-radiological evidence of lymph node metastasis. Lymphoscintigraphy undertaken by nasal endoscopic assisted peritumoral injection of 99mTc Sulfur colloid. Injections were classified as anterior or posterior as per a vertical line along the maxillary sinus ostium. RESULTS: 17 patients were included. Lymphoscintigraphy successfully identified 17 sentinel nodes in 15 patients and was unsuccessful (lymphoscintigraphy failure) in 2 patients. Predominant sites of sentinel lymphatic drainage were noted to be the RPLN (n = 8; 47%), and Level I (n = 7; 42%). Occasional drainage was identified at the peri-parotid node(n = 1) and at Level II (n = 1). Contralateral drainage was noted in 2 patients (level I-1 and RPLN-1). Anterior injections drained predominantly to Level I (6/8) and RPLN (2/8), while posterior injections drained predominantly to the RPLN ( 6/7). The relative risk of RPLN being identified as the sentinel node was significantly higher for posteriorly placed injections than for anteriorly placed injections (RR- 3.43; 95% CI-1.0-11.8, p = 0.05). CONCLUSION: The RPLN is noted as a frequent draining node for sino-nasal tumours and merits routine attention in all sino-nasal tumors. The radio-colloid SPECT-CT technique described here offers an excellent in-vivo technique to further explore and validate the lymphatic drainage pathways of these tumours.

Pneumatic Compression-Assisted Lymphoscintigraphy for Quantitative Evaluation of Breast Cancer-Related Lymphedema.

OBJECTIVES: Acquired lymphedema of upper extremity is a chronic pathologic status that frequently occurs after breast cancer treatment. Reliable and quantitative evaluation of lymphedema is crucial for successful management of patients. Although lymphoscintigraphy is the primary investigation for the confirmation and evaluation of lymphedema, the specific protocol of stress intervention is not well established. This study aims to introduce intermittent pneumatic compression (IPC) as a part of stress lymphoscintigraphy and compare the effectiveness of conventional stress lymphoscintigraphy (CSL) and pneumatic compression-assisted lymphoscintigraphy (PCAL). METHODS: Our study was designed as a retrospective analysis of 85 breast cancer patients with lymphedema who underwent lymphoscintigraphy utilizing either IPC device or conventional stress maneuver and received complex decongestive therapy. The flow extent of the lymphatic fluid (FE) was evaluated using a 0- to 4-point scale based on lymphoscintigraphic images. The visualization of lymph nodes was also assessed. The clinical outcomes were evaluated by changes in side-to-side circumferential and volume differences of upper extremities and compared between groups. RESULTS: Of 85 patients, 47 underwent CSL, and 38 underwent PCAL. Participants with relatively preserved flow extent of the lymphatic fluid (FE 3) showed a significant difference in percentage reduction of volume (PRV) between CSL and PCAL groups ( P = 0.036). In the other groups, CSL and PCAL demonstrated comparable differences in PRV without statistical significance. CONCLUSION: Our study suggests that participants in the PCAL group with relatively preserved lymphatic flow extent (FE 3) had better PRV compared with those in the CSL group. The use of IPC devices in lymphoscintigraphy with the novel stress maneuver can help in the quantitative description of lymphedema status and the selection of an appropriate treatment method.

Validation of single-photon emission computed tomography with computed tomography and lymphoscintigraphy for sentinel lymph node identification in cervical cancer.

OBJECTIVE: To compare single-photon emission computed tomography with computed tomography (SPECT/CT) and lymphoscintigraphy (LSG) for the detection of sentinel lymph nodes (SLNs) in patients with early-stage cervical cancer. METHODS: This hospital-based, single-center, retrospective study included 128 patients with cervical cancer (aged >18 years) treated between 2014 and 2022. Injection of 99 m Technetium-labeled phytate into the uterine cervix was used to detect pelvic SLNs. SNL identification rates and locations were analyzed for preoperative LSG and SPECT/CT. RESULTS: Median age and body mass index of patients were 40 years (range, 20-78 years) and 21.7 kg/m2 (range, 16-40 kg/m2 ), respectively. There was no significant difference in overall identification rates (identification of at least one SLN) of SLNs between SPECT/CT (91%) and LSG (88%). There was no significant difference in bilateral SLN identification rates between SPECT/CT (66%) and LSG (65%). A total of 219 pelvic SLNs (110 right and 109 left hemipelvis) were identified by SPECT/CT; the most frequent locations were the obturator (122 SLNs, 56%) and external iliac (67 SLNs, 30%). CONCLUSION: SPECT/CT and LSG showed high SLN identification rates in patients with cervical cancer, and there was no significant difference in overall or bilateral SLN identification rates between the two techniques.

