Characteristic Single Photon Emission Computed Tomography-Computed Tomography Findings in Lower Extremity Lymphedema: Comparison to Indocyanine Green Lymphography.

Introduction: Evaluation of lymph circulation is significant in lower extremity lymphedema (LEL) management. Single-photon emission computed tomography-computed tomography (SPECT-CT) has been introduced for lymphedema evaluation, but its characteristic findings are yet fully clarified. The purpose of this study was to reveal typical SPECT-CT findings in secondary LEL by contrasting with indocyanine green (ICG) lymphography findings. Methods: This is a single-center retrospective case-control study. Medical charts of cancer survivors who underwent SPECT-CT and ICG lymphography for secondary LEL were reviewed. Lymphedematous limbs were defined as ICG lymphography stage I-V and non-lymphedematous limbs were defined as ICG lymphography stage 0. Characteristic SPECT-CT findings were identified in early phase and delay phase, and prevalence of the findings was compared between lymphedematous limbs and non-lymphedematous limbs. Results: Thirty-four limbs of 17 patients were included in this study; 6 (17.6%) non-lymphedematous limbs and 28 (82.4%) lymphedematous limbs. Four characteristic SPECT-CT findings were identified; delayed enhancement of the main lower leg lymphatic pathway (DML), few delayed inguinal lymph nodes enhancement (FDN), early phase discontinuous enhancement of the main lymphatic pathway (EDM), and nonenhancement of the deep lymphatic pathways in early phase (NDE). Between lymphedematous and non-lymphedematous limbs, there were statistically significant differences in FDN (64.3% vs. 0%, p = 0.004) and EDM (67.9% vs. 0%, p = 0.002). Conclusions: FDN and EDM are characteristic SPECT-CT findings in secondary LEL.

Progression of fluid infiltration on non-contrast magnetic resonance imaging in breast cancer-related lymphedema: A comparative analysis with indocyanine green lymphography.

BACKGROUND: Non-contrast magnetic resonance imaging (NMRI) has been reported as valuable for the assessment of lymphedema. However, the correlation between NMRI findings and indocyanine green lymphography (ICG-L) findings remains elusive. METHODS: This single-center retrospective study included 26 patients diagnosed with breast cancer-related lymphedema. We examined the prevalence of fluid infiltration in eight regions of the upper extremity, the type of fluid distribution, and the dominant segment of edema on NMRI in comparison to the ICG-L stage. Statistical analysis was performed using the Cochran-Armitage trend test, Spearman's rank correlation test, and Fisher's exact test. RESULTS: The regional fluid infiltration significantly increased with the progression of the ICG-L stage (hand, forearm, elbow, and upper arm: p = 0.003, <0.001, <0.001, and <0.001, respectively). The fluid distribution significantly advanced with the progression of the ICG-L stage as follows (rs = 0.80; p < 0.001): no edema in ICG-L stage 0, edema in either the hand or elbow in ICG-L stage I, edemas in both the elbow and hand in ICG-L stage II, three segmental edemas centered on the forearm or elbow in ICG-L stage III, and edema encompassing the entire upper limb in ICG-L stage IV-V. Additionally, the dominant segment of edema tended to shift from the hand to the elbow and further to the forearm as the ICG-L stage progressed (p < 0.001). CONCLUSIONS: Fluid infiltration observed on NMRI exhibited distinct patterns with the progression of the ICG-L stage. We believe that anatomical information regarding fluid distribution would potentially contribute to optimizing surgical efficacy.

Three-dimensional non-contrast magnetic resonance lymphography severity stage for upper extremity lymphedema.

PURPOSES: Non-contrast magnetic resonance lymphography (NMRL) has recently shown the capability of evaluating anatomical fluid distribution in upper extremity lymphedema (UEL). However, there is still a lack of knowledge about the correlation between the characteristic three-dimensional (3D) NMRL findings and the indocyanine green lymphography (ICG-L) findings. Our goal was to clarify the relationship between the 3D NMRL findings and the ICG-L findings. METHODS: Medical charts of patients with secondary UEL who underwent NMRL and ICG-L between January 2018 to October 2021 were reviewed. The upper extremities were divided into 6 regions; the hand, elbow, and the radial and ulnar aspects of the forearm and the upper arm. We investigated the prevalence of characteristic 3D NMRL patterns (Mist/Spray/Inky) in each region based on the ICG-L stage. We also examined the association between the 3D NMRL stage which we proposed and the ICG-L stage, and other clinical factors. RESULTS: A total of 150 regions of 25 patients with upper extremities lymphedema were enrolled in the study. All of the characteristic patterns increased significantly as the ICG-L stage advanced (p < 0.001, < 0.001, and < 0.001, respectively). The predominant NMRL patterns changed significantly from the Early pattern (Mist pattern) to the Advanced pattern (Inky/Spray pattern) as the ICG-L stage progressed (p < 0.001). The higher Stage of 3D NMRL was significantly associated with the progression of the ICG-L stage (rs = 0.80, p < 0.001). CONCLUSIONS: Characteristic 3D NMRL patterns and the 3D NMRL Stage had a significant relationship with the ICG-L stage and other clinical parameters. This information may be an efficient tool for a more precise and objective evaluation of various treatments for UEL patients.

Dermal-adipose lymphatic flap venous wrapping: A novel lymphaticovenous shunt method for progression of upper extremity lymphedema with severe lymphosclerosis.

