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Background Mesenchymal stem cells or their conditioned medium improve chronic wound healing, and their effect is enhanced by hypoxia. Diabetic foot ulcers are chronic wounds characterized by abnormal and delayed healing, which frequently require amputation. The authors evaluated the effect of topical application of conditioned medium from hypoxically cultured amnion-derived mesenchymal stem cells on wound healing in diabetic mice. Methods Amnion-derived mesenchymal stem cells were cultured under 21% oxygen to prepare normoxic conditioned medium and under 1% oxygen to prepare hypoxic conditioned medium. Hydrogels containing standard medium, normoxic conditioned medium, or hypoxic conditioned medium were topically applied to excisional wounds of mice with streptozotocin-induced diabetes. Ulcer tissues were harvested on day 9; immunohistochemical and quantitative polymerase chain reaction analyses were performed to analyze angiogenesis, inflammatory cell infiltration, and expression levels of inflammation-related genes. Results Hypoxic conditioned medium significantly enhanced wound closure, increased capillary density and epithelization, and reduced macrophage infiltration. It also tended to reduce the infiltration of neutrophils and enhance the infiltration of regulatory T cells; it showed a tendency to downregulate the expression of the inflammation-related genes interleukin-1β, interleukin-6, chemokine ligand 1, and chemokine ligand 2. Normoxic conditioned medium exhibited similar effects, although they were of lesser magnitude than those of hypoxic conditioned medium. Conclusions Hydrogels containing hypoxically cultured, amnion-derived mesenchymal stem cell conditioned medium accelerated wound healing in diabetic mice by enhancing angiogenesis, accelerating epithelization, and suppressing inflammation. Therefore, topical application of amnion mesenchymal stem cell-derived hypoxic conditioned medium could be a novel treatment for diabetic foot ulcers.

Lymphocutaneous fistula after lymph node dissection is intractable, yet there is no established treatment strategy. This study demonstrates the wound closure time achieved by a new method of combined internal and external negative pressure wound therapy (CIEN) in patients with lymphocutaneous fistula. The subjects of this study were six consecutive patients with lymphocutaneous fistula after lymphatic surgery, who were treated with CIEN between 2018 and 2020. The CIEN technique can be summarized as follows: first, internal foam is inserted into the fistula from the opening of the fenestration. Next, a slightly larger area of external foam is applied above the fistula flap outside the external margin of the foam-filled fistula. After bridging the internal foam and external foam, negative-pressure wound therapy is carried out on this bridging foam block. CIEN led to rapid and complete wound healing in all six patients. Fistula flap margin ischemia developed in one patient, but adjusting the mode and pressure settings resulted in improvement. Three patients suffered contact dermatitis. There were no signs of tumor or fistula recurrence in any patients after at least 3 months of follow-up. CIEN is an effective and less invasive treatment modality than the conventional method of managing lymphocutaneous fistula.

We report a case of third-degree burn involving 5% of the total body surface area caused by off-label use of Hanautherm®, an infrared radiant heat lamp for bed-warming, in a patient with severe accidental hypothermia. This iatrogenic burn required repeated surgical interventions and long-term hospitalization and caused subsequent cosmetic disfigurement and functional disability. To our knowledge, this is the first reported adult case of iatrogenic burn occurring during treatment for hypothermia. Radiant heat lamps should never be used for rewarming of patients with hypothermia without careful observation.

Objective: In critical limb ischaemia (CLI), first-line therapy is revascularisation, but alternative treatment options are needed in certain cases. Maggot debridement therapy (MDT) is historically considered to be contraindicated in ischaemic ulcers. Wound care in patients with CLI is becoming increasingly diverse with the development of novel revascularisation strategies; therefore, CLI now needs to be reconsidered as an indication for MDT. Method: We retrospectively reviewed five legs with CLI (five male, one female) treated with MDT between January 2013 and December 2017. Changes in skin perfusion pressure (SPP) around the ulcer before and after MDT were evaluated. One or two cycles of MDT were performed (eight in total). We also evaluated the proportion of necrotic tissue in the ulcer and the presence of exposed necrotic bone. The proportion of necrotic tissue in the ulcer was classified as NT 1+ (75%). Results: When the proportion of necrotic tissue was >50%, with no exposed necrotic bone in the wound, an increase in SPP was observed after five (62.5%) of eight cycles of MDT. And with a proportion of necrotic tissue of Conclusion: Effective MDT with increased SPP requires an ulcerative state of necrotic tissue grade > NT 3+, with no exposed necrotic bone.

