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Introduction: Treatment for patients with comorbid lymphedema and varicose veins is controversial. Surgical options for these patients are limited. The study was aimed to investigate the validity o...

Background Lymphatic venous anastomosis (LVA) is a widely accepted surgical procedure for lymphedema. To obtain the best outcomes, surgeons should be well trained. A recent study introduced an LVA training model using pig trotters for their utility and structural similarity to human tissues. However, details regarding the utilization of anastomosis models, such as feasible points for training based on vessel anatomy, have not been clarified. Therefore, we assessed the anatomical details of lymphatic vessels and veins of trotters to establish a practical training model of LVA. Methods Ten frozen trotters were used. After thawing at room temperature, indocyanine green fluorescent lymphography was used to visualize the lymphatic course. To dissect the lymphatic vessels and veins from the distal to the proximal end, whole skins were detached thoroughly from the plantar side. Data from the lymphatic vessels and veins were collected based on their courses, diameters, and layouts to clarify adjacent points feasible for LVA training. Results Both lymphatic vessels and veins were classified into four major courses: dorsal, medial, lateral, and plantar. The majority were dorsal vessels, both lymphatic vessels and veins. The adjacent points were always found in the distal dorsum center and were especially concentrated between the metacarpophalangeal (MP) joint and central interphalangeal crease, followed by the medial and lateral sides. Conclusion The most relevant point for LVA surgical training in the trotter was the dorsal center distal to the MP joint, where parallel vessels of similar sizes were found in all cases. This practical LVA surgical model would improve surgeon skills in not only anastomosis but also preoperative fluorescent lymphography.

We have previously reported that patients with idiopathic primary lymphedema of adult onset can be classified into an older group with bilateral involvement and a younger group with unilateral involvement and that there are significant differences in the characteristics of these groups. The aims of this study were to investigate the features of these two groups further by evaluating the lymphatics while performing lymphaticovenular anastomosis (LVA) and to compare the effectiveness of LVA between the two groups.This study enrolled 74 patients (136 edematous legs) in whom indocyanine green (ICG) lymphography and LVA were performed. The rate of detection and the diameter of the lymphatic vessels were recorded. The lower extremity lymphedema index (the total sum of the squares of the circumference for five areas in each leg divided by the body mass index) was obtained before and 6 months after LVA. The rate of improvement in the affected lower limbs after LVA was also calculated.The clinical lymphedema pattern was determined to be bilateral in 62 patients and unilateral in 12. Patients with bilateral lymphedema were significantly older than those with unilateral lymphedema (77.1 ± 7.8 years vs 55.5 ± 12.77 years; P .01). A linear pattern was seen in 23 patients (46 legs), a low enhancement (LE) pattern in 12 patients (24 legs), a distal dermal backflow (dDB) pattern in 20 patients (40 legs), and an extended dermal backflow (eDB) pattern in 7 patients (14 legs). The lymphedema was unilateral in 12 patients (12 legs). There were significant between-group differences in lymphatic diameter in relation to lower leg area: linear (0.9 ± 0.1 mm) vs dDB (0.7 ± 0.2 mm), linear vs eDB (0.7 ± 0.2 mm), linear vs unilateral (0.5 ± 0.1 mm), LE (0.9 ± 0.2 mm) vs dDB, LE vs eDB, LE vs unilateral, and dDB vs unilateral, P .01; and eDB vs unilateral, P .05. There were also significant between-group differences in the rate of improvement in the lower extremity lymphedema index according to the ICG lymphography pattern and laterality: linear (10.5% ± 2.4%) vs unilateral (6.7% ± 0.6%), LE (10.4% ± 1.5%) vs unilateral, dDB (11.0% ± 1.3%) vs eDB (8.9% ± 1.5%), and dDB vs unilateral, P .01; linear vs eDB, P .05; and eDB vs unilateral, P .05.The lymphatic vessel diameter tended to be greater in older patients with bilateral lymphedema than in younger patients with unilateral lymphedema. The rate of detection and improvement tended to decrease with worsening of the ICG lymphography pattern. LVA is thought to be more effective in older patients with early-stage bilateral lower leg lymphedema than in their younger counterparts with late-stage unilateral lymphedema.