Investigating a Technologist-Driven Injection Technique in Lymphoscintigraphy at a Single Rural Center: A Retrospective Audit.

Our aim was to investigate the effectiveness of the technologist-driven injection technique of lymphoscintigraphy used at a rural hospital in Australia to identify the correct lymph node for sentinel lymph node biopsy (SLNB) in early-stage breast cancer patients. Methods: A retrospective audit was conducted using imaging and medical record data from 145 eligible patients who underwent preoperative lymphoscintigraphy for SLNB at a single center throughout 2013 and 2014. The lymphoscintigraphy technique included a single periareolar injection with subsequent dynamic and static images as required. Descriptive statistics, sentinel node identification rates, and imaging-surgery concordance rates were generated from the data. Additionally, χ2 analysis was used to examine the relationships between age, previous surgical intervention, and injection site and time until a sentinel node is visualized. The technique and statistical results were directly compared against multiple similar studies in the literature. Results: The sentinel node identification rate was 99.3%, and the imaging-surgery concordance rate was 97.2%. The identification rate was significantly higher than those of similar studies in the literature, and concordance rates were similar across studies. The findings demonstrated that age (P = 0.508) and previous surgical intervention (P = 0.966) did not influence the time it takes to visualize a sentinel node. Injection site did appear to have a statistically significant effect (P = 0.001), with injections in the upper outer quadrant correlating with increased times between injection and visualization. Conclusion: The reported lymphoscintigraphy technique for identifying sentinel lymph nodes for SLNB in early-stage breast cancer patients can be justified as an accurate and effective method that is time-sensitive and has outcomes comparable to those of successful studies in the literature.

Evaluation of sentinel lymph node localization in malignant melanoma by preoperative semiconductor gamma camera and planar lymphoscintigraphy.

INTRODUCTION: Performing lymphoscintigraphy in a separate room, frees up the conventional gamma camera, coupled with the desire to directly localize sentinel lymph nodes (SLN) in the operating theatre has led to the development of high-resolution semiconductor-detector based handheld gamma-cameras, CrystalCam. METHODS: This work consists of phantom and clinical studies. For the first part, a Jaszczak phantom with hollow spheres of various volumes were filled with the 99m Tc and the camera's sensitivity was measured at various distances to assess the possibilities and limitations of the device. The clinical study evaluates the effectiveness of CrystalCam in localizing SLN in 40 consecutive malignant melanoma patients compared to both conventional planar lymphoscintigraphy and hybrid SPECT/CT. SLNs detected by planar lymphoscintigraphy were marked on the patients' skin using a UV-marker. CrystalCam images were acquired in another room by another examiner and the SLNs were marked with a felt pen. The detected nodes by both camera systems were evaluated using UV-lamp and normal light to visualize the UV- and felt pen marks respectively. The concordance rate of the SLNs and higher-echelon nodes localized by both planar scintigraphy and CrystalCam imaging with respect to the total SLNs and higher-echelon nodes detected by SPECT/CT imaging are compared and statistically analyzed. RESULTS: The results of the phantom study show a good correlation between activity and count-rates for all distancesSPECT/CT, CrystalCamm, and planar lymphoscintigraphy detected 69, 58, and 61 SLNs respectively. The concordance rate of 95.65% by the CrystalCam and planar scintigraphy implies both cameras are statistically coequal in preoperative SLN detection of malignant melanoma. For the higher-echelon nodes, SPECT/CT, planar and CrystalCam imaging systems identified 82, 48, and 13 respectively; thus, CrystalCam was statistically inferior to planar imaging. CONCLUSION: The handheld CrystalCam is a reliable instrument for localizing SLNs in surgical centers without an on-site nuclear medicine department.

The impact of sentinel lymph node mapping with hybrid single photon emission computed tomography/computed tomography in patients with melanoma. Comparison to planar radioisotopic lymphoscintigraphy.