Background The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large-scale Asian studies that include follow-up data have been reported. Objectives To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease-specific survival in patients with invasive melanoma. Results In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5-year disease-specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions Our study revealed the characteristics of melanoma in the Japanese population. The 5-year disease-specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

Background and objectives Vascularized lymph node transfer (LNT) is gaining popularity in the treatment of lymphedema. However, it is unclear whether the vascularization of transferred lymph nodes (LNs) contributes to functional improvement. High endothelial venules (HEVs) are specialized vessels that allow lymphocytes to enter LNs. In this study, we compared the numbers of HEVs and lymphocytes in LNs after vascularized and nonvascularized LNT. Methods Fifty mice were divided into three groups (group 1, pedicled vascularized LNT; group 2, pedicled nonvascularized LNT; group 3, free nonvascularized LNT). Afferent lymphatic reconnection was confirmed by patent blue staining. The transferred LNs were harvested 4 weeks after surgery. HEVs, B-cells, and T-cells were subjected to immunohistochemical staining and quantified. Results Afferent lymphatic reconnection was observed in 13 of 20 transferred LNs in group 1, 11 of 15 in group 2, and 7 of 15 in group 3. The ratio of dilated/total HEVs in transferred LNs with afferent lymphatic reconnection was significantly higher in group 1 than in groups 2 and 3. No significant differences in numbers of B-cells and T-cells were found in the transferred LNs. Conclusions We found that more functional HEVs were preserved in cases with successful afferent lymphatic reconnection after vascularized LNT than after nonvascularized LNT.

The timing of cleft lip nose surgery remains controversial. The less invasive the procedure at the time of primary cleft lip repair, the less the growth and development of the nose is affected. Therefore, the nasal-stenting component of presurgical nasoalveolar molding has increasingly been used. However, not all cleft centers use such treatment. Conventional postsurgical placement of silicone nasal retainers remains popular. No report has yet compared presurgical nasal stenting (preNS) and postsurgical nasal retainer placement (postNR). In this study, postoperative nasal form outcomes after primary lip repair using preNS or postNR in patients with complete unilateral cleft lips, alveoli, and palates were compared. Patients in whom preNS alone was used for 6 months (group I) were compared with those receiving postNR (no preNS) for 6 months after primary nasal cartilage dissection (group II) and controls with no appliance (group III). Nasal anthropometric distances and angular relationships were measured photographically to assess nasal symmetry at 4 years of age in all groups. Compared to group III, groups I and II exhibited significantly greater nostril heights (P = 0.0075, P = 0.0015 respectively) and columellar deviation angles (P = 0.0020, P = 0.0221). Groups I and II did not differ significantly. No significant between-treatment difference in terms of nasal symmetry between preNS and postNR was observed. However, both treatments afforded significantly better results than no treatment. Since older infants tend to resist the placement of nasal devices, preNS is more feasible in this age group.

Aim: To study the characteristics and surgical treatment of inguinal endometriosis (IEM), which can occur in women of reproductive age. Methods: Patients who underwent groin surgery at the Hiroshima City Funairi Citizens Hospital between 2004 and 2017 were retrospectively examined. Patients with IEM were divided into 3 groups based on the site of occurrence as follows: at a hernia sac or hydrocele of Nuck’s canal (type I), round ligament (type II), or subcutaneous area (type III). Clinical characteristics were compared among groups. Results: Of 2,798 patients investigated, 28 were pathologically diagnosed as having IEM with 15, 10, and 3 classified as type I, II, and III respectively. All patients presented with a mass (median 20 mm) and/or bulge that mainly occurred at the right inguinal region. Sixteen patients presented with inguinal pain associated with menstruation. While the groups did not differ in terms of most clinical characteristics, the lack of a preoperative diagnosis of IEM occurred more frequently for type I than for types II and III. Conclusions: Because IEM-type I might be underdiagnosed preoperatively, complete resection of a hernia sac or hydrocele of Nuck’s canal with subsequent pathological examination is required for women of reproductive age with an inguinal disease.