Objective Once established, lymphorrhea typically persists and can present as an external lymphatic fistula. Lymphorrhea occurs in limbs with severe lymphedema, as a complication after lymphatic damage, and in obese patients. Some cases are refractory to conservative treatment and require surgical intervention. Reconstruction of a lymphatic drainage route is considered ideal treatment for lymphorrhea. In this study, we reviewed the efficacy of lymphaticovenous anastomoses as a treatment for lymphorrhea of any etiology. Patients & Methods The study included 12 patients with lymphorrhea: primary lymphedema (n=3), age-related lymphedema (n=4), lymphorrhea due to lipedema (n=3), or iatrogenic lymphorrhea (n=2). Compression therapy had been performed preoperatively in 10 patients. Compression therapy was difficult to apply in 2 patients. The lymphatic vessels and the veins were anastomosed end-to-end using 12-0 nylon suture under a microscope. Results The lymphaticovenous anastomosis was successful in all cases and there were no perioperative complications. The volume of lymphorrhea decreased within 5 days after the surgery in all cases and resolved completely by 2 weeks postoperatively. The compression therapy applied preoperatively was continued postoperatively. There has been no postoperative recurrence of lymphorrhea or cellulitis.

When reconstructing a congenital floating thumb, we describe two children in whom preservation of all five digits is achieved through successful transfer of a thoracodorsal artery perforator (TAP) flap and vascularized scapula. Key words: Chimera flap, congenital anomaly, floating thumb, hand, thumb

A drawback of multiple lymphaticovenular anastomoses (LVAs) is the need for at least two microsurgeons and the same number of microscopes. In practice, many hospitals find it difficult to access such resources. We have developed a novel line production system (LPS) to address this problem. We assessed whether or not the LPS is better than the conventional dual microscope (DM) system when performing multiple LVAs.An LPS group, wherein a novice microsurgeon used loupes to dissect lymphatics and an expert microsurgeon used a microscope to perform the LVAs, and a DM (control) group, wherein the surgeons used microscopes to perform the LVAs. We recorded the lymphatic detection rate through the loupes and the diameter of the detected lymphatics. We also investigated the impact of using the LPS by comparing the number and quality of LVAs and improvement in lymphedema between the study groups.The mean lymphatic detection rate was 81%±15.60%, and the mean size of lymphatics was 0.44 ± 0.12 mm in the LPS. The number of LVAs/h in LPS was significantly higher than that in DM (2.15 ± 0.20 vs. 1.38 ± 0.17; p 0.01). The number of successful LVAs/h in LPS was significantly higher than that in the DM (2.08 ± 0.22 vs. 0.84 ± 0.14; P 0.01). Mean rate of improvement in LEL index was significantly higher than that in DM (9.36 ± 1.85 vs. 6.93 ± 1.73; P 0.01).The number and quality of the LVAs increase using the LPS, which leads to further improvement in lymphedema, with fewer microscopes and microsurgeons and a shorter operating time.

Size distribution and mapping analyses of Ag and Au nanoparticles (NPs) have been made using an ICP-MS combined with laser ablation sampling technique (LA-ICP-MS). With the femtosecond laser (Ti:S laser) ablation system, the measured size distribution was modified to be smaller, whereas this disintegration could be reduced when the nanosecond laser (ArF Excimer laser) ablation was employed. This suggests that both the size and position of the NPs can be defined by the nanosecond LA-ICP-MS technique. More importantly, based on the peak-height analyses (PHA) of the measured signal intensity profiles, the present form of the analytes, whether particulate or ionic form, could be defined. This is very important to investigate the transport of the NPs within biological samples. To demonstrate the unique feature of the technique, imaging analyses of Ag and Au NPs, together with distribution analysis of the ionic form, were conducted on onion cells, prepared through dosing experiments of the Ag and Au NPs. There were clear differences in both the increasing rates of the numbers of NPs and the concentration range of the ionic form between the Ag and Au. The data obtained here demonstrate clearly that the LA-ICP-MS technique can become a major analytical tool to obtain both the size distribution and position of NPs from tissue samples.