BACKGROUND: Upper extremity lymphedema (UEL) causes a significant deterioration in the quality of life of breast cancer survivors. Lymphaticovenous shunt creation will address the pathophysiology of obstructive UEL; however, its efficacy has been limited for those with UEL progression due to lymphosclerosis. In the present study, we evaluated the feasibility of a new lymphaticovenous shunt method for progression of UEL. METHODS: A total of 37 patients who had undergone dermal-adipose lymphatic flap venous wrapping (DALF-VW) for the treatment of UEL progression refractory to previous lymphaticovenular anastomosis were included. A DALF was created where indocyanine green lymphography had shown dermal backflow and was wrapped with a reflux-free recipient vein. The patients' medical records were reviewed to obtain the clinical and intraoperative findings. The patient and vessel characteristics and postoperative results were evaluated. RESULTS: A total of 37 patients with unilateral UEL were included. All DALF-VW procedures were performed under local infiltration anesthesia, with 98 shunts created in 37 limbs (2.6 shunts per limb). The diameter of the vein used for DALF-VW ranged from 1.7 to 3.3 mm (average, 2.39 mm). The operative time ranged from 25 to 139 minutes (average, 47.8 minutes). The differences in the lymphedema quality of life score (45.6 ± 21.1 vs 32.5 ± 21.1; P = .009), UEL index (131.4 ± 18.2 vs 123.1 ± 16.4; P = .042), and frequency of cellulitis (0.8 ± 1.3 vs 0.2 ± 0.5 times annually; P = .010) before and after DALF-VW were statistically significant. CONCLUSIONS: DALF-VW was effective for UEL progression that was refractory to previous lymphaticovenular anastomosis surgery. DALF-VW could be a useful option for UEL progression with severe lymphosclerosis.

Anti-proliferating and apoptosis-inducing activity of chemical compound FTI-6D in association with p53 in human cancer cell lines.

Compounds with 3,4-fused tricyclic indole (FTI) frameworks are attractive scaffolds for drug discovery. We synthesized FTI-6D, a compound with this framework, which was cytotoxic in several human cancer cell lines. FTI-6D induced apoptosis via activation of the p53 downstream mitochondria-related apoptotic pathway, characterized by an increased ratio of pro-apoptotic Bcl-2 family members to anti-apoptotic members. This change was followed by caspase-9 and caspase-3 cleavage and activation in two cancer cell lines, RKO and AGS. The anti-proliferating effect of FTI-6D was remarkably detected in eight cancer cells with wild-type TP53 (TP53_wt), including RKO and AGS, but not in seven cancer cells with mutated TP53 (TP53_mut). Additionally, p53 protein levels increased after FTI-6D treatment in TP53_wt cancer cells, and the cytotoxic effect of FTI-6D was decreased by TP53 knockdown. Accordingly, the expression of p53 downstream genes involved in apoptotic signaling pathways, such as BBC3 and TP53INP1, and those involved in cell growth inhibition, such as CDKN1A, was upregulated in TP53_wt cancer cells. These results suggest that the anti-proliferative and apoptosis-inducing activities of FTI-6D rely on p53 and the corresponding signaling processes. This study demonstrated that FTI-6D shows anti-cancer activity against TP53_wt cancer cells. FTI-6D may have potential as a prototype compound for a new drug to utilize a functional p53 pathway in TP53_wt cancer cells.

Surgical treatment for a rare case of duodenal gangliocytic paraganglioma accompanied with lymph node metastasis.

We report a rare case of duodenal gangliocytic paraganglioma accompanied with lymph node metastasis. An asymptomatic 58-year-old woman was admitted for the evaluation of abnormal liver enzyme test results. Abdominal computed tomography and upper gastrointestinal endoscopy revealed a 27-mm pedunculated tumor of the papilla of Vater. Adenocarcinoma of the papilla with muscularis propria invasion was suspected; therefore, pancreaticoduodenectomy with lymph node dissection was performed. There were no perioperative complications. A definitive diagnosis of gangliocytic paraganglioma of the papilla of Vater with lymph node metastases was confirmed by pathological examinations, which is a rare condition. The patient was discharged on her 16th postoperative day, and no recurrence or metastases were identified during the 18-month follow-up period. We herein discuss the surgical treatment for this rare case and present a review of related literature.

Nerve vascularity in free vascularized nerve flaps.

The blood supply of peripheral nerves consists of a complex internal vessels' network, feeding external vessels and the interlinking vasa nervorum. Patients with nerve damage may require nerve substitution. While the commonly performed avascular nerve grafts obtain vascularization only from random and slow inosculation into the vasa nervorum, their insufficient revascularization causes loss of the graft's potential due to central necrosis. This gets more relevant with the larger diameter of nerves injured. Examples for neurovascular flaps are the lateral femoral cutaneous nerve vascularized via the superficial circumflex iliac artery perforator (LFCN-SCIP) flap or the iliohypogastric nerve graft vascularized via the superficial inferior epigastric artery (SIEA). LFCN-SCIP shows a well concealed donor scar site with a maintained vascularization and a minor donor site morbidity. Therefore, the guaranteed axial nerve vascularity in LFCN-SCIP makes it a preferred autologous vascularized nerve therapy for peripheral nerve defects. A further option example is the anterior lateral thigh (ALT) flap with the LFCN.