We studied the diagnostic value of 16 slices of single photon emission computed tomography (SPECT)/computed tomography (CT) in the anatomical localization, image interpretation and extra-sentinel lymph nodes (SLNs) detection compared to dynamic and static planar radioisotopic lymphoscintigraphy (PLS) in patients with melanoma. Eighty-two patients with melanoma underwent dynamic PLS, static PLS and SPECT/CT. Data were obtained using a dual head SPECT/CT 16 slices γ-camera. We evaluated the number and localization of SLNs detected with each imaging method. SPECT/CT demonstrated 48 additional SLNs in comparison with PLS in 29 patients. In five truncal and seven head-neck lesions, dynamic and static PLS failed to detect the SLNs found on SPECT/CT (false negative). In one case of truncal and one case of lower limb melanoma, the foci of increased activity interpreted on PLS as possible SLNs were confirmed to be non-nodal sites of uptake on SPECT/CT (false positive). PLS underestimated the number of SLNs detected, whereas SPECT/CT revealed higher agreement compared to the respective number from histological reports. SPECT/CT showed a better prediction of the number of SLNs and higher diagnostic parameters in comparison to planar imaging. SPECT/CT is an important complementary diagnostic modality to PLS, that improves detection, preoperative evaluation, anatomical landmarks of SLNs and surgical management of patients with melanoma.

A pilot study of lymphoscintigraphy with tracer injection into the human brain.

Many groups have reported lymphatic and glymphatic structures in animal and human brains, but tracer injection into the human brain to demonstrate real-time lymphatic drainage and mapping has not been described. We enrolled patients undergoing standard-of-care resection or stereotactic biopsy for suspected intracranial tumors. Patients received peritumoral injections of 99mTc-tilmanocept followed by planar or tomographic imaging. Fourteen patients with suspected brain tumors were enrolled. One was excluded from analysis because of tracer leakage during injection. There was no drainage of 99mTc-tilmanocept to regional lymph nodes in any of the patients. On average, after correcting for radioactive decay, 70.7% (95% CI: 59.9%, 81.6%) of the tracer in the injection site and 78.1% (95% CI: 71.1%, 85.1%) in the whole-head on the day of surgery remained the morning after, with variable radioactivity in the subarachnoid space. The retained fraction was much greater than expected based on the clearance rate from non-brain injection sites. In this pilot study, the lymphatic tracer 99mTc-tilmanocept was injected into the brain parenchyma, and there was no drainage outside the brain to the cervical lymph nodes. Our work demonstrates an inefficiency of drainage from peritumoral brain parenchyma and highlights a therapeutic opportunity to improve immunosurveillance of the brain.

Lymphoscintigraphy Using Tilmanocept Detects Multiple Sentinel Lymph Nodes in Melanoma Patients.

BACKGROUND: Technetium-99m-labeled Tilmanocept, a multivalent mannose, is readily internalized by the CD206 surface receptor on macrophages and dendritic cells which are abundantly present in lymph nodes. We want to examine the drainage patterns of Technetium-99m-labeled Tilmanocept to sentinel lymph nodes (SLNs) in melanoma patients following the 10% rule. METHODS: Multi-center retrospective review of patients with cutaneous melanoma undergoing SLN biopsy using Technetium-99m-labeled Tilmanocept between 2008 and 2014 was conducted. Statistical methods were used for data analyses. RESULTS: Of the 564 patients (mean age of 60.3 and 62% male) with preoperative lymphoscintigraphy showing at least one SLN, several primary tumor sites were included: 27% head/neck, 33% trunk, 21% upper extremity and 19% lower extremity. For the head/neck primary site, 36.5% of patients had multiple draining basins; for the trunk site, 36.4% of patients; for the upper extremity site, 13% of patients; and for the lower extremity, 27.4% of patients. A median of 3 (range 1-18) SLNs were identified and resected. Overall, 78% of patients had >1 SLN identified by Technetium-99m-labeled Tilmanocept. In a multivariate model, patients with >1 SLN were significantly associated with age, Breslow depth, tumor location and higher AJCC tumor stage. A total of 17.7% of patients (100/564) had a positive SLN identified. A total of 145 positive SLNs were identified out of 1,812 SLNs with a positive SLN rate of 8%. Positive SLN status was significantly associated with younger age, greater Breslow depth, mitosis rate, higher AJCC tumor stage, presence of ulceration and angiolymphatic invasion. CONCLUSIONS: Using the 10% rule, Technetium-99m-labeled Tilmanocept detects multiple SLNs in most melanoma patients.

Detection of sentinel lymph node in vulvar cancer using 99mTc-labeled colloid lymphoscintigraphy, blue dye, and indocyanine-green fluorescence: a meta-analysis of studies published in 2010-2020.

