A phase III, multicenter, single-arm study to assess the utility of indocyanine green fluorescent lymphography in the treatment of secondary lymphedema.

OBJECTIVE: Indocyanine green (ICG) fluorescent lymphography might be useful for assessing patients undergoing lymphatic surgery for secondary lymphedema. The present clinical trial aimed to confirm whether ICG fluorescent lymphography would be useful in evaluating lymphedema, identifying lymphatic vessels suitable for anastomosis, and confirming patency of lymphaticovenular anastomosis in patients with secondary lymphedema. METHODS: The present phase III, multicenter, single-arm, open-label, clinical trial (HAMAMATSU-ICG study) investigated the accuracy of lymphedema diagnosis via ICG fluorescent lymphography compared with lymphoscintigraphy, rate of identification of lymphatic vessels at the incision site, and efficacy for confirming patency of lymphaticovenular anastomosis. The external diameter of the identified lymphatic vessels and the distance from the skin surface to the lymphatic vessels using preoperative ICG fluorescent lymphography were measured intraoperatively under surgical microscopy. RESULTS: When the clinical decision for surgery at each research site was made, the standard diagnosis of lymphedema was considered correct. For the 26 upper extremities, a central judgment committee who was unaware of the clinical presentation confirmed the imaging diagnosis was accurate for 100.0% of cases, whether the assessments had been performed via lymphoscintigraphy or ICG lymphography. In contrast, for the 88 lower extremities, the accuracy of the diagnosis compared with the diagnosis by the central judgment committee was 70.5% and 88.2% for lymphoscintigraphy and ICG lymphography, respectively. The external diameter of the identified lymphatic vessels was significantly greater in the lower extremities than in the upper extremities (0.54 ± 0.21 mm vs 0.42 ± 0.14 mm; P < .0001). Also, the distance from the skin surface to the lymphatic vessels was significantly longer in the lower extremities than in the upper extremities (5.8 ± 3.5 mm vs 4.4 ± 2.6 mm; P = .01). For 263 skin incisions, with the site placement determined using ICG fluorescent lymphography, the rate of identification of lymphatics vessels suitable for anastomosis was 97.7% (95% confidence interval, 95.1%-99.2%). A total of 267 lymphaticovenular anastomoses were performed. ICG fluorescent lymphography was judged as "useful" for confirming patency after the anastomosis in 95.1% of the cases. CONCLUSIONS: ICG fluorescent lymphography could be useful for improving the treatment of patients with secondary lymphedema from the outpatient setting to surgery.

HAMAMATSU-ICG study: Protocol for a phase III, multicentre, single-arm study to assess the usefulness of indocyanine green fluorescent lymphography in assessing secondary lymphoedema.

INTRODUCTION: Secondary lymphoedema of the extremities is an important quality-of-life issue for patients who were treated for their malignancies. Indocyanine green (ICG) fluorescent lymphography may be helpful for assessing lymphoedema and for planning lymphaticovenular anastomosis (LVA). The objective of the present clinical trial is to confirm whether or not ICG fluorescent lymphography using the near-infrared monitoring camera is useful for assessing the indication for LVA, for the identification of the lymphatic vessels before the conduct of LVA, and for the confirmation of the patency of the anastomosis site during surgery. METHODS AND ANALYSIS: This trial is a phase III, multicentre, single-arm, open-label clinical trial to assess the efficacy and safety of ICG fluorescent lymphography when assessing and treating lymphoedema of patients with secondary lymphoedema who are under consideration for LVA. The primary endpoint is the identification rate of the lymphatic vessels at the incision site based on ICG fluorescent lymphograms obtained before surgery. The secondary endpoints are 1) the sensitivity and specificity of dermal back flow determined by ICG fluorescent lymphography as compared with 99mTc lymphoscintigraphy-one of the standard diagnostic methods and 2) the usefulness of ICG fluorescent lymphography when confirming the patency of the anastomosis site after LVA. ETHICS AND DISSEMINATION: The protocol for the study was approved by the Institutional Review Board of each institution. The trial was filed for and registered at the Pharmaceuticals and Medical Devices Agency in Japan. The trial is currently on-going and is scheduled to end in June 2020. TRIAL REGISTRATION NUMBER: jRCT2031190064; Pre-results.

Comparison between Negative-Pressure Fixation and Film Dressing in Wound Management after Tissue Expansion: A Randomized Controlled Trial.