Key Clinical Message Replantation combined with simultaneous ectopic implantation can be considered in patients with multiple finger amputation injury. This technique has the advantages of reducing the operating time and optimizing hemodynamic stability. However, it is only possible when multiple hand and microsurgery team can be organized at short notice.

Lymphaticovenous anastomosis (LVA) is now a common treatment for lymphedema. It is important to create as many bypasses as possible to maximize the efficacy of LVA. We have developed a method whereby nylon monofilaments are placed inside the vessel lumen to act as dilators. We refer to this technique as mechanical dilation (MD) to distinguish it from intravascular stenting. In this study, we investigated the efficacy of the conventional supermicrosurgery technique performed with and without MD as a treatment for lower limb lymphedema. The LVA was performed using conventional supermicrosurgery alone in 10 patients (group without MD) and in combination with MD in another 10 patients (group with MD). The mean number of successful LVAs performed per hour was significantly higher in the group with MD than in the group without MD (1.42 ± 0.16 vs 1.14 ± 0.15; P < 0.05). The mean amount of improvement in the lower extremity lymphedema index was significantly greater in the group with MD than in the group without MD (7.34 ± 1.57 vs 4.41 ± 1.53; P = 0.003 < 0.05). A statistically significant correlation was found between the number of successful LVAs and amount of improvement in lymphedema (r = 0.449, P = 0.047 < 0.05). Our findings suggest that use of MD does not shorten the operating time or increase the number of LVAs that can be performed but may make it possible to increase the number of successful LVAs that can be performed between vessels with a diameter of less than 0.3 mm. Use of MD could increase the improvement rate of lymphedema to a greater extent than that achieved by conventional microsurgery alone.

Background: A new method “fascicular turn over method” using vascularized fascicular flap was used for repairing nerve gaps. Following the recent development of supramicrosurgical techniques appropriate for the microanatomy of peripheral nerves, a new method of intraoral “cross-face nerve transfer” was successfully used for repairing trigeminal nerve palsy.

Supplemental Digital Content is available in the text., Summary: Although the great toe plays important roles in walking, loading, and maintaining balance when compared with other toes, there are few reports on great toe reconstruction, including the reconstruction of distal phalanx. This report aims to describe the use of a superficial circumflex iliac artery perforator (SCIP)–osteocutaneous flap for reconstructing a complex tissue defect of the great toe. A 62-year-old man presented with a crush injury to the forefoot. Because the great toe was severely crushed, the defect distal to the proximal phalanx of the great toe was reconstructed using a SCIP-osteocutaneous flap. The immediate postoperative course was uneventful; however, surgical revision was necessary. Signs of osseous union could be observed on radiographic images taken 2 months after the initial surgery. Twenty-four months after surgery, the patient could freely walk without resorption of the transferred bone. We demonstrated that SCIP-osteocutaneous flaps may be promising free flaps in complex tissue defect reconstruction of the great toe.

Supplemental Digital Content is available in the text., Background: Although patients with obesity-induced lymphedema can be treated by weight loss therapy, they find it difficult to lose the required amount of weight. The aims of this study were to clarify the characteristics of the lymphatic vessels in patients with obesity-induced lymphedema and to determine the feasibility and efficacy of lymphovenous anastomosis (LVA) in these patients. Methods: Twenty-two patients (44 edematous lower limbs) with a body mass index (BMI) >35 kg/m2 (obese group) and 91 patients with lymphedema (141 edematous lower limbs) and BMI

Supplemental Digital Content is available in the text., Summary: Treating burn scar contractures is challenging. Although free flap transfer is an effective tool for hand reconstruction, free flaps are often bulky, causing functional disturbance and poor cosmetic appearance. Secondary debulking operations are required, resulting in a prolonged total treatment period and delayed return to daily life and work for the patient. Therefore, 1-stage reconstruction using a thin and pliable flap is ideal. In this report, we present the superthin TDAP flap as an option for the reconstruction of postburn palmar contracture. During TDAP flap elevation, the thoracodorsal artery perforator was identified and traced distally until its penetration into the dermis. Subsequently, the subdermal tissue was removed and a uniformly superthin TDAP flap was elevated. Postoperatively, early functional recovery was achieved with excellent palmar contour and texture. No revision surgery was required and no recurrence of contractures occurred during the 6-month follow-up. This procedure is useful in elevating a superthin TDAP flap and is a feasible option for the reconstruction of working surfaces, such as the palm.

