This study included an initial 28 consecutive patients with lower extremity lymphedema who underwent unilateral lymphedema surgery at our institution between September 2009 and April 2020. Among them, 3 patients without preoperative lymphoscintigraphy and 1 patient without a preoperative volume evaluation record were excluded. One patient receiving only liposuction but not LVA was excluded, and 3 patients with bilateral lymphedema were excluded. One patient with follow-up loss after surgery and 2 patients with other venous or rheumatologic disease were excluded. Finally, 17 patients with lower extremity edema were enrolled. All subjects underwent maintenance physical therapy after LVA according to individual clinical situation. This study was approved by the Institutional Review Board of Samsung Medical Center on 24 June 2021 (IRB File No. SMC 2021-06-148), and informed consent was waived due to the retrospective design.
Lymphoscintigraphic Imaging Acquisition And Analysis
A total of 148 MBq of 99mTc-tin colloid or 99mTc-phytate was injected into the first and second web spaces between the toes of both feet of the patient. Anterior and posterior images of both lower extremities were obtained immediately after the injection (at 0 min) and, at 1 h and at 2 h using a dual-headed gamma camera (e-cam, Siemens Healthineers, Erlangen, Germany). Patients were encouraged to walk for 15 min after immediate post-injection imaging to promote lymphatic drainage. Quantitative indicators were obtained by setting regions of interest (ROIs) on both legs in the 1 h and 2 h delayed images. Lymph node (LN) uptake (%), extremity uptake (%), and injection site clearance (%) were calculated as follows.
LN uptake (%) = 100 x (ilioinguinal LN site count at 1 h or 2 h)/(injection site count at 0 min)
Extremity uptake (%) = 100 x (extremity count at 1 h or 2 h)/(injection site count at 0 min)
Injection site clearance (%) = 100 x (injection site count at 0 min - injection site count at 1 h or 2 h)/(injection site count at 0 min)
Visual analysis regarding the presence of ilioinguinal LN uptake, visualization of the main lymphatic vessel, visualization of the collateral vessel, and presence of dermal backflow was performed by two nuclear medicine physicians who were unaware of clinical information. Regarding the radiopharmaceutical used, there was no significant difference in diagnostic performance between tin colloid and phytate (17).
Clinical And Imaging Variables
Age, sex, clinical stage, etiology, preoperative volume evaluation of the whole leg, and postoperative volume evaluation of the whole leg (at 3 months and 1 year after surgery) were obtained as clinical indicators. In addition, history of inflammation before and after surgery was confirmed because of its impact on prognosis (18). These data were obtained through review of electronic medical records. Postoperative volume change was assessed as the volume difference ratio ((preoperative volume minus postoperative volume)/preoperative volume). Volume change after 3 months was regarded as early response, and change after 1 year was indicated as late response. Volume difference ratio was analyzed not only as a continuous variable, but also as a dichotomous treatment response with a cut-off value of zero. A volume difference ratio below 0 was considered a volume increase, and a volume difference ratio above 0 was considered a volume decrease.
Imaging indicators were categorized as qualitative and quantitative. As qualitative indicators, ilioinguinal LN uptake, main lymphatic vessel, collateral vessel, and dermal backflow were evaluated by a binary method (absent/present). Dermal backflow was additionally classified into the ‘Distal only’ pattern, ‘Proximal only’ pattern, and ‘Whole leg (proximal & distal)’ pattern according to site [Figure 1]. As quantitative indicators, the ratio of edematous limb/healthy limb of each lymphoscintigraphic parameter was used for consideration of individual variance of each absolute value.
Because the patient group was a small cohort and did not satisfy normality, all analyses were conducted in a non-parametric manner. Mann-Whitney test was used to evaluate the relationships between qualitative indicators and volume difference ratio. Fisher's extract test was used to evaluate the relationships between qualitative indicators and dichotomous response. Spearman’s rank correlation was used to evaluate the relationships between quantitative indicators and volume difference ratio. Mann-Whitney test was used to evaluate the relationships between quantitative indicators and dichotomous response. The pattern of dermal backflow was evaluated based on three patterns: absent; distal only OR proximal only; whole leg. The Jonckheere Terpstra test was performed to determine the trend in volume difference ratio among the 3 groups, and linear by linear association was performed to determine the trend in dichotomous response among the 3 groups. IBM SPSS Statistics software (version 27.0) was used for analyses, and a p-value less than 0.05 was considered statistically significant.