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Vascularized lymph node transfer (VLNT) is an advanced surgical approach for secondary lymphedema (SLE) treatment, but tissue fibrosis around the lymph node flap (VLNF) inhibiting lymphangiogenesis is the biggest challenge undermining its therapeutic efficacy. This study explored the effects of periodic hyaluronidase (HLD) injection in reducing fibrosis and promoting lymphangiogenesis in 52 Sprague-Dawley rats with a VLNF over 13 weeks. The results demonstrated that HLD administration significantly enhanced swelling reduction, lymphatic drainage efficiency, and lymphatic vessel regeneration, with up to a 26% decrease in tissue fibrosis around the VLNF. These findings suggest that combining VLNT with periodic injections of HLD could substantially improve SLE treatment outcomes in clinical settings. It offers a promising direction for future therapeutic strategies and drug development aimed at increasing the efficacy of surgical treatment for SLE patients., (© 2024. The Author(s).)

Background and Objective: Rehabilitation therapy plays an important role in treating physical and functional impairments observed in individuals undergoing hematopoietic stem cell transplants (HSCT). This study assessed the rehabilitation practices implemented in the HSCT population internationally., Materials and Methods: A 48-question online survey comprising questions soliciting information regarding patient characteristics, therapy details (timing, indication, and administering providers), outcome measures, and precautions were developed by an international group of cancer rehabilitation physicians. As reported by European registries, surveys were administered to personnel providing care to patients receiving HSCT at cancer centers, which comprised the top 10% of HSCT volume. In addition, emails were sent to National Medical Societies and registries in the Latin America, Asia, and Pacific regions., Results: Forty-three institutions from 18 countries responded to the survey. Half of the centers provided referrals for rehabilitation therapy at the time of admission. Referrals were provided for functional decline (84.5%), risk of falls (53.3%), and discharge planning (42.2%). Rehabilitation therapies were administered by physical therapists (93.0%), occupational therapists (34.9%), therapy aides (14.0%), and speech-language pathologists (11.6%). Approximately 95% of the surveyed centers used objective functional measures such as sit-to-stand (46.5%), grip strength (46.5%), and 6-min walk/gait speed (both 34.9%). The blood counts were monitored to determine the appropriateness of the therapy modalities., Conclusion: Rehabilitation practices varied internationally; however, most centers provided skilled therapy during hospitalization for HSCT, utilized objective and patient-reported outcomes, and monitored blood counts to determine the safety of administering therapy., (Copyright © 2024 Hematology/Oncology and Stem Cell Therapy.)

Purpose: Assessing the severity of breast cancer-related lymphedema (BCRL) requires various clinical tools, yet no standardized methodology is available. Ultrasonography shows promise for diagnosing lymphedema and evaluating its severity. This study explored the clinical utility of ultrasonography in patients with BCRL., Methods: In this retrospective cross-sectional study, patients with unilateral BCRL were examined. The analyzed data included demographics, lymphedema location, International Society of Lymphology (ISL) stage, surgical history, treatment regimens, and arm circumference. Skin, subcutis, and muscle thicknesses were assessed ultrasonographically at predetermined sites, and the percentage of excess thickness was calculated. Multivariate logistic regression analysis was employed to identify associations between ultrasonographic measurements and advanced lymphedema (ISL 2 or 3). The Lymphedema Quality of Life arm questionnaire was used to evaluate patient-reported outcomes regarding lymphedema and their correlations with ultrasonographic findings., Results: Among 118 patients, 71 were classified as ISL 0-1 and 47 as ISL 2-3. Patients with advanced lymphedema were older, had higher nodal stages, underwent more axillary lymph node dissections, and had higher rates of dominant-arm lymphedema. Multivariate logistic regression revealed significant associations of greater skin thickness (adjusted odds ratio [OR], 4.634; 95% confidence interval [CI], 1.233 to 17.419), subcutis thickness (adjusted OR, 7.741; 95% CI, 1.649 to 36.347), and subcutis echogenicity (adjusted OR, 4.860; 95% CI, 1.517 to 15.566) with advanced lymphedema. Furthermore, greater skin thickness (P=0.016) and subcutis echogenicity (P=0.023) were correlated with appearance-related discomfort., Conclusion: Ultrasonographic measurements were significantly associated with advanced lymphedema in BCRL. Ultrasonography represents a valuable diagnostic and severity assessment tool for lymphedema.

The mammalian target of rapamycin (mTOR) inhibitors are used to prevent organ transplant rejection and are preferred over other immunosuppressants due to its low nephrotoxicity. However, mTOR inhibitors have been associated with various adverse effects including lymphedema. Although rare in incidence, previously known treatments for mTOR inhibitor-induced lymphedema were limited to discontinuation of related drugs and complex disruptive therapy with variable results. In this article, three patients who developed lymphedema in their lower limbs after using mTOR inhibitors, including two bilateral and one unilateral case, were treated with physiologic surgery methods such as lymphovenous anastomosis (LVA) and lymph node transfer. The efficacy of the treatment was evaluated. In the three cases described, cessation of the drug did not lead to any reduction in edema. The use of LVA and lymph node transfer resulted in early reductions in volume but failed to sustain over time. All patients underwent secondary nonphysiologic surgery such as liposuction resulting in sustained improvement. This series presents the first physiologic approach to mTOR inhibitor-induced lymphedema. Although further study is warranted, the physiologic surgical options may have limited success and nonphysiologic options may offer better sustainable results., Competing Interests: Conflict of Interest H.P.S. and J.P.H. are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

The purpose of the study is to investigate long-term changes on lymphoscintigraphy and their association with clinical factors in breast cancer-related lymphedema (BCRL) patients. This single-center cohort study included BCRL patients who underwent baseline and follow-up lymphoscintigraphy. The percentage of excessive circumference (PEC) of the affected upper limb compared with the unaffected side was used as an indicator of the clinical severity of BCRL. Each 99m Tc-phytate lymphoscintigraphy image was categorized according to the Taiwan lymphoscintigraphy staging system. Clinical parameters and the lymphoscintigraphy stage at baseline and follow-up were compared and analyzed. Eighty-seven patients were included. Baseline and follow-up lymphoscintigraphies were performed at median 7 (interquartile range [IQR]: 2‒14) and 78 (IQR: 49‒116) months after surgery, respectively. Both lymphoscintigraphy stage and PEC showed variable change with overall increases in their severity. Stepwise multivariable analysis revealed follow-up lymphoscintigraphy stage (P = 0.001) to be independent variables for PEC at follow-up, however, baseline lymphoscintigraphy stage was not. The clinical courses of BCRL and patients' lymphoscintigraphy patterns showed diverse changes over long-term follow-up. In addition to initial lymphoscintigraphy for diagnosis, lymphatic remapping by follow-up lymphoscintigraphy can be useful to visualize functional changes in the lymphatic system that may guide the optimal management in BCRL., (© 2024. The Author(s).)

Background: Near-infrared fluorescence indocyanine green lymphangiography, a primary modality for detecting lymphedema, which is a disease due to lymphatic obstruction, enables real-time observations of lymphatics and reveals not only the spatial distribution of drainage (static analysis) but also information on the lymphatic contraction (dynamic analysis)., Methods: We have produced total lymphatic obstruction in the upper limbs of 18 Sprague-Dawley rats through the dissection of proximal (brachial and axillary) lymph nodes and 20-Gy radiation (dissection limbs). After the model formation for 1 week, 9 animal models were observed for 6 weeks using near-infrared fluorescence indocyanine green lymphangiography by injecting 6-μL ICG-BSA (indocyanine green-bovine serum albumin) solution of 20-μg/mL concentration. The drainage pattern and leakage of lymph fluid were evaluated and time-domain signals of lymphatic contraction were observed in the distal lymphatic vessels. The obtained signals were converted to frequency-domain spectrums using signal processing., Results: The results of both static and dynamic analyses proved to be effective in accurately identifying the extent of lymphatic disruption in the dissection limbs. The static analysis showed abnormal drainage patterns and increased leakage of lymph fluid to the periphery of the vessels compared with the control (normal) limbs. Meanwhile, the waveforms were changed and the contractile signal frequency increased by 58% in the dynamic analysis. Specifically, our findings revealed that regular lymphatic contractions, observed at a frequency range of 0.08 to 0.13 Hz in the control limbs, were absent in the dissection limbs. The contractile regularity was not fully restored for the follow-up period, indicating a persistent lymphatic obstruction., Conclusions: The dynamic analysis could detect the abnormalities of lymphatic circulation by observing the characteristics of signals, and it provided additional evaluation indicators that cannot be provided by the static analysis. Our findings may be useful for the early detection of the circulation problem as a functional evaluation indicator of the lymphatic system., Competing Interests: Disclosures None.