Lymph node (LN) transplantation is a recognized method for reconstruction of the lymphatic system and is used in the clinical setting to treat lymphedema. However, it is unclear whether transplanted LNs contribute to immune surveillance. In our study, we investigated whether a single transplanted non-vascularized LN, defined as a tumor-draining transplanted lymph node (TDTLN), could exert an immune-mediated antitumor effect. LN and lung metastases and primary tumor enlargement were evaluated in mice that were inoculated with B16-F10-luc2 melanoma cells in a hind limb footpad without (group 1) and with (group 2) popliteal lymph node (PLN) resection and in mice that underwent LN transplantation after PLN resection (group 3). The function of a TDTLN (group 3) and a tumor-draining popliteal lymph node (TDPLN; group 1) was evaluated in the context of cancer. LN and lung metastases were significantly aggravated by PLN resection but were significantly decreased by LN transplantation. Immunohistochemistry showed that the TDTLNs retained T-cells and B-cells and fluorescence-activated cell sorting analysis confirmed expansion of lymphocytes in these nodes; however, the degree of expansion in TDTLNs was different from that in TDPLNs. Expression of cytokines associated with immunostimulation was confirmed in the TDTLNs as well as in the TDPLNs. One of the differences in the immune-mediated antitumor effect of the TDPLNs and TDTLNs was ascribed to a difference in the site of lymphocyte homing to peripheral LNs through high endothelial venules. Non-vascularized LN transplantation had an immune-mediated antitumor effect.

Lymph node transplantation is being increasingly recognized as a method of reconstruction of the lymphatic system for the treatment of lymphedema. However, the mechanisms regulating the connections between the lymphatic vessels and the lymph nodes remain poorly understood. The objective of this study was to examine whether removal of a popliteal lymph node (PLN) could result in rerouting of lymph flow and whether a single transplanted nonvascularized lymph node could reconnect with a lymphatic vessel and restore lymph flow.Thirty-six mice were allocated to undergo resection of a PLN alone (group 1) or a transplanted lymph node after resection of a PLN (group 2). Changes in lymph flow were observed using indocyanine green dye. The ability of the transplanted lymph node to reconnect with the lymphatic vessels was examined by fluorescein isothiocyanate (FITC)-dextran and immunohistochemical staining. In group 1, the flow of lymph was redirected to an inguinal lymph node (ILN) in 8 of 18 mice and continued to drain to the PLN in 10 mice. In group 2, the lymph continued to drain normally after removal of the PLN, and was also directed to an ILN in two mice. FITC-dextran demonstrated continuity of the transplanted PLN and the lymphatic vessels. Immunohistochemical staining showed that T cell and B cell populations in the transplanted lymph node were preserved.Lymphatic flow was rerouted after lymph node resection. A transplanted lymph node can be made viable with normal lymph flow by reconnecting the transplanted lymph node to a lymphatic vessel.

Mesenchymal stem cells are a valuable cell source in regenerative medicine, and conditioned medium obtained from mesenchymal stem cells reportedly inhibits inflammation. Keloids are characterized by abnormal fibrosis, caused by fibroblasts in response to inflammation. In this study, the authors evaluated whether conditioned medium obtained from amnion-derived mesenchymal stem cells suppressed activation of keloid fibroblasts.Keloid (n = 7), mature (n = 5), and normal (n = 5) fibroblasts were harvested from patients. Fibroblasts were stimulated with transforming growth factor (TGF)-β, and the effects of conditioned medium obtained from amnion-derived mesenchymal stem cells on cell proliferation, activation, and expression of extracellular matrix-related genes were analyzed. The effect of concentrating the conditioned medium by ultrafiltration on fibroblast activation was also analyzed.Conditioned medium obtained from amnion-derived mesenchymal stem cells significantly up-regulated proliferation of mature fibroblasts but tended to suppress that of keloid fibroblasts. Conditioned medium obtained from amnion-derived mesenchymal stem cells significantly suppressed the TGF-β-induced up-regulation of α-smooth muscle actin in keloid and normal fibroblasts and collagen I in keloid fibroblasts, but not in mature fibroblasts. The conditioned medium obtained from amnion-derived mesenchymal stem cells concentrated by ultrafiltration and the filtrate significantly suppressed TGF-β-induced α-smooth muscle actin expression.Conditioned medium obtained from amnion-derived mesenchymal stem cells prevents proliferation and activation of keloid fibroblasts and is a promising keloid treatment for administration as a topical agent.Therapeutic, V.