Summary Introduction For successful lymphaticovenous anastomosis (LVA), it is important to create anastomoses with high flow to maintain patency. To ensure that this can be achieved, we compared the efficacy of a modified intraoperative distal compression (IDC) technique with the conventional no compression (NC) method for lower limb lymphedema. Patients and Methods In the IDC group, compression was applied to an area of the foot distal to the first LVA site. After completion of the first LVA, the distal compression was extended over the first LVA site to the distal end of the second LVA site. Results There was no significant difference between the IDC (n = 25) and NC (n = 25) groups in detection rate. However, significant differences were observed in lymphatic vessel diameter and LVA success rate. No intraoperative anastomotic obstruction was seen at the conclusion of surgery. Intraoperative congestion with blood was detected in lymphatic vessels in 8 of 79 anastomoses (10.1%) in the NC group, but not in any cases in the IDC group (p = 0.002). There was a significant between-group difference in the rate of improvement in lymphedema between the IDC (16.1±3.6) and NC groups (14.0±3.4; p = 0.03). Discussion IDC during LVA is thought to increase lymph flow in larger caliber lymphatics, leading to a high success rate and a low rate of venous reflux. IDC is beneficial when performing LVA.

Summary Background Pelvic lymphoceles are the most common complications after pelvic lymphadenectomy. Microsurgical procedures have attracted attention as an alternative treatment for lymphoceles. Here, we report six cases of refractory lymphoceles that were successfully treated using lymphovenous anastomosis. Methods Six patients underwent surgery for gynecologic cancers and developed pelvic lymphoceles, which did not respond to conventional treatment. We mainly performed lymphovenous anastomosis on the ipsilateral lower limbs, although some procedures were also performed on the contralateral limbs. The lymphocele volume change after lymphovenous anastomosis was examined using computed tomography and compared using the Wilcoxon test. Results Five of the six refractory lymphocele cases were successfully treated using lymphovenous anastomosis, and the remaining case exhibited an 87% reduction in lymphocele volume. The average numbers of anastomoses were 6.7 on the ipsilateral side and 2.8 on the contralateral side (the median numbers: 6 [range: 5-9] vs. 3 [range: 1-4], P=0.034). The average lymphocele volume significantly decreased from 414.0 mL preoperatively to 8.0 mL postoperatively (the median lymphocele volume: 255.8 [range: 61.5-1,329.2] vs. 0 [range: 0-47.7], P=0.0313). Conclusion We found that microsurgical treatment was potentially effective for lymphoceles that did not respond to conventional treatment.

Background Pembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50% [1]. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown. Methods We retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) > 50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018. The study included 11 hospitals, which participated in the Hanshin Oncology clinical Problem Evaluation group (HOPE). We analyzed the differences between responders and non-responders in terms of age, sex, performance status score, degree of progression, histological type, smoking history, expression of PD-L1, use of steroids prior to treatment, metastasis site, and laboratory data. Results A total of 205 patients were included in this study. Of those, 108 patients exhibiting complete or partial response were defined as responders. Those exhibiting progressive disease (N = 52) were defined as non-responders. In the univariate analysis, Eastern Cooperative Oncology Group performance status score ≥ 2 (p = 0.0832), stage IV disease or recurrence (p = 0.0487), PD-L1 TPS 50–89% (p = 0.0657), use of steroids prior to the administration of pembrolizumab (p = 0.0243), malignant pleural effusion (p = 0.0032), and baseline C-reactive protein (CRP) levels > 1.0 mg/dL (p = 0.0390) were significantly associated with non-response to treatment. In the multivariate analysis, use of steroids prior to the administration of pembrolizumab (odds ratio [OR]: 5.86; 95% confidence interval [CI]: 1.32–31.8; p = 0.0200), malignant pleural effusion (OR: 2.68; 95% CI: 1.15–6.35; p = 0.0228), and baseline CRP > 1.0 mg/dL (OR: 2.17; 95% CI: 1.03–4.68; p = 0.0402) were significantly associated with non-response to treatment. Conclusion In real-world patients with NSCLC and a PD-L1 TPS ≥50%, use of steroids prior to treatment, malignant pleural effusion, and baseline CRP levels > 1.0 mg/dL reduced the response of first-line monotherapy with pembrolizumab.