Despite the tireless efforts of many researchers in lymphatic research, indocyanine green (ICG) solution conditions suitable for lymphatic circulation tests have not been perfectly established yet. We aimed to investigate the optimal in vivo conditions of ICG solution to avoid photobleaching and quenching effects, which may affect the accuracy of lymphatic circulation evaluation. After ICG fluorescence intensity (or ICG intensity) was assessed under different in vitro conditions, the image quality of brachial lymph nodes (LNs) and collecting lymphatic vessels (LVs) in eight rats was investigated. The in vitro results showed that ICG intensity depends on concentration and time in various solvents; however, the brightest intensity was observed at a concentration of 8-30 μg/mL in all solvents. ICG concentration in the albumin (bovine serum albumin; BSA) solution and rat's plasma showed more than two times higher fluorescence intensity than in distilled water (DW) in the same range. However, saline reduced the intensity by almost half compared to DW. In the in vivo experiment, we obtained relatively high-quality images of the LNs and LVs using ICG in the BSA solution. Even at low concentrations, the result in the BSA solution was comparable to those obtained from high-concentration solutions commonly used in conventional circulation tests. This study provides valuable information about the conditions for optimal ICG intensity in near infrared fluorescence indocyanine green (NIRF-ICG) lymphangiography, which may be useful not only for the diagnosis of lymphatic circulation diseases such as lymphedema but also for preclinical research for the lymphatic system., (© 2023. Springer Nature Limited.)

Background  This is a prospective study on 118 patients who underwent lymphaticovenous anastomosis (LVA) due to secondary lower limb lymphedema between January 2018 and October 2020 to evaluate patients' quality of life (QOL) using the Quality of Life Measure for Limb Lymphedema (LYMQoL) questionnaire. Methods  The outcome measurement included the LYMQoL leg scoring system tool evaluating the function, appearance, symptom, mood, and overall outcome. In addition, correlation analysis was performed for three factors: based on International Society of Lymphology (ISL) stages, disease duration, and amount of volume reduction. Results  The LYMQoL tool overall satisfaction score significantly increased at all intervals from 4.4 ± 0.2 preoperative to 6.5 ± 0.3 postoperative at 12 months ( p  < 0.001). Significant findings were seen for each domain scores compared preoperatively and at 12 months: function score (18.6 ± 0.5 to 15.4 ± 0.6), appearance score (17.8 ± 0.5 to 16.0 ± 0.6), symptom score (11.8 ± 0.3 to 8.9 ± 0.4), and mood score (14.5 ± 0.4 to 11.4 ± 0.5; p  < 0.05). The correlation analysis between improvement of the overall score and the ISL stage ( p  = 0.610, correlation coefficient [ r ] = - 0.047), disease duration ( p  = 0.659, r  = - 0.041), and amount of limb volume reduction ( p  = 0.454, r  = - 0.070) showed no statistical significance. Conclusion  The QOL of secondary lower limb lymphedema patients was significantly improved after LVA regardless of the severity of disease, duration of disease, and amount of volume reduction after LVA. Understanding the patient-reported outcome measurement will help the surgeons to manage and guide the expectations of the patients., Competing Interests: Conflict of Interest H.P.S. is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Escin, a naturally derived material isolated from horse chestnut, is used as an anti-inflammatory and anti-edema agent. This study aimed to evaluate its effects on lymphedema in a rat tail model. We divided the rats into five groups. The treatment groups received topical application of escin gel at concentrations of 20%, 10%, 2%, and 0.5% for 4 weeks. The fifth group served as a control. We performed volumetric (water displacement) tests, H&E staining, and LYVE-1 immunohistochemical staining, followed by statistical evaluation. All treatment groups showed significant volumetric reductions compared with the control group, but no significant differences were observed between the treatment groups. H&E staining showed a significant reduction in dermal thickness in the 20%, 10%, and 2% escin treatment groups compared to the control group. Within the treatment groups, the 2% escin group showed a significant difference compared with the 20% and 10% escin groups (p = 0.021 for both). LYVE-1 immunohistochemical staining revealed a significantly higher mean lymphatic vessel count in the 2% escin group compared with the 20%, 10%, and 0.5% escin-treated groups and the control group (p = 0.019, p = 0.025, p = 0.019, and p = 0.032 respectively). Topical escin applied to a rat tail model of acute lymphedema resulted in a significant reduction in tail volume, reduced dermal thickness, and increased lymphatic structures. The 2% escin concentration may be the optimal dose for improving lymphedema in this model. Further research is warranted to explore the clinical application of escin in patients with lymphedema.

Background: The effects of inspiratory muscle training (IMT) with pulmonary rehabilitation (PR) on patients with non-small cell lung cancer (NSCLC) receiving radiotherapy (RT) have not previously been reported. This pilot study aimed to determine the effectiveness of IMT with PR on respiratory muscles and exercise capacity of NSCLC patients receiving RT., Methods: We retrospectively analyzed 20 patients who underwent RT for NSCLC. The rehabilitation included IMT, stretching, strengthening, and aerobic exercises three times a week for 4 weeks with concurrent RT. IMT training lasted 10 min, consisting of one cycle of 30 breaths using the Powerbreathe KH1 device in the hospital by a physical therapist. Patients underwent two IMT sessions at home daily at an intensity of approximately 30%-50% of the participant's maximum inspiratory muscle pressure (MIP) using the threshold IMT tool. We analyzed the results from the respiratory muscle strength test, pulmonary function test, 6-min walk test (6MWT), cardiopulmonary function test, cycle endurance test (CET), Inbody test, grip measurement, knee extensor/flexor strength measurement, Cancer Core Quality of Life Questionnaire (EORTCQ-C30), and NSCLC 13 (EORTC-LC13)., Results: There were no adverse events during evaluation and IMT with PR. MIP (60.1 ± 25.1 vs. 72.5 ± 31.9, p = 0.005), 6MWT (439.2 ± 97.1 vs. 60.7 ± 97.8, p = 0.002), CET (181.39 ± 193.12 vs. 123.6 ± 87.6, p = 0.001), knee extensor (14.4 ± 5.3 vs. 17.4 ± 5, p = 0.012), and knee flexor (14.0 ± 5.2 vs. 16.9 ± 5.5, p = 0.004) significantly improved after IMT with PR., Conclusion: IMT with PR appears effective on respiratory muscles and exercise capacity without adverse events in NSCLC patients who underwent RT., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Cancer-related lymphedema (LE) is often caused by radiotherapy and surgery such as lymph node dissection (LND). Previous studies have reported that exercise is beneficial to relieve LE, but the changes in the lymphatic system following exercise are still unclear. This study aimed to examine the changes in lymphatic drainage pathways over the exercise period and beneficial effects of exercise in rats with LE. Twelve rats were randomly allocated into exercise and control groups (EG and CG; n = 6 each). To obtain LE, inguinal and popliteal LND followed by 20 Gy irradiation was performed. Treadmill exercise was 30 minutes/day, 5 days/week over the four-week period. Consecutive indocyanine green (ICG) lymphography images were collected and classified into five patterns: i) linear; ii) splash; iii) stardust; iv) diffuse, and v) none. Ankle thickness was measured weekly. Histopathological evaluation was performed to examine the skin thickness, collagen area fraction (%) and lymphatic vessel density in harvested tissue. ICG lymphography exhibited more linear and splash patterns in the EG at week 3. The difference of swelling between both groups was significantly different at week 4 (p = 0.016). Histopathologic data revealed a thinner epidermis (p = 0.041) and dermis (p = 0.002), lower collagen area fraction (%, p = 0.002), and higher lymph vessel density (p = 0.002) in the EG than the CG. In conclusion, we found that postoperative exercise can facilitate improvement in lymphatic fluid retention in the lymphedema rat model, resulting in improvement of pathological conditions in the lymphatic system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background:  In lymphedema, lymphatic fluid accumulates in the interstitial space, and localized swelling appears. Lymphovenous anastomosis (LVA) is the most widely used surgery to rebuild a damaged lymphatic system; however, assessing outcome of LVA involves performing volume measurements, which provides limited information on body composition changes. Therefore, we analyzed the bioelectrical impedance analysis (BIA) parameters that can reflect the status of lymphedema patients who underwent LVA., Methods:  We retrospectively reviewed records of 42 patients with unilateral lower extremity lymphedema who had LVA. We measured the perioperative BIA parameters such as extracellular water (ECW) ratio and volume as defined by the percentage of excess volume (PEV). We evaluated the relationship between the amount of change in PEV and in BIA parameters before and after surgery. We confirmed the correlation between ΔPEV and BIA parameters using Spearman's correlation., Results:  Most patients included had secondary lymphedema due to cancer. Average age was 51.76 years and average body mass index was 23.27. PEV and all BIA parameters after surgery showed a significant difference ( p  < 0.01) compared with preoperative measurements. The ECW ratio aff / unaff showed the strongest correlation with PEV with a correlation coefficient of 0.473 ( p  < 0.01)., Conclusion:  Our findings suggest that BIA parameters, especially ECW ratio aff / unaff could reflect the status of patients with lower limb lymphedema after LVA. Appropriate use of BIA parameters may be useful in the postoperative surveillance of patients., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: This study investigated the anatomical and histological characteristics of the rat Eustachian tube (E-tube) and the feasibility of Eustachian tubography in a rat model., Materials and Methods: Fifteen male Wistar rats were used in this study, and the bilateral E-tubes of each rat were examined. Ten E-tubes were used for anatomical studies, another ten for histological analysis, and the other ten for Eustachian tubography. Five rats were euthanized and decapitated, and ten E-tubes were dissected to describe the anatomy of the E-tube. Ten E-tube specimens obtained from five other rats were sectioned to investigate E-tube histology. Eustachian tubography was performed on the bilateral E-tubes of the other five rats using the trans -tympanic approach., Results: The rat E-tubes consisted of bony and membranous parts. Cartilage and bone tissue covered only the bony part. The E-tubes' mean diameter and overall length were 2.97 ​mm and 4.96 ​mm, respectively. The tympanic orifices' mean diameter was 1.21 ​mm. The epithelium of E-tubes was mainly composed of pseudostratified ciliated and goblet cells. Eustachian tubography was successfully performed on both sides of the E-tube for each rat. The technical success rate was 100%, the average running time was 4.9 ​min, and no procedure-related complications occurred. On tubography images, the E-tube, tympanic cavity, and nasopharynx could be identified because of the visualization of bony landmarks., Conclusion: In this study, we described the anatomical and histological features of rat E-tubes. With the aid of these findings, E-tube angiography was successfully performed using a transtympanic approach. These results will facilitate further investigation of E-tube dysfunction., Competing Interests: The authors have declared no conflict of interest., (© 2022 Shanghai Journal of Interventional Radiology Press. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Objective: To determine the effects of multimodal rehabilitation initiated immediately after esophageal cancer surgery on physical recovery compared with conventional pulmonary rehabilitation., Design: Retrospective study., Setting: Private quaternary care hospital., Participants: Fifty-nine inpatients (N=59) who participated in either conventional pulmonary rehabilitation (n=30) or in multimodal rehabilitation (n=29) after esophageal cancer surgery were included., Interventions: Both groups performed pulmonary exercises, including deep breathing, chest expansion, inspiratory muscle training, coughing, and manual vibration. In the conventional pulmonary rehabilitation group, light-intensity mat exercise, stretching, and walking were performed. The multimodal rehabilitation group performed resistance exercises and moderate- to high-intensity aerobic interval exercises using a bicycle., Main Outcome Measures: The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30), pain, 6-minute walk test (6MWT), 30-second chair stand test, and grip strengths were assessed before and after the rehabilitation programs., Results: Symptom scales of pain, dyspnea, and insomnia in the EORTC QLQ-C30 as well as 6MWT improved significantly after each program (P<.05). 6MWT (73.1±52.6 vs 28.4±14.3, P<.001, d=1.15), 30-second chair stand test (3.5±3.9 vs 0.35±2.0, P<.001, d=1.06), and left grip strength (1.2±1.3 vs 0.0±1.5, P=.002, d=0.42) improved significantly in the multimodal rehabilitation group compared with the pulmonary rehabilitation group. While right grip strength also showed more improvement for those undergoing the multimodal program, the mean strength difference was not clinically meaningful., Conclusions: A multimodal inpatient rehabilitation program instituted early after esophageal cancer surgery improved endurance for walking more than conventional pulmonary rehabilitation as measured by the 6MWT and the 30-second chair stand test., (Copyright © 2022. Published by Elsevier Inc.)