Oculo-auriculo-fronto-nasal syndrome (OAFNS) is a rare anomaly characterized by features overlapping those of frontonasal dysplasia (FND) and the oculo-auriculo-vertebral spectrum (OAVS). The FND features malformation of frontonasal process-derived structures, characterized by anomalies in the central portion of the face. The OAVS is characterized by developmental anomalies of the first and second pharyngeal arches. The OAFNS is a condition with clinical features of both FND and OAVS.Here, the authors present the case of a male with OAFNS who not only exhibited typical OAFNS symptoms but also a dysplastic bony structure that bridged the anterior nasal spine and inferior nasal bones, and unilateral type 3 Duane retraction syndrome (absence of right-eye abduction). Abnormal nasal bones are characteristic of OAFNS; such abnormalities are absent from FND and OAVS. The authors reduced the dysplastic nasal bony structure via open external rhinoplasty, followed by lateral nasal osteotomy when he was 16 years of age. The nasal dorsum appeared natural after surgery and he was satisfied with the result.

Piperacillin-tazobactam (PIP-TAZ) is commonly used to treat intraabdominal infections; however, its penetration into abdominal sites is unclear. A pharmacokinetic analysis of plasma, peritoneal fluid, and peritoneum drug concentrations was conducted to simulate dosing regimens needed to attain the pharmacodynamic target in abdominal sites. PIP-TAZ (4 g-0.5 g) was intravenously administered to 10 patients before abdominal surgery for inflammatory bowel disease. Blood, peritoneal fluid, and peritoneum samples were obtained at the end of infusion (0.5 h) and up to 4 h thereafter. PIP and TAZ concentrations were measured, both noncompartmental and compartmental pharmacokinetic parameters were estimated, and a simulation was conducted to evaluate site-specific pharmacodynamic target attainment. The mean peritoneal fluid:plasma ratios in the area under the drug concentration-time curve (AUC) were 0.75 for PIP and 0.79 for TAZ, and the mean peritoneal fluid:plasma ratios in the AUC were 0.49 for PIP and 0.53 for TAZ. The mean PIP:TAZ ratio was 8.1 at both peritoneal sites. The regimens that achieved a bactericidal effect with PIP (time above minimum inhibitory concentration [MIC] >50%) at both peritoneal sites were PIP-TAZ 4.5 g twice daily for an MIC of 8 mg/L, as well as 4.5 g three times daily, and 3.375 g four times daily for an MIC of 16 mg/L. These findings clarify the peritoneal pharmacokinetics of PIP-TAZ, and help consider the dosing regimens for intraabdominal infections based on site-specific pharmacodynamic target attainment.

Early excision and skin grafting is the principle treatment for a burned hand although there are occasions when it cannot be done such as severe general condition, delayed consultation, and the lack of a definitive assessment of burn depth. This study analyzes the factors that affected function after a delayed excision and skin graft for hands with a deep dermal burn. This study retrospectively evaluated 43 burned hands that required a delayed excision and split-thickness skin graft on the dorsal side. Cases were required to only have split-thickness skin grafting from the dorsum of the hand and fingers distally to at least the proximal interphalangeal joint at least 8 days after the injury. The hands were divided into two functional categories: Functional category A, normal or nearly normal joint movements, and functional category B, abnormal joint movements. Demographic data were assessed statistically by a univariate analysis following a multiple regression analysis by a stepwise selection. A significant difference was observed between the groups in the number of days from grafting to complete wound healing of the graft site and with or without an escharotomy in the analysis. These parameters were statistically significant predictors of functional category B. The functional outcome of a burned hand after a delayed excision and split-thickness skin graft on the dorsal side became degraded depending on the number of days from grafting to complete wound healing. Cases that underwent an escharotomy also showed deterioration in function.