Wound compression and fixation are important to reduce scarring. Numerous postoperative treatments have been developed to reduce scar formation; however, a simple and effective device that improves the appearance and histochemical properties of incisional scars is needed. Therefore, the authors have devised a novel method, negative-pressure fixation, that applies negative pressure inside polyurethane foam covered with film. In the present study, negative-pressure fixation was applied to incisional wounds resulting from the insertion of a tissue expander in patients undergoing two-stage breast reconstruction. The authors aimed to evaluate the effects of negative-pressure fixation on scar appearance and histochemical properties in comparison to those for film dressing without negative pressure. A prospective, open-label, randomized, single-center study was performed. A half-side test was conducted on the incisional scar resulting from tissue expander insertion during breast reconstruction after mastectomy in 13 female patients. The dressings on both sides of the scar were replaced once per week until the tissue expander was adequately inflated. The outcomes were assessed 6 months later. Scars were photographed before the second operation and were evaluated using a visual analogue scale. All scars were removed and resutured during the final operation, allowing a histochemical analysis. The mean visual analogue scale score for the negative-pressure fixation side was significantly lower compared with that for the film dressing side (p = 0.0025). In addition, the scar on the negative-pressure fixation side was significantly narrower (p = 0.0015). Thus, negative-pressure fixation is a simple and effective device for improving the appearance and histochemical properties of incisional scars.

Lymphatic transit rate as a predictive parameter for nodal metastasis in primary limb malignant melanoma.

BACKGROUND: The status of sentinel lymph node (SLN) is one of the most predictive prognostic factors in patients with clinically localized malignant melanomas (MMs). However, since the positive SLN metastatic rate is as low as 20%, it is desirable to minimize SLN biopsy performance with imaging. By dynamic lymphoscintigraphy, we have proposed the lymphatic transit rate (LTR), the value that the distance between the primary lesion and SLN is divided by scintigraphic saturation time. LTR represents the scintigraphic saturation velocity and can be used for evaluation of metastasis of skin cancers. METHODS: Dynamic lymphoscintigraphy data from 36 lymph nodes in 36 patients with primary MM on the limb were analyzed. The initial sites of the MMs were the lower limb in 24 patients and the upper limb in 12 patients. Histopathologically, nodal metastasis was found in 10 patients. RESULTS: In the lower limb MM, the mean LTRs were 3.49 cm/min in histologically non-metastatic SLNs and 4.49 cm/min in histologically metastatic SLNs (P = 0.0056). In the upper limb MM, the mean LTRs were 2.59 cm/min in non-metastatic SLNs and 3.94 cm/min in metastatic SLNs (P = 0.0162). Thus, significantly higher LTRs were obtained in the metastatic SLNs. All SLNs with LTR < 4.0 cm/min in the lower limb MM and those with LTR < 3.0 cm/min in the upper limb MM were non-metastatic. CONCLUSION: LTR is a useful predictive indicator for nodal metastasis and SLN biopsy performance in MMs.

Evaluation of positron emission tomography imaging to detect lymph node metastases in patients with extramammary Paget's disease.

Patients with extramammary Paget's disease (EMPD) have a relatively good prognosis, when spread of the tumor cells is limited to the epidermis. However, invasive EMPD has a poor prognosis, when the patients have regional lymph node metastasis. Detection of nodal metastasis is thus mandatory to manage EMPD. To evaluate the 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to assess lymph node metastasis, 15 patients with histologically proven primary EMPD were enrolled in this study. All patients underwent whole-body PET prior to sentinel lymph node biopsy (SLNB). The maximum standardized uptake value (SUVmax) of more than 2.5 was evaluated as positive PET indicative of malignancy. Among 14 cases with the primary genital lesions, 11 cases underwent bilateral SLNB of the inguinal nodal basin and the remaining three cases unilateral SLNB. One case with a primary axillary lesion underwent unilateral SLNB of the axillary nodal basin. Therefore, a total of 26 regional basins were investigated. In general, nodal basins can be categorized into four groups: (i) histologically negative and PET negative (true negative); (ii) histologically positive and PET negative (false negative); (iii) histologically positive and PET positive (true positive); and (iv) histologically negative and PET positive (false positive) groups. In the 26 nodal basins, there were 19 true negative and seven true positive cases, and neither false negative nor false positive cases were observed. The mean SUVmax was significantly higher in the true positive basins (8.03 ± 3.34) than in the true negative basins (0.26 ± 0.56). The SUVmax value may be useful for detection of nodal metastasis.