INTRODUCTION The anatomical variations in accessory lymphatic pathways around the axillary region may work as a drainage route for excess lymphatic fluid accumulation in secondary upper extremity lymphedema. In this report, accessory lymphatic pathways extending to the shoulder, neck, and breast regions in secondary upper extremity lymphedema patients are shown using indocyanine green (ICG) lymphography. PATIENTS AND METHODS Between January 2012 and May 2015, 30 limbs of 29 patients with upper extremity lymphedema after malignant tumor resection were evaluated. ICG lymphography was performed after chronic lymphedema formation. RESULTS Of the 30 limbs, accessory lymphatic pathways were identified across the axillary region in 3 patients using ICG lymphography. In 2 of these 3 patients, accessory drainage lymphatics were connected to the cervical lymph nodes. In regard to the distribution of dermal backflow patterns, dermal backflow appeared in 26 patients-in the forearm in 26 patients and in the upper arm in 20 patients. CONCLUSIONS Accessory lymphatic pathways are thought to be the drainage routes in the affected arm, which may prevent edema progression to the terminal stage. Variations in the lymphatic system are easily visualized using ICG lymphography. Understanding of accessory lymphatic routes in lymphedema patients may provide new insight for further understanding the pathophysiology of lymphedema.

Bright illumination sources using xenon lamps have improved microsurgical visualization under an operating microscope; however, surgeons must recognize the potential for accidental thermal damage to soft tissues.In this article, we present 2 reports of microscopic thermal burn in lymphaticovenular anastomosis (LVA).A 23-year-old woman and a 57-year-old woman with bilateral lymphedema of the legs had LVAs on both legs under local anesthesia. The burn wound in a 23-year-old woman was full thickness, and the one in a 57-year-old woman was deep dermal burn. Both of them healed without skin grafting.Working distance and high illumination intensity are important risk factor. The use of epinephrine as part the local anesthetic mixture that decreases blood flow is also a major risk factor for thermal burns. Lymphaticovenular anastomosis particularly requires high magnification, which leads to increasing the intensity and decreasing the working distance. The surgical conditions around LVA are inherently prone to microscope-induced thermal burns.

Delayed wound healing in lymphedema is assumed to be caused by two reasons, pathophysiological and immunological effects of lymphedema. The aim of this review is to establish how impaired lymphatics alter wound healing pathophysiologically and immunologically, and to propose treatment modalities that can promote wound healing in lymphedema. Lymphaticovenular anastomoses (lymphovenous anastomoses [LVAs]) were performed on patients who had recurrent cellulitis several times with lymphorrhea and developed severe ulcers that were refractory to skin grafts, flaps, and conservative therapy. The lymphorrhea and the ulcer had healed by 4 weeks. Moreover, the lymphedema improved without compression therapy. Lymphedema is characterized pathophysiologically by localized peripheral edema that compresses the microvasculature and lymphatic vasculature and impairs tissue remodeling. Another suspected mechanism is an imbalance in the differentiation of participating immune cells. Profound suppression of T helper (Th)1 cells is likely to increase the risk of infection, and excessive differentiation of Th2 cells, including M2 macrophage polarization, may promote fibrosis, which disrupts the carefully orchestrated wound healing process. Although negative-pressure wound therapy is useful for the treatment of delayed wound healing in lymphedema, LVAs may be necessary to treat the fundamental problem of lymphedema. LVAs are considered to create a bypass to the lymph nodes through which dendritic cells (DCs) can transmit antigen information to T cells. LVAs are considered to neutralize chronic inflammation by allowing more DCs to return into the circulation, thereby improving wound healing.