We report a case of locally advanced rectal cancer presenting with perforation that was successfully resected after preoperative chemotherapy. A 66-year-old woman visited our emergency room complaining of lower abdominal pain. Abdominal CT showed a rectal tumor with fluid collection and free air in the pelvis. The patient was diagnosed with panperitonitis secondary to cancerous perforation and underwent sigmoid colostomy. A biopsy specimen of the rectal tumor showed well-differentiated tubular adenocarcinoma and wild-type RAS. After 8 courses of mFOLFOX6 plus panitumumab, the tumor shrank remarkably, and radical surgery(low anterior resection with D3 lymph node dissection)was performed. Microscopic examination of the resected specimen showed that almost half of the tumor cells were replaced by histiocytes and necrotic tissue. Preoperative chemotherapy with panitumumab may be an effective treatment for RAS wild-type locally advanced colon cancer, even if the primary tumor develops perforation.

There has been a long-standing need for guidelines on the diagnosis and treatment of keloids and hypertrophic scars that are based on an understanding of the pathomechanisms that underlie these skin fibrotic diseases. This is particularly true for clinicians who deal with Asian and African patients because these ethnicities are highly prone to these diseases. By contrast, Caucasians are less likely to develop keloids and hypertrophic scars, and if they do, the scars tend not to be severe. This ethnic disparity also means that countries vary in terms of their differential diagnostic algorithms. The lack of clear treatment guidelines also means that primary care physicians are currently applying a hotchpotch of treatments, with uneven outcomes. To overcome these issues, the Japan Scar Workshop (JSW) has created a tool that allows clinicians to objectively diagnose and distinguish between keloids, hypertrophic scars, and mature scars. This tool is called the JSW Scar Scale (JSS) and it involves scoring the risk factors of the individual patients and the affected areas. The tool is simple and easy to use. As a result, even physicians who are not accustomed to keloids and hypertrophic scars can easily diagnose them and judge their severity. The JSW has also established a committee that, in cooperation with outside experts in various fields, has prepared a Consensus Document on keloid and hypertrophic scar treatment guidelines. These guidelines are simple and will allow even inexperienced clinicians to choose the most appropriate treatment strategy. The Consensus Document is provided in this article. It describes (1) the diagnostic algorithm for pathological scars and how to differentiate them from clinically similar benign and malignant tumors, (2) the general treatment algorithms for keloids and hypertrophic scars at different medical facilities, (3) the rationale behind each treatment for keloids and hypertrophic scars, and (4) the body site-specific treatment protocols for these scars. We believe that this Consensus Document will be helpful for physicians from all over the world who treat keloids and hypertrophic scars.

Keloids can be recalcitrant, and a well-planned treatment strategy is essential. Multiple ear piercings have recently become popular, particularly among younger age groups. Management of keloids that develop after piercing of the ear cartilage may be particularly problematic. Helical rim keloids are difficult to excise because of the complex, three-dimensional, cartilaginous structure of the helix and its thin and tightly adherent covering layer of skin. The chondrocutaneous advancement flap introduced by Antia and Buch may be a useful reconstructive option for a helical rim keloid after marginal loss of a segment of the helix as a result of trauma, a burn, or excision of a malignant tumor. However, this technique is limited to wounds that involve only the helix. In this technical note, we describe the use of a chondrocutaneous bilateral advancement flap with postoperative radiation therapy to treat a more invasive and relatively large keloid on the scapha. This technique is straightforward and safe in terms of preserving the blood supply. The addition of adjuvant radiation therapy can help to decrease the risk of recurrence and preserve the morphological structure of the ear and patient satisfaction.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 .

Purpose Vascularized lymph node transfer is becoming more common in the treatment of lymphedema, but suitable small animal models for research are lacking. Here, we evaluated the feasibility of pedicled vascularized inguinal lymph node transfer in mice. Methods Twenty-five mice were used in the study. An inguinal lymph node-bearing flap with a vascular pedicle containing the superficial caudal epigastric vessels was transferred into the ipsilateral popliteal fossa after excision of the popliteal lymph node. Indocyanine green (ICG) angiography was used to confirm vascularity of the flap. ICG lymphography was performed to evaluate lymphatic flow at 3 and 4 weeks postoperatively. Patent blue dye was injected into the ipsilateral hind paw to observe staining of the transferred lymph node at 4 weeks postoperatively. All transferred lymph nodes were then harvested and histologically evaluated by hematoxylin and eosin staining. Results In 16 of the 25 mice, ICG lymphography showed reconnection between the transferred lymph node and the afferent lymphatic vessels, as confirmed by patent blue staining. Histologically, these transferred lymph nodes with afferent lymphatic reconnection significantly regressed in size (0.37 ± 0.24 mm2 ) and showed clear follicle formation, whereas those without afferent lymphatic reconnection showed less size regression (1.31 ± 1.17 mm2 ); the cell population was too dense to allow identification of follicles. Conclusions We established a mouse model of vascularized lymph node transfer with predictable afferent lymphatic reconnection. Both the vascularization and reconnection might be necessary for functional regeneration of the transferred lymph node.