Evaluation of positron emission tomography imaging to detect lymph node metastases in patients with high-risk cutaneous squamous cell carcinoma.

Ten to twenty percent of high-risk cutaneous squamous cell carcinoma (cSCC) can metastasize to regional lymph nodes. Detection of nodal metastasis is mandatory to manage high-risk cSCC. This study was aimed to evaluate the 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to assess lymph node (LN) metastasis of high-risk cSCC patients. Twenty-six patients with histologically proven primary cSCC were enrolled. All patients underwent whole-body PET prior to lymphoscintigraphy and subsequent sentinel LN biopsy. The maximum standardized uptake value (SUVmax) of more than 2.5 is generally evaluated as a positive PET finding indicative of malignancy. On the basis of the histopathological and PET findings, 30 LN from 26 patients were categorized into four groups: (i) histologically negative and PET negative (true-negative; n = 22); (ii) histologically positive and PET negative (false-negative; n = 0); (iii) histologically positive and PET positive (true-positive; n = 3); and (iv) histologically negative and PET positive (false-positive; n = 5). The mean SUVmax was significantly higher in the true-positive cases (11.0 ± 2.8) than in the false-positive cases (3.4 ± 0.6). In the false-positive cases, the number of tumor-infiltrating inflammatory cells at the primary skin site was highest among the four groups, suggesting that inflammation contributed to the false-positive uptake of FDG. Although we cannot negate the possibility of the presence of PET-undetectable micrometastasis, the SUVmax value may be useful for avoidance of excess performance of sentinel LN biopsy.

Lymphatic transit rate as a novel predictive parameter for nodal metastasis in primary truncal skin cancers.

Prediction of nodal metastasis in skin cancer before sentinel lymph node (SLN) biopsies is ideal to avoid unnecessary SLN biopsy performance. Primary truncal skin cancers are characterized by the lymphatic flow that drains from the primary lesion, occasionally to plural nodal basins. The scintigraphic appearance time (SAT), defined as the time between radionuclide injection and first SLN visualization, can potentially predict nodal metastasis, and a short SAT is a predictive parameter for metastasis. We recently introduced a novel method to measure the lymphatic flow rate using dynamic lymphoscintigraphy exhibiting a time-activity curve in the SLN. The time at which the count reaches a plateau in the SLN is termed the scintigraphic saturation time (SST) and can be a good alternative to the SAT. Moreover, the value obtained by division of the distance between the primary lesion and the SLN by the SST was termed the lymphatic transit rate (LTR), which represents the scintigraphic saturation velocity. In the present study, we evaluated LTR as a predictive parameter for nodal metastasis. Data for 22 lymph nodes from 18 patients with primary truncal skin cancers were used. Histopathologically, nodal metastasis was determined in nine nodes of eight patients. Because the mean LTR were 1.84 cm/min in non-metastatic SLN and 2.38 cm/min in metastatic SLN, the LTR was significantly higher in metastatic SLN than in non-metastatic SLN. All SLN with LTR of less than 1.8 cm/min were histopathologically evaluated as non-metastatic. The LTR may be a predictive indicator for nodal metastasis.

Application of a three-microneedle device for the delivery of local anesthetics.

PURPOSE: We investigated the effectiveness of a newly developed device for the delivery of local anesthetics in the treatment of axillary osmidrosis and hyperhidrosis. We developed a device with three fine, stainless steel needles fabricated with a bevel angle facing outside ("three-microneedle device" [TMD]) to release a drug broadly and homogeneously into tissue in the horizontal plane. Use of this device could reduce the risk of complications when transcutaneous injections are undertaken. PATIENTS AND METHODS: Sixteen Japanese patients were enrolled. The mean volume of lidocaine hydrochloride per unit area needed to elicit anesthesia when using a TMD was compared with that the volume required when using a conventional 27-gauge needle. The visual analog scale (VAS) score of needlestick pain and injection-associated pain was also compared. RESULTS: The mean volume of lidocaine hydrochloride per unit area to elicit anesthesia using the TMD was significantly lower than that the volume required when using the conventional 27-gauge needle. The VAS score of needlestick pain for the TMD was significantly lower than that the VAS score for the 27-gauge needle. CONCLUSION: These data suggest that the TMD could be useful for the delivery of local anesthetics in terms of clinical efficacy and avoidance of adverse effects.