OBJECTIVES: Sentinel lymph node (SLN) biopsy is widely accepted in the surgical staging of early vulvar cancer, although the most accurate method for its identification is not yet defined. This meta-analysis aimed to determine the technique with the highest pooled detection rate (DR) for the identification of SLN and compare the average number of SLNs detected by planar lymphoscintigraphy (PL), single-photon emission computed tomography/computed tomography (SPECT/CT), blue dye and indocyanine green (ICG) fluorescence. METHODS: The meta-analysis was conducted according to the PRISMA guideline. The search string was: "sentinel" and "vulv*", with date restriction from 1st January 2010 until Dec 31st, 2020. Three investigators selected studies based on: (1) a study cohort or a subset of a minimum of 10 patients with vulvar cancer undergoing either PL, SPECT/CT, blue-dye, or ICG fluorescence for the identification of SLN; (2) the possibility to extrapolate the DR or the average number of SLNs detected by a single technique (3) no evidence of other malignancies in the patient history. RESULTS: A total of 30 studies were selected. In a per-patient and a per-groin analysis, the DR for SLN of PL was respectively 96.13% and 92.57%; for the blue dye was 90.44% and 66.21%; for the ICG, the DR was 91.90% and 94.80%. The pooled DR of SPECT/CT was not calculated, since only two studies were performed in this setting. At a patient-based analysis, no significant difference was documented among PL, blue dye, and ICG (p = 0.28). At a per-groin analysis, PL and ICG demonstrated a significantly higher DR compared to blue dye (p < 0.05). The average number of SLNs, on a per-patient analysis, was available only for PL and ICG with a median number of 2.61 and 1.78 lymph nodes detected, respectively, and no significant statistical difference. CONCLUSIONS: This meta-analysis favors the use of ICG and PL alone and in combination over blue dye for the identification of the SLN in vulvar cancer. Future studies may investigate whether the combined approach allows the highest DR of SLN in patients with vulvar cancer.

Modified Lymphoscintigraphy in Primary Lymphatic Insufficiency of the Lower Limb.

Primary lymphedema of the foot and toes could be sometimes misdiagnosed by lymphoscintigraphy as a whole lower limb lymphatic insufficiency (LLLI). This is caused by using standard lymphoscintigraphic protocol based on one interstitial injection of radiotracer applied into the first interdigital space followed by image analysis of lower limb lymphatic vessels and lymph nodes. Here, we show that a modification of the lymphoscintigraphic protocol and introduction of a second dose of radiotracer right above the inner ankle to the clinically healthy tissue can more accurately describe morphological abnormalities of the superficial lymphatic system at the lower limb and thereby refine the diagnosis of the LLLI. Fourteen patients with swelling of the foot and toes (16 lower limbs) were examined using standard lymphoscintigraphic protocol. Subsequently, modified lymphoscintigraphy was performed. While standard lymphoscintigraphy showed severe lymphatic insufficiency of the superficial lymphatic system in all 14 patients (in 16 lower limbs), including significantly reduced number of inguinal nodes, modified lymphoscintigraphy revealed almost normal morphology of superficial lymphatic vessels in 11 patients (in 13 lower limbs) throughout the entire lower limb proximal to the application site. In conclusion, using the modified lymphoscintigraphy protocol in patients with foot and toes primary lymphedema can refine diagnosis and follow-up medical management.

Rest/Stress Intradermal Lymphoscintigraphy for the Functional Imaging of the Lymphatic System.

PURPOSE: Lymphoscintigraphy is the criterion-standard method for diagnosing lymphedema, and there is no universally standardized imaging modality. In our center, we use a new approach: rest/stress intradermal lymphoscintigraphy. METHODS: We tested 231 consecutive patients with suspected lymphedema. All patients were studied after a complex physical therapy program to reduce edema. Two doses of 99m Tc-nanocolloid were injected intradermally. Two static planar scans were taken at rest following tracer injection. Next, patients performed an isotonic muscular exercise for 2 minutes followed by postexercise scans. Subsequently, a prolonged exercise was performed for 30 to 40 minutes, after which delayed scans were taken. Abnormal patterns were distinguished into minor or major findings, according to severity. RESULTS: We identified superficial lymphatic vessels and regional lymph nodes in approximately 80% of limbs. Deep vessels were visualized in 26% of limbs. Minor findings were reported in 22.7% of limbs examined, whereas major findings were reported in 53.2% of limbs. CONCLUSION: We observed major findings including lymph stagnation, extravasation, or dermal backflow in a significantly higher percentage of limbs with secondary lymphedema than in primary. We also observed the deep lymphatic pathways in a significantly higher percentage of limbs with primary lymphedema. Intradermal radiotracer injection, combined with isotonic muscular exercise, may offer a better and faster imaging of lymphatic pathways, evaluating the effects of muscular exercise on lymphatic drainage. Based on the in-depth information of the lymphatic pathways provided by rest/stress intradermal lymphoscintigraphy, microsurgeons can obtain important functional information to perform supermicrosurgical lymphatic-venous anastomosis or vascularized lymph node transfer.