Keloids mark a chronic inflammatory disease characterized by a fibroproliferative disorder of the skin. A genome-wide association study showed that single-nucleotide polymorphism rs8032158 in the neural precursor cell-expressed NEDD4 gene, which has six protein-coding transcript variants (TVs), is genetically linked to keloids. Here, we show that the high frequency of risk allele C in rs8032158 in keloid patients is associated with a selectively higher expression of TV3 of NEDD4 to activate the NF-κB pathway. Comparisons of keloid scars with normal skin samples that do not have the single-nucleotide polymorphism allele and were derived from different anatomical sites showed stronger expressions of NEDD4 TV3 and activated forms of NF-κB and STAT3 in keloid scars. Forced expression or selective knockdown of NEDD4 TV3 increased or decreased NF-κB activation in vitro. Furthermore, NEDD4 knockdown suppressed NF-κB–dependent inflammation development in vivo. Mechanistic analysis showed that NEDD4 TV3 is involved in NF-κB activation through its association with the adaptor protein RIP. These results suggest that NEDD4 TV3 is a potential diagnostic marker and therapeutic target for chronic skin diseases, including keloid.

Tessier cleft types 3 and 4 are both rare craniofacial anomalies. Here we present the first case of a girl born with a combined anomaly of Tessier clefts 3 and 4 with severe bilateral cleft lip, a displaced premaxilla, and three-dimensional underdevelopment of the hard and soft tissues of the maxilla and zygoma. This type of rare facial cleft poses a major operative challenge. Over a period of years, presurgical alveolar molding with an active appliance was followed by seven operations. A satisfactory esthetic outcome was obtained. A multidisciplinary approach to treatment with a plastic surgeon in charge of the operations and an orthodontist in charge of the cleft deformity is essential.

Lymph node (LN) transplantation is a recognized method for reconstruction of the lymphatic system and is used in the clinical setting to treat lymphedema. However, it is unclear whether transplanted LNs contribute to immune surveillance. In our study, we investigated whether a single transplanted non-vascularized LN, defined as a tumor-draining transplanted lymph node (TDTLN), could exert an immune-mediated antitumor effect. LN and lung metastases and primary tumor enlargement were evaluated in mice that were inoculated with B16-F10-luc2 melanoma cells in a hind limb footpad without (group 1) and with (group 2) popliteal lymph node (PLN) resection and in mice that underwent LN transplantation after PLN resection (group 3). The function of a TDTLN (group 3) and a tumor-draining popliteal lymph node (TDPLN; group 1) was evaluated in the context of cancer. LN and lung metastases were significantly aggravated by PLN resection but were significantly decreased by LN transplantation. Immunohistochemistry showed that the TDTLNs retained T-cells and B-cells and fluorescence-activated cell sorting analysis confirmed expansion of lymphocytes in these nodes; however, the degree of expansion in TDTLNs was different from that in TDPLNs. Expression of cytokines associated with immunostimulation was confirmed in the TDTLNs as well as in the TDPLNs. One of the differences in the immune-mediated antitumor effect of the TDPLNs and TDTLNs was ascribed to a difference in the site of lymphocyte homing to peripheral LNs through high endothelial venules. Non-vascularized LN transplantation had an immune-mediated antitumor effect.