Measurement of cutaneous lymphatic flow rates in patients with skin cancer: area extraction method.

Some recent reports have revealed that the long scintigraphic appearance time (SAT), defined as the time between radionuclide injection and first sentinel lymph node (SLN) visualization in lymphoscintigraphy, is a negative predictive parameter of nodal metastasis in patients with melanoma. However, most of the methods used to measure the SAT were ambiguous because they utilized visualization in lymphoscintigraphy. We herein introduce a novel method by which to measure the SAT and lymphatic flow rate. The data of 33 patients with primary skin cancer were used. Sequential images were obtained using dynamic lymphoscintigraphy, and a time-activity curve of the SLN was created. The time at which the counts reached plateau was newly defined as an alternative to the SAT and was termed the scintigraphic saturation time (SST). The figure obtained by division of the distance by the SST was newly defined as an alternative to the lymphatic flow rate and termed the lymphatic transit rate (LTR). The SST was clearly determined. It ranged from 220 to 1430 s (mean, 805 s). Pathological examination revealed nodal metastasis in five patients. In 28 patients without metastasis, the mean LTR was in the order of lower limbs (4.07 ± 0.35 cm/min), upper limbs (2.67 ± 0.33 cm/min), trunk (1.79 ± 0.47 cm/min), and head and neck (1.11 ± 0.22 cm/min). The LTRs were higher in patients with nodal metastasis than those without. This method may be effective for accurate measurement of the SAT and lymphatic flow rate.

Reconstruction for extensive groin hidradenitis suppurativa using a combination of inferior abdominal flap and medial thigh-lift: a case report.

UNLABELLED: Various methods for reconstructing hidradenitis suppurativa of the groin have been reported. However, it is difficult to attain favorable results both aesthetically and functionally. This report describes a case in which a defect was reconstructed using a combination of inferior abdominal flap and medial thigh-lift after radical excision of extensive groin hidradenitis suppurativa. A 37-year-old woman patient underwent radical excision of bilateral groin hidradenitis suppurativa. After the excision, an inferior abdominal flap and bilateral medial thigh flaps were created and advanced to close the defect. The operative procedure was simple and did not require a donor site. The postoperative scar coincided with the inguinal folds and was concealed by undergarments. No functional disorder remained. Reconstruction for extensive groin hidradenitis suppurativa using this method can attain good aesthetic and functional results. The combination of inferior abdominal flap and medial thigh-lift is potentially a useful option for reconstruction of extensive groin hidradenitis suppurativa. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Free jejunal flap transfer for pharyngoesophageal reconstruction in patients with intestinal malrotation: two case reports.

Intestinal malrotation results from failure of intestinal rotation and fixation during fetal life. We report two cases of esophageal reconstruction with free jejunal flaps following total laryngopharyngectomy of hypopharyngeal and cervical esophageal carcinoma in which intestinal malrotation was detected during the jejunal flap harvesting. In both cases, the ligament of Treitz was absent, and the laparotomy incision was thus extended to identify the jejunum. In case 1, harvesting an adequate length of the vascular pedicle of the flap was impossible because of the abnormal position of the pancreas; thus, a jejunal flap of maximal length was harvested for optimal pedicle positioning in the recipient site. In case 2, Ladd's ligament prohibited the release of the jejunum from the ascending colon and required its dissection. Both patients underwent successful reconstruction. When the ligament of Treitz is absent during jejunal flap harvesting, investing the whole bowel by extended laparotomy incision is recommended. When anatomical abnormality caused by intestinal malrotation is detected, releasing an adhesion of the jejunum from circumferential organs and identifying the adequate vascular pedicle of a jejunal flap are necessary. If harvesting the long vascular pedicle is impossible, a jejunal flap of maximal length should be harvested for optimal positioning for vascular anastomosis at the shortest distance in the recipient site.

Reconstruction of lateral mandibular defect: a comparison of functional and aesthetic outcomes of bony reconstruction vs soft tissue reconstruction - long-term follow-up.