The authors describe 3 cases with successful fingertip replantations using supermicrosurgical arteriole (terminal branch of digital artery) anastomoses, arteriole graft obtained from the same fingertip defect, reverse arteriole flow to subdermal venule, and delayed venular drainage for venous congestion. Among these 16 consecutive distal phalangeal replantations, 7 fingers showed postoperative venous congestion (43.8% of the total fingers) and 5 were reoperated on with delayed venous drainage under digital block. All the reoperated fingers were successfully drained by additional single or double venous drainage with a vein graft (100% success rate). As a result, 13 fingers survived (81.3% success rate).

The authors proposed a new less invasive island flap, namely the first metatarsal artery capillary perforator flap. The advantages of this flap include the preservation of the first metatarsal artery and the adiposal tissue in the web space, thereby preventing compression around the remaining deep peroneal nerve.

Prof. Koushima, president of World Society for Reconstructive Microsurgery, proposes an innovative concept and technique of the multi-stage ‘Orochi’ combined flaps (sequential flaps in parallel). The technique opens a new vista in reconstructive microsurgery.

ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells.

The thoracodorsal artery perforator flap with capillary perforators (TAPcp) is based on capillary perforators arising from the descending branch of the thoracodorsal artery and can overcome the drawbacks of the conventional TAP flap, which results in anatomical variations due to the presence of a dominant muscle or septocutaneous perforators. We applied color Doppler ultrasonography (US) to preoperatively visualize capillary perforators of the descending branch of thoracodorsal artery to facilitate successful flap elevation.Using preoperative color Doppler US, we examined seven flaps in seven patients who had undergone reconstruction with TAPcp flaps between January 2014 and April 2015. Capillary perforators with diameters0.5 mm were identified in the anterior border of the latissimus dorsi (LD) muscle. Perforator courses and their penetration points were marked to guide dissection.All seven TAPcp flaps were successfully harvested without pedicle damage or perfusion disorders. No serious postoperative complications occurred such as total necrosis or absorption of the transferred adipose flap. In all seven cases, capillary perforators and the descending branch of the thoracodorsal artery were found almost exactly where the preoperative color Doppler US was targeted.Using the technique described herein, capillary perforators of the descending branch of the thoracodorsal artery are easily visualized, and TAPcp flaps can be easily used for various kinds of reconstruction. Moreover, this technique is quick and safe to administer.

Summary Background As a clinical evaluation of secondary lymphedema of the leg, indocyanine green (ICG) lymphographic assessment has established its usefulness. In this study, we analyzed the ICG findings of patients with secondary lymphedema of the leg, focusing on the location and spreading pattern of dermal backflow (DBF). Methods Between April 2013 and June 2015, we investigated ICG findings performed on 90 patients with secondary lymphedema of the leg following malignant cancer resection. The patients comprised 88 women and two men; ICG lymphography was performed 12–24 h after the injection. Results Of the 90 patients, ICG lymphographic DBF was evident in 64 from the proximal region of the leg, termed as the proximal pattern. Of the 90 patients, DBF was found to appear in 18 patients mainly in the distal part of the leg, termed as the distal pattern. Conclusions In the proximal pattern, the ICG injected into the distal part of the leg propelled to the proximal part, but an obstruction after lymphadenectomy caused ICG pooling to appear first on the proximal side. In the distal pattern, the lymphatic system hypoplasia of the leg may have already been present, and lymph node dissection might be the only trigger for the development of lymphedema. This classification may reflect the pumping function and preexisting hypoplasty of the lymphatic vessels, and provides a novel approach for the pathological evaluation of lymphedema. Patients with proximal pattern on ICG lymphography may well indicate lymphaticovenous anastomosis.