Preoperative detection of sentinel lymph node in patients with endometrial cancer - comparison of planar lymphoscintigraphy, spect and SPECT/CT.

BACKGROUND: Sentinel lymph node (SLN) mapping allows minimal invasive assessment of lymph node status in patients with early-stage endometrial cancer (EC). Intraoperative detection of SLNs is based on the results obtained from preoperative nuclear medical images. The purpose of this study was to compare the data obtained from planar lymphoscintigraphy (PL), single-photon emission computed tomography (SPECT), and SPECT with computed tomography (SPECT/CT) for preoperative SLN detection in patients with EC. MATERIAL AND METHODS: A total of 44 images in 22 patients with early-stage EC (22 PL, 9 SPECT and 13 SPECT/CT) were analyzed. The scans were performed in the period 2018-2020 at the Institute of Pathophysiology and Nuclear Medicine in Skopje. Thirteen patients underwent PL and SPECT/CT and nine patients underwent PL and SPECT after cervical injection of 4 mCi 99mTc-SENTI-SCINT on the day of surgery. Descriptive statistics, Wilcoxon Matched Pairs Test, and Spearman rank R coefficient were used for data analyses. RESULTS: Twenty-two patients with mean age of 61.1 ± 7.5 and body mass index (BMI) 34.62 ± 6.4 kg/m2 were included in the study. In four patients (18.2%) SLN was not detected on PL. Detection rate on SPECT and SPECT/CT was 100%. The average number of detected SLN was 1.4 ± 1.05, 2.2 ± 1.1 и 2.15 ± 1.1 on PL, SPECT and SPECT/CT respectively. We found a statistically significant difference in the number of detected SLNs on PL vs SPECT/CT (p = 0.0077). The most common SLN location on SPECT/CT was the right internal iliac followed by the left common iliac region. CONCLUSIONS: The results of the presented study indicate a higher diagnostic value of SPECT/CT in terms of SLN detection and exact anatomic localization as compared to planar lymphoscintigraphy (PL).

Photoacoustic lymphangiography is a possible alternative for lymphedema staging.

OBJECTIVE: Photoacoustic imaging is a new technique that uses the photoacoustic effect. In photoacoustic lymphangiography (PAL), images of the lymphatic vessels can be visualized using light-absorbing contrast agents. In the present study, we investigated the efficacy of PAL for lymphedema staging. METHODS: We performed PAL of the lower extremities and examined the clinical implications of using PAL for staging lymphedema by comparing the PAL images with those obtained using lymphoscintigraphy. Of 47 patients with lymphedema who had been outpatients or hospitalized at our institution between May 2018 and September 2020 and had undergone PAL, 15 with 18 limbs who had also undergone lymphoscintigraphy were included in the present study. The lymphoscintigraphy findings were classified using the Maegawa classification. We also investigated whether PAL could clearly visualize the lymphatic vessels and concisely reflect the disease state by counting the number of lymphatic vessels observed using PAL. RESULTS: The PAL findings were categorized into three groups: collecting lymphatic vessels, dermal backflow (DBF), and no lymphatic vessels. The collecting lymphatic vessels group corresponded to types 2 and 3 in the Maegawa classification; DBF corresponded to types 3 and 4, and the no lymphatic vessels group corresponded to type 4. The number of lymphatic vessels visualized using PAL was similar to that with lymphoscintigraphy. As the disease progressed, the number of lymphatic vessels observed decreased, increased DBF was detected, and, eventually, the lymphatic vessels were not visible, corresponding to the general changes observed via lymphoscintigraphy with stage progression. CONCLUSIONS: The findings from PAL and lymphoscintigraphy tended to correspond, suggesting that PAL could be useful for lymphedema staging.