Background: Constructing a reliable animal model for preclinical treatment of secondary lymphedema is challenging because the anatomical characteristics near the lymph nodes are understudied. Therefore, this study examined the detailed anatomical relationship between the axillary lymph node flaps (ALNFs) and brachial lymph node flaps (BLNFs) in the forelimb of Sprague-Dawley (SD) rats., Materials and Methods: Ten male rats, weighing 250-300 g, were used. The ALNFs and BLNFs on either side of the rat forelimbs were dissected. The two lymph node flaps (LNFs) were immediately harvested to analyze their physical characteristics (via imaging process software) and microscopic structure (via histology examinations)., Results: A total of 20 ALNFs and BLNFs from 10 rats were harvested and analyzed. ALNF dissection was simpler and lasted a shorter time than BLNF dissection ( p < 0.0001). The left LNFs were more difficult to dissect than the right LNFs ( p < 0.0001). In physical characteristics of LNFs, the area ( p < 0.001) of LNFs and the number of lymph nodes ( p < 0.0001) associated with ALNFs were greater than those associated with BLNFs, but the pedicle lengths of ALNFs were shorter than that of BLNFs ( p < 0.0001). No significant difference in the diameter of the venous and arterial pedicles was noted between the two LNFs ( p > 0.05)., Conclusion: This study reported detailed physical characteristics of ALNFs and BLNFs in SD rat forelimbs, assessing the respective area of LNFs, number of lymph nodes, and lengths and diameters of vascular pedicles. Moreover, this study suggested an efficient method to perform a study of LNFs by describing the operation process and repeatedly measuring the operation time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Yang, Kim, Gelvosa, Wei, Jeon and Cheon.)

Purpose of Review: This review aimed to increase the understanding of oncologists and physiatrists about the necessity, efficacy, and safety of rehabilitation in advanced cancer patients with bone metastases and neural compromise., Recent Findings: Recently, there are growing evidence supporting the safety and efficacy of rehabilitation in patients with bone metastases and neural compromise. Despite the potential benefits of rehabilitation, however, rehabilitative services are considerably underutilized in clinical practice. Many oncologists are not familiar with functional issues and have limited understanding of the available rehabilitative services. Moreover, medical professionals, even physiatrists, have uncertainties and concerns about skeletal complications and often regard rehabilitation as a contraindication in this patient group. This review aimed to raise awareness on the role of rehabilitation in the continuum of cancer treatment, to improve its use in clinical practice. A multidisciplinary team approach involving physiatrist may facilitate integration of relevant clinicians., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Secondary lymphedema is a severe complication of cancer treatment, but there is no effective curative method yet. Lymph node dissection and radiation therapy for cancer treatment may lead to secondary lymphedema, which is a chronic disease induced by malfunction of lymphatic flow. The lymphatic channel sheet (LCS) is an artificial micro-fluidic structure that was fabricated with polydimethylsiloxane to maintain lymphatic flow and induce lymphangiogenesis. The structure has two-dimensional multichannels that increase the probability of lymphangiogenesis and allow for relatively easy application. We verified the efficacy of the lymphatic channel sheet through macroscopic and microscopic observation in small animal models, which underwent brachial lymph node dissection and irradiation. The lymphatic channel sheet enabled the successful transport of lymphatic fluid from the distal to the proximal area in place of the removed brachial lymph nodes. It prevented swelling and abnormal lymphatic drainage during the follow-up period. Lymphangiogenesis was also identified inside the channel by histological analysis after 8 weeks. According to these experimental results, we attest to the roles of the lymphatic channel sheet as a lymphatic pathway and scaffold in the rat upper limb model of secondary lymphedema. The lymphatic channel sheet maintained lymphatic flow after lymph node dissection and irradiation in an environment where lymph flow is cut off. It also relieved symptoms of secondary lymphedema by providing a lymph-friendly space and inducing lymphangiogenesis., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers.)

The self-expanding metal stent (SEMS) is a versatile, palliative treatment method for unresectable, malignant, non-vascular strictures. Colorectal cancer (CRC) is one of the candidates for the application of the SEMS, in combination with the photothermal ablation (PTA) technique that enhances its therapeutic efficacy. The objective of this study was to investigate the efficacy of stent-mediated PTA therapy in an endoscopy-guided, orthotopic rectal cancer model. A total of 30 of 40 mice with the tumor size of grade 4 were included and were divided into three groups of 10 mice each. Group A underwent a gold nanoparticle (AuNP)-coated SEMS but no near-infrared (NIR) irradiation, group B received an uncoated control SEMS with NIR irradiation, and group C received a AuNP-coated SEMS and NIR irradiation together. Colonoscopy and in vivo imaging, immunohistochemical analysis, and quantitative reverse-transcription polymerase chain reaction of major tumor markers were performed. Stent placement and PTA were technically successful using colonoscopy. The tumor grade reduction after PTA is significant in group C, compared with groups A or B ( p < 0.001). Molecular analysis validated this observation with a significantly reduced Mapk1 proliferation marker or increased Jnk expression. Histological analysis confirmed the localized PTA therapy using AuNP-coated SEMS profoundly ablated tumor outgrowth through the stent. Our results indicate that this novel strategy of localized PTA therapy could be a promising option for palliative treatment of CRC and to support prolonged stent patency with a decreased tumor volume.