Full-thickness defects of the entire nasal ala, including the rim, can be challenging to reconstruct. A forehead flap may provide a more imperceptible and natural-appearing reconstructed nasal ala. Previously, many authors have insisted adding cartilaginous infrastructural support for an entire, full-thickness defect to keep the postoperative alar structure symmetrical. They finally use a forehead flap after thinning of the distal covering portion subcutaneously, possibly for a Caucasian-type nasal ala. However, Asian skin has a thicker and more compact dermis than that of Caucasian skin, and the Asian ala is rounder and thicker. There may be another approach for an Asian-type nasal ala. The authors propose the possibility of nasal alar reconstruction for an entire, full-thickness defect in Asians using a forehead flap without structural support. Six patients with entire full-thickness nasal alar defects treated with full-thickness forehead flaps above the periosteum without structural support were reviewed. Five patients demonstrated esthetically good to excellent outcomes in color, texture, and symmetry. Their nasal linings were reconstructed using mucoperiosteal flaps or mucosal grafts. One patient treated with a nasal lining using a local flap showed a fair result esthetically. Asians forehead above the periosteum has adequate thickness and supportability to reconstruct the entire full-thickness nasal ala in Asians. No cartilage support is necessary.

The purpose of this study was to evaluate the superficial lymph drainage patterns of primary skin cancers of the head arising from the occipital or parietal region. The dominant patterns of lymph drainage were retrospectively reviewed in eight patients aged 36–85 years with skin cancers in the occipital or parietal region in whom sentinel lymph node biopsy or lymph node dissection had been performed at Hokkaido University Hospital between January 1981 and December 2015. Lymph drainage was mainly to the occipital (6/8, 75%), level II (5/8, 63%), and level V lymph nodes (5/8, 63%). Of the six patients with drainage to the occipital lymph nodes, four (67%) also had drainage to level V nodes. The dominant lymph drainage pattern in patients with skin cancer arising from the occipital or parietal region was to the occipital, level II, and level V lymph nodes. Further, lymph tended to drain directly from the occipital region to the level V lymph nodes.

The incidence of postoperative wound dehiscence following inguinal lymph node dissection (ILND) is higher than that in other anatomic regions. To prevent wound dehiscence, intraoperative interventions, such as trimming off the ischemic part of the flap before wound closure based on indocyanine-green (ICG) fluorescence angiography, have been introduced in our institute. This report describes a retrospective clinical study of 17 cases, and the objective of the study was to evaluate the clinical efficacy of intraoperative intervention using ICG fluorescence angiography. A total of 17 patients who underwent ILND for skin cancer between 2009 and 2013 at our institute were reviewed retrospectively, and the significance of variables, including intervention using ICG fluorescence angiography, was evaluated using Fisher’s exact test. There were nine cases of wound dehiscence, and two of these cases required a secondary skin graft. Only one case of wound dehiscence developed in the eight patients who underwent intervention based on ICG fluorescence angiography. This procedure was a significant factor influencing the risk of wound dehiscence (p = 0.003) in our study. Although this was a small case series, intraoperative intervention based on ICG fluorescence angiography was effective for preventing postoperative wound dehiscence after ILND.

The pathophysiology of secondary lymphedema remains poorly understood. This study aimed to establish a consistent mouse hindlimb lymphedema model for further investigation of the mechanism and treatment of lymphedema.The authors developed a novel postsurgical lymphedema model in the mouse hindlimb by modifying previously described methods. Lymphedema in the hindlimb was created by removing both the inguinal and popliteal lymph nodes together with the surrounding fat pads, followed by silicone splint placement in the inguinal region. Using this modified mouse model, the authors analyzed lymphatic function, histologic changes, and the expression of lymphangiogenic factors including vascular endothelial growth factor C at various time points.The splinted lymphedema model showed a significant increase of edema formation in the hindlimb compared with the sham surgery control animals. Indocyanine green lymphography revealed lymphatic drainage impairment shown by dermal backflow and rerouting of lymph flow in the lymphedema model. Histopathologic and immunohistochemical examinations showed a significant increase of skin thickness and abnormally dilated lymphatics in the lymphedema model. The expression of lymphangiogenic factors in lymphedematous tissues of the splinted lymphedema model was significantly increased compared with controls, depending on the degree of lymphedema.This splinted lymphedema model closely simulates the volume response, histopathology, and lymphography characteristics of human acquired lymphedema. Given these similarities to human lymphedema, this refinement of a mouse hindlimb model of acquired lymphedema represents a promising platform for the study of lymphatic vascular insufficiency and for the evaluation of new therapeutic modalities.