Summary:. Syndactyly of the hand is commonly treated using local flaps with skin grafts; however, contractures and/or pigmentation pose a challenge, requiring repeated surgery. Here, we describe a case of a 1-year-old boy who underwent web transplantation for syndactyly. To the best of our knowledge, no “web for web” transplantations have been documented in pediatric literature. Because the patient had an “extra” web space, functional and aesthetic reconstruction was performed with careful preparation. The vascular pattern was assessed using high-resolution ultrasonography. The flap was harvested under a microscope, intravascular stenting was performed for secure anastomosis, and the adequacy of circulation in the flap was verified using the indocyanine green test. Each technique in the procedure used by us contributed to making the microsurgery safer. The present case suggests that “web for web” is a favorable treatment option for some cases, although these would be limited in number.

Supplemental Digital Content is available in the text., Summary: One of the primary goals of penile reconstruction for female-to-male transsexuals is to enable voiding while standing. Metoidioplasty represents a viable option, but it is associated with a high rate of postoperative fistula formation and recurrence, which affects the aesthetic and functional outcomes. Subsequent surgical repair using scarred and inadequate local tissue may contribute to fistula recurrence. The folded superficial circumflex iliac artery perforator (SCIP) island flap offers sufficient well-vascularized tissue and skin envelope for the reconstruction of the urethra and outer skin after failed metoidioplasty. The SCIP flap can be elevated as a hairless thin flap, making it useful in urethral reconstruction even when it is folded. We describe a case of a 44-year-old female-to-male transsexual patient who developed a refractory urethrocutaneous fistula after metoidioplasty. Surgical repairs were attempted using local tissue 4 times without success. The patient presented to our hospital, and we performed urethral reconstruction using a folded, pedicled SCIP flap for both urethra and skin augmentation. The postoperative course was uneventful, with satisfactory functional results and low donor-site morbidity. No fistula recurrence was observed during the 2 years of follow-up. This novel procedure offers a viable alternative technique for refractory urethrocutaneous fistula repair.

Despite advances in supermicrosurgical techniques, the ability to anastomose vessels with a diameter of less than 0.2 mm remains limited. One of the reasons for this limitation is that the dilation methods currently available, such as inserting the tip of a microforceps into the lumen or topical application of a vasodilator such as papaverine hydrochloride or xylocaine spray, are not effective in very small vessels. To overcome this problem, we have developed a method whereby nylon monofilaments are placed inside the vessel lumen to act as a dilator. Using this method, a smaller nylon monofilament is inserted into the vessel as a guide before inserting a larger nylon monofilament as a dilator. After the smaller guide monofilament has been inserted, it is then much easier to insert another monofilament for dilation, even if it is a larger one. Using this method, even a vessel with a diameter of less than 0.1 mm could be dilated to greater than 0.2 mm. The dilator monofilament can also be used as an intravascular stent in the anastomosis. We have found that anastomosis of vessels with a diameter of less than 0.1 mm is possible using this method. In our experience, the immediate patency rate has been 100%. We believe mechanical dilation with a nylon monofilament is helpful for supermicrosurgery and even ultramicrosurgery.

Background Recently, a superthin "pure skin perforator" flap without any subcutaneous tissue was proposed, but the vascularity is still unclear. The authors therefore investigated the vascularity of the proposed superficial circumflex iliac artery-pure skin perforator along with its clinical applications and findings on indocyanine green imaging. Methods The locations and dimension of 70 pure skin perforators on 40 flaps were investigated and classified into central-peripheral and mediolateral parts. Indocyanine green angiography was used to analyze the patterns of the vascular anatomy. Results Twenty-seven of 29 cases (93.1 percent) presented with pure skin perforator vessels within the area 5 cm above and 1 cm below the inguinal ligament and 4 cm medial and 2 cm lateral from the anterior superior iliac spine. The total flap size averaged 39 ± 22 cm(2) (range, 3 to 90 cm(2)). A subanalysis of the relationship between the flap size and location of pure skin perforators within the single, double, and triple pure skin perforator flap subgroups did not reveal any significance. Indocyanine green angiography revealed three interesting perfusion patterns of pure skin perforator flap: a radial diffusion pattern, direct linking vessels in the intradermal layer, and intradermal arteriovenous shunts. Conclusions The location number of the pure skin perforators within the flap was not considered to be a crucial factor in the flap design and size in this study. This new knowledge regarding the pure skin perforator concept will allow surgeons to elevate a full-thickness skin flap safely.