Purpose: Data are lacking regarding pulmonary rehabilitation (PR) programs in patients with lung cancer receiving radiation therapy. This study aimed to confirm the feasibility of an outpatient-based PR program in lung cancer patients during radiation therapy., Methods: A retrospective chart review was performed of 40 patients with lung cancer who had undergone radiation therapy between July and December 2019. The patients received an outpatient-based PR program for a total of eight sessions two times weekly comprising 60 min per session. Feasibility was assessed based on the completion rate, adverse events, and satisfaction with the PR program. Functional evaluations using 6-min walk and grip strength tests were conducted before and after PR. Patient quality of life was assessed by the EORTC QLQ-C30 questionnaire before and after PR., Results: The completion rate for the PR program was 72.5% among the 40 patients. No adverse events related to PR were reported. The overall satisfaction was 5.7 ± 1.1 on a seven-point Likert scale in all participants. The mean 6-min walk test distance increased significantly from 419.1 to 446.2 m. The improvement in grip strength in the dominant hand after PR was not significant. The social functioning score in the EORTC QLQ-C30 improved significantly., Conclusion: The results of this study showed the feasibility without serious adverse effects of a 4-week outpatient-based PR program for lung cancer patients undergoing outpatient-based radiation therapy. This program might improve patient physical function and quality of life., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Purpose: To investigate the characteristics of lymphedema in patients treated with mammalian target of rapamycin (mTOR) inhibitors and delineate complex decongestive therapy (CDT) outcomes. Methods and Results: We retrospectively analyzed 24 patients with mTOR inhibitor-induced lymphedema and 7 lymphedema patients (control) not treated with mTOR inhibitors, who visited the lymphedema clinic of the department of rehabilitation medicine from March 2016 to December 2019. We comprehensively reviewed clinical features, medication history, associated diseases, lymphoscintigraphy, lower extremity computed tomography venography (LE CTV), and the effect of CDT. By using ImageJ program, we measured the cross-sectional area (CSA) of muscle and subcutaneous fat of mid-thigh image in LE CTV and compared them to a control group not treated with mTOR inhibitors. Seventeen patients on sirolimus and seven patients on everolimus were included, with an approximately equal distribution of stages 2 and 3 lymphedema, and most with pitting edema. Ten patients had breast or gynecological cancer and underwent lymph node dissection. Lymphedema developed after mTOR inhibitor initiation, not postoperatively. Lymphoscintigraphy revealed decreased lymph node uptake and dermal backflow. LE CTV revealed subcutaneous honeycomb-shaped trabecular areas in the affected limbs of seven patients. Patients treated with mTOR inhibitors had a larger mean subcutaneous fat CSA and a smaller mean muscular CSA than controls. Lymphedema improved or remained unchanged after initial CDT. Daily CDT adequately controlled 11 cases, but exacerbation occurred in 5 of 7 poorly compliant patients, and cellulitis occurred in 6 patients. Conclusion: Physicians should identify mTOR inhibitor-related lymphedema early and discuss medication alternatives and CDT with patients.

Background: The pediatric lung transplant is a very important treatment for patients with end-stage lung diseae, and pulmonary rehabilitation (PR) is also an important factor in determining the prognosis. However, there is no much literature available on pulmonary rehabilitation in pediatric patients' post lung transplant. Through this case report, we would like to present our intensive PR program for pediatric patients' post-lung transplant., Patient Concerns: The 10-year-old boy's breathing before receiving a lung transplant continued to deteriorate and he eventually became dependent on a wheelchair., Diagnosis: He was diagnosed with infantile acute lymphoblastic leukemia at 6 months of age. At the age of one year, he underwent allogeneic bone marrow transplantation, but was diagnosed with post-transplantation bronchiolitis obliterans (PTBO) two months later. He had a lung transplant at the age of 10., Interventions: He was hospitalized and received an initial assessment. This assessment included functional, cognitive, and psychological evaluations. He additionally completed PR exercises twice daily for two weeks. After discharge, he continued to participate in an outpatient-based PR program for three months. During the outpatient phase, PR exercises were performed once weekly, in addition to home-based cognitive training., Outcomes: Our intensive post-lung PR program improved our patient's exercise capacity, lung function, and quality of life. As a comprehensive rehabilitation service, our program also included a cognitive training component., Conclusion: We describe an intensive PR program tailored to pediatric patients' post-lung transplant. The program was feasible and resulted in improvements in functional exercise capacity, lung function, and quality of life. Future research into our method is necessary for continued improvement of this novel program., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Traditionally, lymphovenous anastomosis is not routinely performed in patients with advanced stage lymphedema because of difficulty with identifying functioning lymphatics. This study presents the use of duplex ultrasound and magnetic resonance lymphangiography to identify functional lymphatics and reports the clinical outcome of lymphovenous anastomosis in advanced stage lower extremity lymphedema patients., Methods: This was a retrospective study of 42 patients (50 lower limbs) with advanced lymphedema (late stage 2 or 3) that underwent functional lymphovenous anastomoses. Functional lymphatic vessels were identified preoperatively using magnetic resonance lymphangiography and duplex ultrasound., Results: An average of 4.64 lymphovenous anastomoses were performed per limb using the lymphatics located in the deep fat underneath the superficial fascia. The average diameter of lymphatic vessels was 0.61 mm (range, 0.35 to 1 mm). The average limb volume was reduced 14.0 percent postoperatively, followed by 15.2 percent after 3 months, and 15.5 percent after 6 months and 1 year (p < 0.001). For patients with unilateral lymphedema, 32.4 percent had less than 10 percent volume excess compared to the contralateral side postoperatively, whereas 20.5 percent had more than 20 percent volume excess. The incidence of cellulitis decreased from 0.84 per year to 0.07 per year after surgery (p < 0.001)., Conclusion: This study shows that functioning lymphatic vessels can be identified preoperatively using ultrasound and magnetic resonance lymphangiography; thus, lymphovenous anastomoses can effectively reduce the volume of the limb and improve subjective symptoms in patients with advanced stage lymphedema of the lower extremity., Clinical Question/level of Evidence: Therapeutic, IV., Competing Interests: Disclosure:The authors of this article do not have any conflict of interest to declare in relation to its content., (Copyright © 2020 by the American Society of Plastic Surgeons.)

Background: When a patient with breast cancer-related lymphedema (BCRL) depends on continuous compression management, that is, when interstitial fluid accumulation is continuously ongoing, surgical treatment should be considered. Physiologic surgery is considered more effective for early-stage lymphedema. The purpose of this study was to identify predictors of patients with BCRL who will be compression-dependent despite 2 years of conservative care., Methods: This study included patients with BCRL who followed up for 2 years. Patients were classified into two groups (compression-dependent vs. compression-free). We identified the proportion of compression-dependent patients and predictors of compression dependence., Results: Among 208 patients, 125 (60.1%) were classified into the compression-dependent group. Compression dependence was higher in patients with direct radiotherapy to the lymph nodes (LNs), those with five or more LNs resections, and those with BCRL occurring at least 1 year after surgery., Conclusions: BCRL patients with direct radiotherapy to the LNs, extensive LN dissection, and delayed onset may be compression-dependent despite 2 years of conservative care. Initially moderate to severe BCRL and a history of cellulitis also seem to be strongly associated with compression dependence. Our results allow for the early prediction of compression-dependent patients who should be considered for physiologic surgery.

Background and Aims: Minimally invasive therapies for obesity are a bridge between lifestyle interventions and bariatric surgery. We developed a novel device to reduce weight gain rate and evaluated its safety and efficacy in juvenile pigs., Methods: The intragastric satiety-inducing device (ISD) comprises a self-expandable esophageal metal stent connected to a star-shaped disc placed in the stomach fundus. Eight juvenile pigs were randomized into ISD (n = 5) and control (n = 3) groups. Body weight and serum ghrelin hormone were monitored weekly for 6 weeks. One pig was followed up for 4 additional weeks (rebound pig) after ISD removal. Histological examination and immunohistochemistry for the interstitial cells of Cajal (ICCs) were performed., Results: ISD placement was successful in all pigs. Two ISDs (40%) migrated at 4 and 5 weeks after placement. Weight gain rates were significantly lower in the ISD group than in the control group from week 1 to 6 but were higher in the rebound pig than in a control pig from week 7 to 10. Mean ghrelin hormone level was higher in the control group than in the ISD group from week 1 to 6. ISD induced reversible inflammatory changes in the esophagus and stomach fundus. The number of ICCs was lesser in ISD pigs than in control and rebound pigs., Conclusions: ISD placement is feasible and safe in juvenile pigs. It decreases weight gain rate but induces reversible inflammatory reaction and tissue hyperplasia. Its mechanism may be related to pressure exertion on the stomach fundus or gastric motility alteration.

Background: Acquired lymphedema is a common consequence of cancer surgery. Fibrosis is one of the main causes of chronic lymphedema since it hinders lymphatic regeneration and this causes a significant decrease in lymphatic flow and accumulation of excessive protein-rich fluid. The transforming growth factor-β1 (TGF-β1) signaling pathway is known in a process of wound repair and fibrosis. In our study, the purpose was to evaluate the efficacy of EW-7197, a peroral TGF-β type I receptor kinase inhibitor, in treating acquired lymphedema. Methods and Results: For lymphedema mouse tail model, we used 10- to 12-week-old female C57BL/6 mice. The skin was circumferentially excised, making a circular band followed by cauterization of lymphatic collecting vessels. Two groups were made in this study: control and treatment. The treatment group ( n  = 12) received a solution consisting of 0.1 mL of artificial gastric juice and 20 mg/kg EW-7197 by gavage once daily. For evaluation, tail diameter measurement, fluorescence lymphography, and immunofluorescence images were used. EW-7197 treatment ameliorates acquired lymphedema in a mouse tail model by increasing lymphangiogenesis and interstitial flow of the lymphatics by inhibition of the fibrosis. The differences in maximal tail thicknesses between the control and treatment groups were statistically significant from 2 to 4 weeks after surgery. The treatment group showed a greater number of lymphatic vessels at the surgery site than the control group. The treatment group also showed more FITC coverage area at the surgery site. Conclusion: EW-7197 treatment ameliorates acquired lymphedema in a mouse tail model by increasing lymphangiogenesis and interstitial flow.