To evaluate the utility of hand-assisted laparoscopic restorative proctocolectomy (HALS-RP) compared with the conventional open procedure (OPEN-RP).Fifty-one patients who underwent restorative total proctocolectomy with rectal mucosectomy and ileal pouch anal anastomosis between January 2008 and July 2015 were retrospectively analyzed. Twenty-three patients in the HALS-RP group and twenty-four patients in the OPEN-RP group were compared. Four patients who had purely laparoscopic surgery were excluded. Restorative total proctocolectomy was performed with mucosectomy and a hand-sewn ileal-pouch-anal anastomosis. Preoperative comorbidities, intraoperative factors such as blood loss and operative time, postoperative complications, and postoperative course were compared between two groups.Patients in both groups were matched with regards to patient age, gender, and American Society of Anesthesiologists score. There were no significant differences in extent of colitis, indications for surgery, preoperative comorbidities, and preoperative medications in the two groups. The median operative time for the HALS-RP group was 369 (320-420) min, slightly longer than the OPEN-RP group at 355 (318-421) min; this was not statistically significant. Blood loss was significantly less in HALS-RP [300 (230-402) mL] compared to OPEN-RP [512 (401-1162) mL, P = 0.003]. Anastomotic leakage was noted in 3 patients in the HALS-RP group and 2 patients in the OPEN-RP group (13% vs 8.3%, NS). The rates of other postoperative complications and the length of hospital stay were not different between the two groups.HALS-RP can be performed with less blood loss and smaller skin incisions. This procedure is a feasible technique for total proctocolectomy for ulcerative colitis.

Past studies showed that integumentectomy and incontinuity could be effective procedures in the surgical management of melanoma patients. The present study reports on the historical background of these procedures. In addition, we analyze the ICG assisted integumentectomy and incontinuity techniques and algorithms that we had created when performing this procedure. In accordance with our algorithm, we performed ICG assisted integumentectomy/incontinuity procedures on 17 patients with stage III melanomas between 2008 and 2016. We also investigated the locoregional recurrence rate in a control group comprising 60 patients at stage III without using the algorithm. The former group exhibited a tendency of locoregional recurrence rate suppression. Melanoma cells in the dissected intervening tissue were microscopically identified in 2 out of 17 cases. Our ICG assisted integumentectomy or incontinuity procedures could be effective in controlling locoregional recurrence rates in melanoma cases. Moreover, our method can be generally applied because the dissection is only performed within the lymphatic pathway region identified using indocyanine green.

症例は67歳，男性．嘔気，腹部膨満を主訴に当院救急部を受診．CT検査にて十二指腸下行脚から水平脚の壁肥厚および同部位での狭窄を認めた．壁外の後腹膜には広範囲に低吸収陰影がみられた．上部消化管内視鏡検査では十二指腸粘膜の鬱血，狭窄を認めるも，明らかな腫瘍の露出は認められなかった．第８病日に十二指腸通過障害の改善，胆嚢摘除，および確定診断目的に開腹手術を施行した．手術時，術中迅速病理検査にて悪性疾患は疑われなかったため，通過障害改善の手術を行い，臓器切除は施行しなかった．病理組織学的検査にて後腹膜脂肪織炎と診断された．術後経過は良好で，術後９日目に食事を開始し，術後18日目に退院した．

症例は43歳, 女性. S状結腸癌に対してS状結腸切除, 虫垂切除を施行し, その際, 左下腹部からダグラス窩へプリーツドレーンを挿入した. 術後経過は良好で, 術後第6病日にドレーンを抜去しようとしたところ, 抜去の途中で抵抗があり, また疼痛の訴えがあったため, 抜去を断念した. その後も抵抗および疼痛の訴えのため, ドレーンを抜去することができなかった. 諸検査から, ドレーン抜去困難の原因として, ドレーン内腔への腹腔内脂肪組織の嵌入が推測された. 術後第9病日, 腹腔鏡下手術でドレーンを抜去した. 大網がドレーン側孔からドレーン内腔に嵌入していたため, 大網を引き出してドレーンを抜去した. その後, 腹腔内組織の損傷および出血の有無を十分に観察して手術を終了した. 術後経過は良好であり, 初回手術より術後第14病日に退院した. 本症例では腹腔鏡下に腹腔内の観察を十分に行うことができ, 安全にドレーンを抜去することができた.