Ciguatoxins are polyether marine toxins that act as sodium channel activators. These toxins cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents several symptoms in humans including long-term neurological alterations. Earlier work has shown that both acute and chronic exposure of primary cortical neurons to synthetic ciguatoxin CTX3C have profound impacts on neuronal function. Thus, the present work aimed to identify relevant neuronal genes and metabolic pathways that could be altered by ciguatoxin exposure. To study the effect of ciguatoxins in primary neurons in culture, we performed a transcriptomic analysis using whole mouse genome microarrays, for primary cortical neurons exposed during 6, 24, or 72 h in culture to CTX3C. Here, we have shown that the effects of the toxin on gene expression differ with the exposure time. The results presented here have identified several relevant genes and pathways related to the effect of ciguatoxins on neurons and may assist in future research or even treatment of ciguatera. Moreover, we demonstrated that the effects of the toxin on gene expression were exclusively consequential of its action as a voltage-gated sodium channel activator, since all the effects of CTX3C were avoided by preincubation of the neurons with the sodium channel blocker tetrodotoxin The research leading to these results has received funding from the following FEDER cofounded-grants. From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, AGL2014-58210-R, AGL2016-78728-R (AEI/FEDER, UE), ISCIII/PI16/01830 and RTC-2016-5507-2. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD and ITC-20161072. From European Union POCTEP 0161-Nanoeaters -1-E-1, and Interreg AlertoxNet EAPA-317-2016. ABJ is recipient of a predoctoral fellowship from the Spanish Ministry of Education SI

This case report demonstrates an important supermicrosurgical technique for lymphedema, which was established by Isao Koshima in 1994. So far, over 2,000 cases of limb edema have been treated by this surgical method.

Avermectins were isolated as compounds possessing anthelmintic activity from the culture broth of Streptomycesavermitilis by Ōmura and co-workers. Owing to their potent anthelmintic and insecticidal activities, as well as their unique pentacyclic architecture, the avermectin family attracted keen interest from synthetic organic chemists. We have recently completed a more efficient and straightforward total synthesis of avermectin B1a, as compared with previous syntheses.

Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer’s diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined. We examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 −/− mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 −/− mice. In humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 −/− and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 −/− mice. Aldh2 −/− tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 −/− mice than in WT mice. ALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a “premature lung aging” effect.

Heat-induced antigen retrieval (HIAR) is an essential technique for current immunohistochemistry. We describe the mechanisms of HIAR and its protocols for formalin-fixed, paraffin-embedded specimens and frozen sections, which are the most popular materials for immunohistochemistry using light microscopy. In addition, we describe the antigen retrieval method for highly masked epitopes and double immunostaining using the horseradish peroxidase (HRP)-labeled antibody method and immunofluorescence method in this chapter.

The cyanosporasides A-F are a collection of monochlorinated benzenoid derivatives isolated from the marine actinomycetes Salinispora and Streptomyces sp. All derivatives feature one of two types of cyanocyclopenta[a]indene frameworks, which are regioisomeric in the position of a single chlorine atom. It is proposed that these chloro-substituted benzenoids are formed biosynthetically through the cycloaromatization of a bicyclic nine-membered enediyne precursor. Herein, we report the synthesis of such a bicyclic precursor, its spontaneous transannulation into a p-benzyne, and its differential 1,4 hydrochlorination reactivity under either organochlorine or chloride-salt conditions. Our bioinspired approach culminated in the first regiodivergent total synthesis of the aglycons A/F and B/C, as well as cyanosporasides D and E. In addition, empirical insights into the site selectivity of a natural-like p-benzyne, calculated to be a ground-state triplet diradical, to hydrogen, chlorine, and chloride sources are revealed.