Background: To evaluate the usefulness of quantitative findings of pretherapy lymphoscintigraphy in predicting the effects of complex decongestive therapy (CDT) in patients with upper extremity lymphedema after breast cancer treatment. Methods and Results: We retrospectively analyzed patients with unilateral breast cancer-related lymphedema (BCRL) who underwent pretherapy lymphoscintigraphy and completed 2 weeks of CDT. A total of 18 patients with unilateral BCRL clinical stage II underwent 30-minute sessions of CDT five times per week for 2 weeks. The quantitative asymmetry index (QAI) of the upper extremity, axillary lymph node (LN) uptake, and axillary plus supraclavicular LN uptake from lymphoscintigraphy were calculated. The volume of lymphedema was calculated by percentage excess volume (PEV) at initial and posttreatment. The CDT response was assessed using percentage reduction in excess volume (PREV). Correlation analyses were conducted using Kendall tau rank correlation. There was positive correlation between upper extremity QAI at 2 hours and initial PEV. Negative correlations were found between axillary LN QAI at 1, 2 hours, and initial PEV, and between axillary plus supraclavicular LN QAI at 1, 2 hours, and initial PEV. The PREV showed a positive correlation with axillary LN QAI at 2 hours after injection (tau-b = 0.354, p  = 0.041). Conclusion: Quantitative findings of pretherapy lymphoscintigraphy have potential value for use in predicting the response to CDT in patients with upper extremity lymphedema after breast cancer treatment. Using QAIs from lymphoscintigraphy, we could estimate the excess volume of lymphedema.

Purpose: Restricted shoulder mobility is a major upper extremity dysfunction associated with lower quality of life and disability after breast cancer surgery. We hypothesized that a poloxamer and sodium alginate mixture (Guardix-SG®) applied after axillary lymph node dissection (ALND) would significantly improve shoulder range of motion (ROM) in patients with breast cancer., Methods: We conducted a double-blind, randomized, prospective study to evaluate the clinical efficacy and safety of Guardix-SG® for the prevention of upper extremity dysfunction after ALND. The primary outcome measure was shoulder ROM at baseline (T0) and 3 (T1), 6 (T2), and 12 months (T3) after surgery. Secondary outcome measures were the Disabilities of the Arm, Shoulder, and Hand score(DASH), pain associated with movement, which was assessed using a numeric rating scale, and lymphedema assessed using body composition analyzer., Results: A total of 83 women with breast cancer were randomly assigned to either the Guardix-SG® group or the control group. In the Guardix-SG® group (n = 37), Guardix-SG® was applied to the axillary region after ALND. In the control group (n = 46), ALND was performed without using Guardix-SG®. Comparing ROM for shoulder flexion before surgery (178.2°) and 12 months after surgery (172.3°), that was restored 12 months after surgery in the Guardix-SG® group, and there was no statistically significant difference between that at before surgery and 12 months after surgery (p = 0.182). No adverse effect was observed in either group., Conclusions: The results of this study have shown that Guardix-SG® help improve shoulder ROM without causing adverse effects in patients who underwent breast cancer surgery. However, there was no statistically significant difference from the control group. A further large-scale study is needed to obtain a more conclusive conclusion., Trial Registration: CRISKCT0003386; https://cris.nih.go.kr (20181207)., Competing Interests: The grants from Hanmi Pharmaceutical Co., Ltd., Seoul, Korea, covered the cost for the Guardix- SG® syringes used in this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no new patents or products in development associated with this research to declare.

Lower extremity (LEx) edema is a common complication in gynecologic cancer patients. There are 2 main causes of edema in these patients such as deep vein thrombosis (DVT) and lymphedema. Early diagnosis and treatment of DVT are certainly important, but it is often difficult to evaluate proximal DVT by using ultrasound. The aim of this study is to demonstrate the usefulness of computed tomography venography of the lower extremity (CTV LEx) for the diagnosis of the DVT and investigate predictive factor of DVT in gynecologic cancer patients with LEx edema.The medical records of 415 gynecologic cancer patients who were referred to the department of rehabilitation medicine with LEx edema were retrospectively reviewed in this case-controlled study. We categorized CTV LEx findings as follows: DVT proximal to the inguinal ligament (inferior vena cava or iliac vein thrombosis) and DVT distal to the inguinal ligament (femoral, popliteal, or calf vein thrombosis). We also evaluated patient characteristics including D-dimer level. We analyzed the correlation of each factor with DVT frequency and used receiver operating characteristic curve analysis to determine the appropriate D-dimer threshold.Sixty-six patients were diagnosed with DVT; of them, 35 (53%) had DVT proximal to the inguinal ligament. Twenty-two patients were diagnosed with pulmonary embolism, of whom 15 had proximal DVT. Patients with proximal DVT tended to have pulmonary embolism (P < .001). Distal organ metastasis (odds ratio [OR], 2.88; P = .002) and a high D-dimer level (OR, 1.13; P = .001) were correlated with DVT.CTV LEx is a useful diagnostic tool for gynecologic cancer patients with LEx edema, particularly high-risk patients, that should be performed at the initial evaluation.

Objective: To determine whether the bioimpedance analysis (BIA) ratios of upper to lower extremities could predict treatment outcomes after complex decongestive therapy (CDT) for gynecological cancer related lymphedema (GCRL)., Methods: A retrospective study, from March 2015 to December 2018, was conducted. The study sample comprised patients receiving CDT, 30 minutes per day, for 10 days. Bioimpedance was measured pre- and post-CDT. Circumference measurements were obtained at 20 and 10 cm above the knee (AK) and 10 cm below the knee (BK). We calculated the expected impedance at 0 Hz (R0) of extremities and upper/lower extremity R0 ratios (R0U/L). We evaluated the relationship between R0U/L and changes in R0U/L and circumferences, pre- and post-CDT., Results: Overall, 59 patients were included in this study. Thirty-one lower extremities in 26 patients comprised the acute group, and 38 lower extremities in 33 patients comprised the chronic group. Pre-treatment R0U/L was significantly correlated with R0U/L change after adjusting for age and BMI (acute: R=0.513, p<0.01; chronic: R=0.423, p<0.01). In the acute group, pre-treatment R0U/L showed a tendency to be correlated with circumference change (AK 20 cm: R=0.427, p=0.02; AK 10 cm: R=0.399, p=0.03)., Conclusion: Our study results suggested that pre-treatment BIA could predict volume reductions after CDT in the early stages of GCRL. These findings implied that BIA value could be one possible parameter to apply in treatment outcomes prediction, during the early stage of GCRL. Therefore, further large-scale prospective studies will be beneficial.

Despite the promising results from the placement of covered or uncovered self-expandable metallic stent (SEMS) as a nonsurgical therapeutic option for the malignant gastric outlet obstruction (GOO), the long patency of the stent is still limited because of stent-induced tissue hyperplasia. Here, a local heat treatment using a nanofunctionalized SEMS is proposed for suppressing stent-induced tissue hyperplasia during GOO treatment. Highly efficient photothermal gold nanoparticle (GNP) transducer-coated SEMSs (GNP-SEMSs) were prepared for local heat treatment in rat gastric outlet. The in vivo heating temperature in rat gastric outlet model was evaluated and compared with in vitro heating temperature. Three groups of our developed 45 rat gastric outlet models were used: group A, noncoated SEMS only; group B, GNP-SEMS plus local heating; and group C, GNP-SEMS only to investigate in vivo efficacy of GNP-SEMS mediated local heating. Ten rats per group were sacrificed for 4 weeks, and five rats per group were sacrificed immediately after local heat treatment. The in vivo heating temperature was found to be 10.8% lower than the in vitro heating temperatures. GNP-SEMSs were successfully placed through a percutaneous approach into the rat gastric outlet ( n = 45). The therapeutic effects of GNP-SEMS were assessed by histologic examination including hematoxylin-eosin, Masson trichrome, immunohistochemistry (TUNEL and CD31), and immunofluorescence (Ki67), and the results showed significant prevention of tissue hyperplasia following stent placement without adjacent gastrointestinal tissue damage. GNP-SEMS-mediated local heating could be an alternative therapeutic option for the suppression of tissue hyperplasia following stent placement in benign and malignant GOOs.