CONCLUSION: Reconstruction with a vascularized bone flap provided superior postoperative outcomes compared with reconstruction with a soft tissue free flap. However, patients obtained acceptable long-term functional outcomes even with a soft tissue free flap and this method is an option in selected patients. A multidisciplinary approach involving dental treatments and nutrition education is important to improve postoperative function. OBJECTIVE: To assess the postoperative outcomes of two different options for reconstruction of the lateral mandible using bony or soft tissue reconstruction. METHODS: We divided 25 patients into 2 groups on the basis of the type of reconstruction following lateral mandibulectomy. Twelve patients underwent reconstruction using a vascularized fibular flap and 13 patients received a soft tissue free flap. We compared the postoperative functional and aesthetic outcomes and examined the time-dependent change in functional outcomes in both groups. RESULTS: Reconstruction with a vascularized bone flap was significantly superior to reconstruction with a soft tissue free flap in deglutition and aesthetic results. There was no significant difference in speech function between the groups. Deglutition in both groups improved markedly over time and all but one patient tolerated a normal or soft diet, including those in the soft tissue reconstruction group. Denture fabrication and recreating occlusion explained the improved deglutition.

Delayed distally based sural flap with temporary venous supercharging.

The distally based sural flap has become popular for reconstruction of the foot and leg. However, this flap often fails due to venous congestion. In this report, we developed a new modification of the distally based sural flap. The procedure comprised three stages. In the first stage, the flap was raised cephalad to the midpoint of the posterior aspect of the leg, involving reanastomosis of the short saphenous vein (SSV) at the proximal end of the flap. In the second stage, ligature of the SSV was performed. In the third stage, the entire flap was raised. We treated eight patients with the flap. All flaps survived completely. Duplex scanning indicated that venous drainage of the flap was provided by the tenuous venae comitantes (VCs) surrounding the SSV. Reanastomosis of the SSV may prevent rapid venous overloading of the VCs. Our new modification may be useful to avoid venous congestion.

Reading man flap: application to plantar defects.

The plantar surface of the foot has highly specialized, densely adherent, glabrous skin, making functional replacement difficult. Glabrous skin defects should be replaced with similar skin to restore function and aesthetics. An innovative technique, the "reading man flap," was developed for closure of circular skin defects. At locations such as the face, trunk, thigh, and calf, the "reading man" procedure provides tension-free closure with minimal additional healthy skin excision, and it does not cause "dog ear" formation. The potential exists for replacement of plantar defects with skin of the same quality using this procedure. In the present study, we report on 2 clinical cases in which intermediate-size plantar defects were reconstructed using the reading man flap. This method can provide tissue as durable, yet as sensitive, as skin that matches the unique characteristics of the plantar skin.

CXCL10 produced from hair follicles induces Th1 and Tc1 cell infiltration in the acute phase of alopecia areata followed by sustained Tc1 accumulation in the chronic phase.

BACKGROUND: Alopecia areata (AA) is an organ-specific and cell-mediated autoimmune disease. T lymphocytes densely surround lesional hair bulbs, which is histologically referred to as "swarm of bees". However, pathomechanisms of "swarm of bees" are still uncertain. OBJECTIVE: We investigated the pathological mechanisms of "swarm of bees", focusing on T-cell chemotaxis so that inhibition of chemotaxis may be strong candidate of novel treatments for AA. METHODS: We investigate the expression of chemokine receptors on T cells obtained from peripheral blood mononuclear cells (PBMCs) and skin infiltrating cells in AA patients. In addition, real-time chemotaxis assay was also demonstrated. RESULTS: In PBMCs, the frequency of CXCR3+CD4+ T cells (Th1) was significantly higher in acute-phase AA than in chronic-phase AA or healthy control, while CXCR3+CD8+ T cells (Tc1) were significantly increased in chronic-phase AA. In the skin lesions of acute-phase AA, CXCR3+CD4+ and CXCR3+CD8+ T cells infiltrated in the juxta-follicular area. In chronic-phase AA, CXCR3+CD8+ T cells dominated the infiltrate around hair bulbs, possibly contributing to the prolonged state of hair loss. Lymphocytes obtained from a lesional skin of acute-phase AA contained CXCR3+CD4+ and CXCR3+CD8+ T cells at higher percentages than those of PBMCs, suggesting preferential emigration from the blood. Immunohistochemical and real-time RT-PCR studies demonstrated that hair follicles of acute-phase AA expressed a high level of Th1-associated chemokine CXCL10. By chemotaxis assay, freshly isolated PBMCs from acute-phase AA patients had a strong velocity of chemotaxis toward CXCL10 with increased expression of F-actin. CONCLUSIONS: These results suggest that the increased production of CXCL10 from hair follicles induces preferential infiltrates of highly chemoattracted Th1 and Tc1 cells in the acute phase of AA, and Tc1 infiltration remains prolonged in the chronic phase.