Purpose: Brachial plexopathy in cancer patients is a rare but significant complication that causes pain and disability of the upper extremities. Clinical features of breast cancer patients with metastatic brachial plexopathy (MBP) have not been studied. We aimed to investigate the characteristics of MBP in breast cancer patients., Methods: We retrospectively reviewed medical records of patients with breast cancer with MBP who visited Asan Medical Center from 2000 to 2016; we enrolled 44 patients. We comprehensively reviewed the characteristics, range of metastatic lymph nodes, initial symptoms, location, and severity of brachial plexus injury by electrodiagnostic study, radiologic findings, and associated complications., Results: The mean age of patients with MBP was 51.9 ± 9.3 years; 25% were diagnosed with stage IV breast cancer at initial diagnosis. Weakness was the most common initial symptom of MBP (52.3%). Most patients showed limitation of shoulder range of motion and pain; 66% of patients exhibited malignant lymphedema. Forty-one patients were evaluated by electromyography; upper nerve trunk involvement (22.0%) was more frequent than lower nerve trunk involvement (9.8%). Nineteen patients underwent brachial plexus MRI, and supraclavicular area (SCA) metastasis was most frequent (57.9%). Sixteen patients were examined by both brachial plexus MRI and electromyography; patients with SCA metastasis exhibited significantly more frequent malignant lymphedema (p = 0.019) and upper nerve trunk involvement (p = 0.035), compared with patients with non-SCA metastasis., Conclusions: Our study revealed clinical features of MBP in breast cancer patients. Additional diagnostic evaluation focused on metastasis or aggravated metastatic tumor is needed when breast cancer patients are diagnosed with brachial plexopathy.

Background: Radiation therapy has been applied to prolong the duration of lymphedema. This study aimed to evaluate the effect of radiation on the development of lymphedema in a mouse hindlimb model. Methods and Results: A total of 24 Balb/c mice underwent the right popliteal lymph node excision and the afferent and efferent lymphatics blockage. The radiation group ( n  = 12) received a single 20 Gy radiation 1 day before surgery in the right hindlimb of each mouse, whereas the control group ( n  = 12) only received surgery without radiation. The right hindpaw thickness of each mouse was measured twice a week for 4 weeks. Fluorescence microscopy images using fluorescein isothiocyanate-dextran tracer were obtained once weekly. Immunohistochemical (IHC) staining images using anti-lymphatic vessel endothelial hyaluronan receptor-1 (anti-LYVE-1) were obtained at 4 weeks after surgery. The radiation group showed significant increase in the thickness of the right hind paws from 0.5 to 2 weeks compared with the control group. As for fluorescence lymphography, the radiation group showed a lower number of regenerated lymphatics and more congestion of tracers in the operated limb at the surgery sites at 1, 2, 3, and 4 weeks after surgery. For the IHC analysis, the radiation group showed a lower number of regenerated lymphatics per high-power field at the surgery site than the control group. Conclusion: Radiation therapy transiently aggravated the extent of lymphedema by inhibiting regenerated lymphatics in a mouse hindlimb model. However, it did not prolong the duration of lymphedema because the cutaneous interstitial flow contributes to the lymphatic fluid clearance.

Purpose: To investigate the effect of prior chemotherapy on self-expanding metal stent (SEMS)-related complications in patients with locally advanced primary esophageal cancer., Materials and Methods: Data from patients with locally advanced primary esophageal cancer who received SEMS placement with or without prior chemotherapy were retrospectively reviewed. Patients were grouped according to prior palliative therapy: group A (n = 41) had received SEMS only, and group B (n = 64) had received palliative chemotherapy prior to SEMS placement. Patients' age, stricture length, tumor location, and dysphagia score prior to SEMS placement were evaluated. The overall patient cohort had a median follow-up period of 129 days (range 11-463). Outcomes after SEMS placement, including technical and clinical success rates, the occurrence of complications, and overall survival, were compared., Results: There were no significant differences between the two groups regarding patients' age, stricture length, tumor location, and dysphagia score prior to SEMS placement. SEMS placement was technically successful in all patients, with no procedure-related complications reported. Clinical success was achieved in 95.1% of patients in group A and 96.8% of patients in group B. The duration of stent patency was significantly shorter in group B [162 days; 95% confidence interval (CI) 126.6-198.4 vs. group A (339 days; 95% CI 258.8-419.3], p = 0.001. No significant differences were seen between the two groups regarding dysphagia score improvement [group A (3.15 ± 0.57 to 1.17 ± 0.83; p < 0.001) and group B (3.17 ± 0.80 to 1.14 ± 0.79; p < 0.001); p = 0.66], complications [group A (10/41), and group B (24/64); p = 0.094], or overall survival [the median and mean overall survival periods were 105 (95% CI 30-180) and 132 days (95% CI 97-167), respectively, in group A, and 126 (95% CI 88-164) and 156 days (95% CI 132-180), respectively, in group B; p = 0.592]., Conclusion: Prior chemotherapy did not increase the risk of complications following SEMS placement in patients with locally advanced esophageal cancer. SEMS patency was significantly longer in patients who did not receive chemotherapy prior to SEMS placement., Level of Evidence: Level 4, Case Series.

Stricture of pancreatic-enteric anastomoses is a major late complication of a pancreaticoduodenectomy for the treatment of a periampullary tumor and can lead to exocrine and endocrine insufficiency such as malnutrition and diabetes mellitus. We investigated the safety and efficacy of a biodegradable tubular stent (BTS) for preventing a pancreaticojejunostomy (PJ) anastomotic stricture in both a rat and porcine model. The BTS was manufactured using a terpolymer comprising poly p-dioxanone, trimethylene carbonate, and glycolide. A cohort of 42 rats was randomized into 7 groups of 6 animals each after BTS placement into the duodenum for the biodegradation assay. A total of 12 pigs were randomized equally into a control and BTS placement group. The effectiveness of the BTS was assessed by comparing radiologic images with histologic results. Surgical procedures and/or BTS placements were technically successful in all animals. The median mass losses of the removed BTS samples from the rat duodenum were 2.1, 6.8, 11.2, 19.4, 26.1, and 56.8% at 1, 2, 3, 4, 6, and 8 weeks, respectively. The BTS had completely degraded at 12 weeks in the rats. In the porcine PJ model, the mean luminal diameter and area of the pancreatic duct in the control group was significantly larger than in the BTS group (all p < 0.05). BTS placement thus appears to be safe and effective procedure for the prevention of PJ anastomotic stricture. These devices have the potential to be used as a temporary stent placement to treat pancreatic-enteric anastomoses, but further investigations are required for optimization in human.

This study was to develop tablet personal computer-based cognitive training programs for children with developmental disabilities whose cognitive age is less than 4 years. Twelve cognitive training programs (named Injini) were designed comprising cognitive domains that included attention, visual and auditory perception, memory, executive function, language, and reasoning. In addition, programs related to learning experiences, such as self-regulation, role play, learning of number, and letter/shape concepts, comparison, classification, and pattern matching, were included. Six of 12 programs comprised approximately 10 levels for each program, with different difficulty levels. Other programs consisted of universal tasks that did not have a difficulty level. To ensure that the difficulty level was appropriate, we pre-tested the pilot version of Injini among 80 children with typical development aged 18 to 41 months. After modifying the pilot version, we developed the final version and tested it among 80 children with cognitive impairment whose cognitive age was 18 to 41 months. All children were assessed using the Bayley Scales of Infant and Toddler Development to determine their development and cognitive age. The difficulty level analyses in children with typical development revealed several inappropriate results wherein the success rate did not decrease with increase in level in some programs. After adjusting the difficulty level, the analyses in children with cognitive impairment demonstrated that the success rate gradually decreased with increasing level in all programs. Cognitive training programs for children with developmental disabilities were successfully developed.

Purpose: To prospectively evaluate the midterm outcomes of fluoroscopic eustachian tube (E-tube) balloon dilation by using a flexible guide wire in patients with obstructive E-tube dysfunction., Materials and Methods: From October 2016 to September 2017, adult outpatients with persistent otitis media who were unable to perform the Valsalva maneuver were prospectively enrolled. The analysis included 32 E-tubes from 31 patients (18 women, 13 men; mean age, 47 years old, range 25-72 years). Participants underwent fluoroscopic E-tube balloon dilation with a 0.035-inch flexible guide wire and a 6- × 20-mm balloon catheter. Clinical examinations to check for the ability to perform the Valsalva maneuver and otomicroscopy were conducted at 1 week and then at 1, 3, 12, and 18 months after the procedure., Results: Balloon dilation was technically successful in all E-tubes. The mean time required for the procedure was 6.9 minutes (range, 5.8-10.3 minutes). The Valsalva maneuver was successful in opening 25 of 32 E-tubes (78.1%) at 3 months after balloon dilation. During the median follow-up of 15.9 months, failure of the Valsalva maneuver occurred in 4 of 25 improved E-tubes (16%), yielding a 2-year patency rate of 84%., Conclusions: The fluoroscopic balloon dilation results were encouraging, and using a flexible guide wire for E-tube balloon dilation did not cause a false passage., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the clinical outcomes of fully covered self-expanding metal stent (FCSEMS) placement in patients with malignant esophageal obstruction who survived longer than 6 months., Methods: From January 2002 to January 2018, 88 FCSEMS were placed in 64 patients (mean age 62.9 ± 11.6 years; 58 males) with inoperable malignant esophageal obstruction with or without esophago-respiratory fistula. Only patients who survived more than 6 months with FCSEMS in place were included. Data regarding technical and clinical success, complications, reinterventions, stent patency, and patient survival were obtained from a prospectively maintained hospital database., Results: The technical and clinical success rates were 100 % (64/64). During follow-up, the median dysphagia score significantly improved (3.09 ± 0.68 to 1.05 ± 0.60, p < 0.001). The complication rate was 48.8 %. Multivariate analysis revealed that only longer stenting duration was associated with complications [hazard ratio = 1.220, 95 % confidence interval (CI) (1.074-2.760), p = 0.039]. The median follow-up duration was 257 days (range, 181-969). The median stent patency duration was 289 days [95% CI (209.9-368.1)]. The median survival was 254 days [95% CI (219.7-288.3)]., Conclusions: Our data suggest that esophageal FCSEMS placement is an effective option for patients with malignant dysphagia when survival longer than 6 months is expected. The rate of complications increases with time, and SEMS development is needed to keep up with the advancement in oncological treatment., Advances in Knowledge: Fully covered esophageal self-expandable stent placement is effective in patients surviving more than 6 months, however, the rate of complications also increases. SEMS development is needed to cope with the advancement in oncological treatment.

Backgrounds: Secondary lymphedema is a common complication of parasitization and breast or gynecologic cancer therapy; however, options for the treatment of lymphedema are ineffective and limited. A mouse tail model is one of the most successful animal models for a lymphatic study. Lymphedema of the mouse tail is characterized by increases in the volume of the extremity caused by accumulation of tissue fluid, proliferation of fibroblasts and adipocytes, and excessive production of collagen. However, the study of lymphedema using mouse has been plagued with difficulty in directly assessing physiologic changes owing to limitations in the measurement of the mouse tail volume. Furthermore, the mouse tail volume cannot be obtained using the general in vivo measurement method such as volumetric water displacement. Methods and Results: Lymphatic researchers have used the truncated cone formula to approximate the volume as used in the numerical approximation of a cylindrical figure. Although this formula is simple and easy to use, it has difficulties of repeatability and accuracy because the measurement procedure is highly subjective and the accuracy depends on the number of divided segments on the tail. In this article, two novel volumetric measurement methods for the mouse tail model were introduced. The methods were evaluated and compared using three mice with surgically created lymphedema on the tails. Conclusions: The two continuous measuring methods showed a possibility to improve the conventional method by continuous measurement using visual and physical detecting methods. The proposed methods facilitate the extraction of longitudinal section-specific information, which can be an important clue in a lymphatic study.

Purpose: To evaluate the technical feasibility, safety, and efficacy of a novel full sense device (FSD) for the treatment of obesity in a porcine model., Materials and Methods: The novel FSD comprised a self-expanding metallic esophageal stent connected to a star-shaped nitinol disk. Three types of FSD were used: fully covered (type A), fully covered with barbs (type B), and uncovered with barbs (type C). Nine juvenile pigs were divided into two groups: FSD (n = 6) and control (n = 3). FSD type A was placed in the FSD group. In case of migration, either FSD type B or type C was then randomly placed. Food intake was monitored daily. Weight changes and ghrelin hormone levels were monitored weekly for 12 weeks., Results: FSD placement was technically successful in all pigs. All FSDs except one migrated to the stomach within 1 week after placement. The pig in which the FSD was retained showed decreased food intake in the first week after FSD placement, and there was a difference in the final weight between the FSD pig and control pigs. The percentage of weight gain was 116.6% in the control group and 105.3% in the FSD pig., Conclusion: FSD placement under fluoroscopic and endoscopic guidance is technically feasible and safe in a porcine model. The uncovered FSD appears to decrease food intake and reduce the rate of weight gain. However, the high FSD migration rate is not encouraging.

Secondary lymphedema is a chronic debilitating lifelong complication and early diagnosis is crucial. The Inbody 720, which is widely used, has no universal index of diagnostic criteria for test results. We aim to determine the normal range, cutoff values, and mean + standard deviation values of extracellular fluid (ECF) and the single frequency bioimpedance (SFBIA) ratios for the diagnosis of lymphedema and suggest the usefulness of these values for detecting lymphedema.Seventy patients with unilateral breast cancer-related lymphedema and 643 healthy subjects were enrolled. All patients with breast cancer underwent surgeries with dissection of lymph nodes. We analyzed the ECF volume, SFBIA at 1- and 5-kHz frequencies using Inbody 720.There were significant differences between patients with BCRL and healthy controls. The optimal cutoff values for ECF ratios were 1.010 for both the dominant and non-dominant arms. At 1 kHz, the cutoff values of SFBIA were 1.050 and 1.046, and at 5 kHz, those were 1.070 and 1.030 for the dominant and non-dominant affected arms, respectively. The mean + 2SD values for ECF ratio were 1.018 and 1.020 and at 1 kHz, the mean + 2SD values of SFBIA were 1.144 and 1.0135 and at 5 kHz, the cutoff values of SFBIA were 1.141 and 1.124 for the dominant and non-dominant affected arms, respectively. The mean + 3SD values for ECF ratio were 1.026 and 1.030 and at 1 kHz, the mean + 3SD values of SFBIA were 1.206 and 1.203 and at 5 kHz, those were 1.201 and 1.187 for the arms, respectively. The cutoff, mean + 2SD, and mean + 3SD values were applied to 70 patients with unilateral BCRL. When the cutoff values were applied, a higher proportion of BCRL patients were included.When these figures were applied to the patient group, the cutoff values included a higher proportion of patients with lymphedema. Further studies are needed to investigate whether bioimpedance analysis can accurately predict the development of lymphedema.

Background:  The lymphovenous anastomosis (LVA) has become one of the treatment options for lymphedema. However, it is regarded as a difficult surgery that many young microsurgeons are reluctant to try. This report investigates the learning curve in regard to symptom improvement., Methods:  This is a retrospective analysis performed in 33 consecutive lymphedema patients (38 extremities) who underwent only LVAs from August 2010 to February 2016. Surgical outcomes in regard to surgeon's experience were evaluated. The surgeons experience was divided into three groups: early group with less than 2 years, moderate with 2 to 4 years, and mature group with more than 4 years of experience., Results:  A total of 31 limbs (8/8 in upper extremity and 23/30 in lower extremity) showed improvement. When we compare volume change and recurrence of cellulitis with regard to surgeon's experience, there were no statistically significant differences. However, the mean time per LVA was significantly decreased as the experience increased over time ( p  = 0.017)., Conclusion:  LVA is an effective treatment option to reduce the volume in the affected limb and to improve symptoms involved. Regardless of the number and experience of the surgeons, cellulitis improves significantly after LVA. The experience of the surgeon does not significantly impact the positive outcome while proficiency increases with experience., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Rationale: Paraneoplastic syndrome is a very rare syndrome among prostate cancer patients. In particular, paraneoplastic sensorimotor neuropathy has never been reported as a complication of prostatic adenocarcinoma., Patient Concerns: A 75-year-old man who was diagnosed with prostatic adenocarcinoma with multiple metastases received cancer treatment. But, numbness and tingling sensations in both sides of the upper and lower limbs got progressively worse., Diagnosese: He was diagnosed with positive anti-Hu antibodies paraneoplastic sensorimotor polyneuropathy caused by prostatic adenocarcinoma., Interventions: The patient received physical therapy, occupational therapy, and opioid medication during 3 weeks at cancer rehabilitation department during 3 weeks., Outcomes: There was no improvement in functional outcome in this patient. But, the patient's neuropathic pain was improved by the use of opioid agents., Lessons: This case report is the first to report anti-Hu antibody-positive paraneoplastic sensorimotor neuropathy in a patient with adenocarcinoma of the prostate.

Objective: The purpose of this study was to investigate the effects of a complex rehabilitation (CR) program and complex decongestive therapy (CDT) on edema status, physical function, and quality of life in patients with unilateral lower-limb lymphedema after gynecologic cancer surgery., Methods: In this randomized pilot study, 40 patients with secondary unilateral lymphedema, after gynecologic surgery for cervical, endometrial, or ovarian cancer, that had been diagnosed based on clinical assessment and 10% volume differences between the legs were randomly assigned to the CDT (n=20) and CDT combined with CR (CRCDT; n=20) groups. CR comprised stretching, strengthening, and aerobic exercises performed for 40min, five times a week for 4weeks. Intensive CDT was administered by a physical therapist during weeks 0-2 and by the patients themselves during weeks 2-4. Limb volume, bioimpedance, muscular strength, EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30) score, 30-s chair stand test, muscular strength, and GCLQ-K (Korean version of the Gynecological Cancer Lymphedema Questionnaire) score were assessed at baseline and after 4weeks of treatment., Results: The edema status, fatigue, pain, and GCLQ-K scores were significantly improved in both groups after the 4-week intervention (P<0.05). Physical function and fatigue in EORTC QLQ-C30 and the 30-s chair stand test and quadriceps muscle strength were significantly improved in the CRCDT group compared with the CDT group (P<0.05)., Conclusions: CR improves physical function, fatigue, and muscular strength without increasing edema status in patients with unilateral lower-limb lymphedema after gynecologic cancer surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The present study investigated the prevalence and risk factors of adhesive capsulitis of the shoulder in breast cancer patients between 13 and 18 months after surgery., Methods: This study included 271 women who underwent surgery for breast cancer with a postoperative period of 13-18 months. Current adhesive capsulitis was defined as restriction of external rotation and one or more additional directional restrictions with history of shoulder pain. Cumulative adhesive capsulitis was defined as current adhesive capsulitis or a previous history of adhesive capsulitis after breast cancer surgery. Multivariate logistic regression analysis was performed to examine associations between current or cumulative adhesive capsulitis and potential risk factors., Results: Among the 271 study patients, 28 (10.3%) and 21 (7.7%) had cumulative or current adhesive capsulitis, respectively. The incidences of cumulative and current adhesive capsulitis were higher in those aged 50-59 years (odds ratio [OR], 9.912; 95% confidence interval [CI], 1.790-54.880; and OR, 12.395; 95% CI, 1.187-129.444, respectively) and those who underwent mastectomy (OR, 6.805; 95% CI, 1.800-25.733; and OR, 9.645; 95% CI, 2.075-44.829, respectively) or mastectomy with reconstruction (OR, 13.122; 95% CI, 2.488-69.218; and OR, 20.075; 95% CI, 2.873-140.261, respectively)., Conclusions: Adhesive capsulitis of the shoulder is a common problem after breast cancer treatment. An age of 50-59 years and mastectomy are major risk factors for adhesive capsulitis, and breast reconstruction additionally increases the risk. Patients with these risk factors require greater attention for early diagnosis and proper treatment.

[Purpose] To evaluate differences in pectoral muscle tightness according to arm abduction angle and to determine the best arm abduction angle for stretching of pectoral muscle tightness in breast cancer patients. [Subjects and Methods] Horizontal abduction differences of shoulders were measured bilaterally by arm abduction to 45°, 90°, and 135° to determine the best arm abduction angle for measuring pectoral muscle tightness. Thirty-two patients were divided into three pectoral muscle stretching groups (A: 45°, B: 90°, and C: 135°). We measured the shoulder range of motion, scores of the Disabilities of the Arm, Shoulder, and Hand, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and the Breast Module, and pain levels (using a visual analog scale) before and after therapy. [Results] The differences in degree of horizontal abduction between shoulders were significantly larger for arm abduction to 90° and 135° than that to 45°. Groups B and C showed greater improvements in horizontal abduction limitations than group A. [Conclusion] Horizontal abduction differences between shoulders are prominent when arms are abducted to 90° and 135°. The appropriate arm abduction angle for measuring horizontal abduction and effective stretching of pectoral muscle tightness may be >90°.

Purpose: The aim of this study was to evaluate the effects of physical therapy (PT) combined with manual lymphatic drainage (MLD) on shoulder function, pain, lymphedema, visible cords, and quality of life (QOL) in breast cancer patients with axillary web syndrome (AWS)., Methods: In this prospective, randomized trial, 41 breast cancer patients with visible and palpable cords on the arm and axilla and a numeric rating scale (NRS) pain score of >3 were randomly assigned to PT (3 times/week for 4 weeks; n = 20) and PT combined with MLD (5 times/week for 4 weeks; PTMLD; n = 21) groups. MLD was performed by a physical therapist and the patients themselves during week 1 and weeks 2-4, respectively. Arm volume, shoulder function (muscular strength; active range of motion; and disabilities of the arm, shoulder, and hand [DASH]); QOL (European Organization for Research and Treatment of Cancer Core and Breast Cancer-Specific QOL questionnaires), and pain (NRS) were assessed at baseline and after 4 weeks of treatment., Results: QOL including functional and symptom aspects, shoulder flexor strength, DASH, and NRS scores were significantly improved in both groups after the 4-week intervention (P < 0.05). NRS score and arm volume were significantly lower in the PTMLD group than in the PT group (P < 0.05). Lymphedema was observed in the PT (n = 6), but not PTMLD, group (P < 0.05)., Conclusions: PT improves shoulder function, pain, and QOL in breast cancer patients with AWS and combined with MLD decreases arm lymphedema.

The aim of the present study was to investigate the therapeutic mechanism of low-level laser therapy (LLLT) in the mouse tail lymphedema model. Six-week-old female mice were classified into the laser treatment group, sham treatment group, and surgical control group (10 mice per group). LLLT was administered daily for 10 min from the surgical day to 11 days (12 times). Macrophage activation and lymphatic vessel regeneration were evaluated through immunohistochemical staining with anti-F4/80 and anti-LYVE-1 antibodies, respectively, at 12 days post-procedure. Quantitative real-time polymerase chain reaction (qPCR) was performed to measure messenger RNA (mRNA) expression of vascular endothelial growth factor A, B, C, R1, R2, and R3 (VEGF-A, VEGF-B, VEGF-C, VEGFR1, VEGFR2, and VEGFR3) at 12 days post-procedure. Student's t and one-way ANOVA tests were performed for statistical analyses. Significance was defined as p < 0.05. The thickness of the tail rapidly increased until 6 days in the laser and sham groups. The mice in the laser group showed a significantly decreased thickness compared with the sham group at 10 and 12 days. Immunohistochemistry assay revealed that LLLT reduced inflammation and induced new lymphatic vessel growth. qPCR showed that expressions of VEGFR3 were (p = 0.002) increased in the laser group. These results suggest that LLLT has anti-inflammatory and lymphangiogenetic effects for the management of lymphedema.

Purpose: The purpose of this study was to assess clinical practice and barriers associated with cancer rehabilitation from the perspective of Korean physiatrists., Materials and Methods: All active members of the Korean Academy of Rehabilitation Medicine were invited to complete an online survey developed after focus group discussions., Results: A total of 97 physiatrists (72 males and 25 females) in Korea completed the survey. Of these, 77% reported familiarity with the term 'cancer survivors.' More than 50% of respondents reported that they provided rehabilitation services for patients with breast cancer (61.9%), brain tumors (64.9%), and spinal tumors (63.9%), whereas 86.6% of respondents reported that they had never or rarely provided rehabilitation programs for patients with gynecological, colorectal, or prostate cancer. Physiatrists who received referrals from a well-organized cooperative referral system reported providing services such as exercise programs for patients with gynecological cancer (odds ratio [OR], 2.16; p=0.044) as well as education regarding lymphedema (OR, 1.81; p=0.047) and neuropathic pain (OR, 1.96; p=0.026)., Conclusion: Although most of the physiatrists surveyed believed that they should contribute to the management of cancer patients, they considered themselves ill equipped to provide appropriate rehabilitation services. This lack of understanding of the effectiveness of rehabilitation services for cancer patients and absence of a cooperative referral system are the major barriers to providing rehabilitation services to cancer survivors in Korea.

Objective: This study of pressure monitoring of multilayer inelastic bandaging and the effect of padding in breast cancer-related lymphedema patients aimed to measure the resting and working sub-bandage pressures in compression therapy for lymphedema patients and to determine whether applying additional padding has an additional effect in volume reduction of the limb., Design: Forty-eight patients with breast cancer who were beginning complex decongestive therapy for lymphedema were included. In 24 patients, padding was added to the forearm. A short-stretch bandage with or without padding was applied to the affected arm. The working pressure was measured while the patients squeezed a rubber device. The forearm limb circumference was measured before and after 2 wks of treatment., Results: The mean (SD) of the resting pressure was 36.3 (2.2) mm Hg without padding and 49.5 (3.2) mm Hg with padding. The mean (SD) of the working pressure was 9.5 (3.7) mm Hg without padding and 24.3 (9.1) mm Hg with padding (P < 0.05). The volume loss after treatment was significantly greater in the group with added padding (P < 0.05)., Conclusions: The working pressure during exercising with a force of 50 Pa is approximately 10 mm Hg with a short-stretch bandage applied. Adding a pad increases both the resting and the working pressure and also seems to be effective in increasing volume reduction of the limb.

We reviewed the findings of a video fluoroscopic swallowing study (VFSS) of 28 patients with vocal cord paralysis (VCP) who complained of swallowing difficulties. VFSSs were performed with thick and thin liquid using modified Logemann methods. The patients were grouped according to whether their VCP was of central or peripheral origin, and the VFSS findings of the groups were compared. The patients showed oral phase dysfunction and pharyngeal dysfunction, especially when the cause was of central origin. Oral phase abnormalities were found in 13 patients and pharyngeal phase abnormalities were found in all patients, including penetration in 20 patients and aspiration in 14 patients. Improper lip closure (LC) and bolus formation (BF) and a delay in triggering pharyngeal swallow (TPS) and upper esophageal sphincter release (UESR) were significantly more frequent in patients with central VCP. With thin-liquid swallowing, pharyngeal transit time (PTT) and pharyngeal delay time (PDT) were significantly more prolonged in central VCP. The results suggest that the delay in triggering and poor coordination of swallowing were profound in patients with central VCP, but dysfunction in peripheral VCP may originate from poor pharyngeal movement.