Lymphatic drainage patterns of malignant skin tumors in the head and neck region: a single-center retrospective study.

BACKGROUND: This study aimed to clarify the relationship between primary site and lymphatic drainage pattern for malignant skin tumors in the head and neck region. Malignant melanoma and squamous cell carcinoma in the head and neck region are known to have poor prognosis because of lymph node metastasis. Nevertheless, numerous aspects of lymphatic drainage patterns remain elusive. METHODS: We statistically analyzed data of 47 patients with malignant skin tumors in the head and neck region. Information was collected on the patients' clinical characteristics, primary tumor site, and lymphatic drainage patterns. RESULTS: The parotid lymph nodes drained the greatest amount of lymph from skin tumors of the head and neck. Important lymphatic drainage pathways were the superficial cervical nodes for primary tumors in the buccal/nasal region, level IA and level IB nodes for primary tumors in the lip region, the occipital nodes, posterior auricular nodes, and level VA nodes in the parietal/occipital region, and the preauricular nodes in the auricular region. CONCLUSION: These findings have considerable significance in terms of understanding lymphatic drainage patterns for malignant skin tumors in the head and neck and may be useful for clinical decision-making and when planning treatment. Further research and clinical applications are expected to contribute to an improved prognosis in patients with cutaneous head and neck malignancies.

Type 1 Cryoglobulinemic Vasculitis Due to Monoclonal Gammopathy of Undetermined Significance Successfully Treated by Bortezomib Plus Dexamethasone.

Cryoglobulins are immunoglobulins that precipitate in cold conditions. Type I cryoglobulinemic vasculitis is associated with hematological malignancies. We herein report a case of steroid-resistant type 1 cryoglobulinemic vasculitis associated with monoclonal gammopathy of undetermined significance (MGUS) in a 47-year-old woman. By immunofixation of cryoglobulin, we found that the main component of cryoglobulin was the M protein due to MGUS, so treatment of MGUS was needed. Bortezomib+dexamethasone therapy resulted in a rapid decrease in cryoglobulin and improvement in the symptoms of cryoglobulinemic vasculitis. In refractory type I cryoglobulinemic vasculitis, treatment of the underlying gammaglobulinopathy should be considered.

Efficacy of hyperbaric oxygen after microtia reconstruction using costal cartilage: A retrospective case-control study.

Introduction: Microtia reconstruction with autologous costal cartilage framework grafting is challenging because the three-dimensional structure of the ear is highly complex, and meeting the high aesthetic demands of patients can be difficult. If the skin flap overlying the framework is thinned to achieve a smooth and accentuated outline, a poor blood supply in the thin skin flap may lead to skin necrosis, exposure of the framework, and poor surgical results. Hyperbaric oxygen (HBO2) therapy can promote the healing of complex wounds and flaps. This study sought to determine the effectiveness of HBO2 therapy for the prevention of postoperative complications after framework grafting in microtia reconstruction. Methods: We retrospectively evaluated postoperative complications and compared outcomes in pediatric patients who underwent costal cartilage grafting for microtia reconstruction at our institution between 2011 and 2015, according to whether or not they received postoperative HBO2 therapy. HBO2 therapy was applied once daily for a total of 10 sessions starting on the first postoperative day. Results: During the study period, eight patients received HBO2 therapy after costal cartilage grafting, and 12 did not. There was no significant difference in the incidence of postoperative ulcers. However, the incidence of framework exposure was lower, and the healing time was shorter in patients who received HBO2 therapy than in those who did not. Discussion: HBO2 therapy can be used safely in pediatric patients to reduce postoperative complications and improve the aesthetic outcome of microtia reconstruction. After costal cartilage grafting, HBO2 therapy should be considered as adjuvant therapy.

Intranodal lymphangiography with lipiodol as a diagnostic and therapeutic approach for spontaneous cervical chyle leak.

We present a case of spontaneous cervical chyle leak that showed as left-sided neck swelling. Spontaneous chyle leak is extremely rare. Lymphangiography with lipiodol is useful as a diagnostic and therapeutic approach for chyle leak.

Partially involuting congenital hemangioma with pyogenic granuloma-induced rapid progression following incisional biopsy in infancy: A case report.

We present a case of partially involuting congenital hemangioma (PICH) that showed rapid growth with ulceration after incisional biopsy. PICH does not typically grow after birth. However, if growth occurs due to stimuli like biopsy, it is essential to consider the possibility of pyogenic granuloma complication.

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel-Trenaunay syndrome in an Asian population : List the full names and institutional addresses for all authors.

BACKGROUND: Klippel-Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation with limb hypertrophy. KTS is thought to lie on the PIK3CA-related overgrowth spectrum, but reports are limited. PIK3CA encodes p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) that plays an essential role in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. We aimed to demonstrate the clinical utility of targeted next-generation sequencing (NGS) in identifying PIK3CA mosaicism in archival formalin-fixed paraffin-embedded (FFPE) tissues from patients with KTS. RESULTS: Participants were 9 female and 5 male patients with KTS diagnosed as capillaro-venous malformation (CVM) or capillaro-lymphatico-venous malformation (CLVM). Median age at resection was 14 years (range, 5-57 years). Median archival period before DNA extraction from FFPE tissues was 5.4 years (range, 3-7 years). NGS-based sequencing of PIK3CA achieved an amplicon mean coverage of 119,000x. PIK3CA missense mutations were found in 12 of 14 patients (85.7%; 6/8 CVM and 6/6 CLVM), with 8 patients showing the hotspot variants E542K, E545K, H1047R, and H1047L. The non-hotspot PIK3CA variants C420R, Q546K, and Q546R were identified in 4 patients. Overall, the mean variant allele frequency for identified PIK3CA variants was 6.9% (range, 1.6-17.4%). All patients with geographic capillary malformation, histopathological lymphatic malformation or macrodactyly of the foot had PIK3CA variants. No genotype-phenotype association between hotspot and non-hotspot PIK3CA variants was found. Histologically, the vessels and adipose tissues of the lesions showed phosphorylation of the proteins in the PI3K/AKT/mTOR signaling pathway, including p-AKT, p-mTOR, and p-4EBP1. CONCLUSIONS: The PI3K/AKT/mTOR pathway in mesenchymal tissues was activated in patients with KTS. Amplicon-based targeted NGS could identify low-level mosaicism from low-input DNA extracted from FFPE tissues, potentially providing a diagnostic option for personalized medicine with inhibitors of the PI3K/AKT/mTOR signaling pathway.

Systemic therapy for Asian patients with advanced BRAF V600-mutant melanoma in a real-world setting: A multi-center retrospective study in Japan (B-CHECK-RWD study).

BACKGROUND: Anti-PD-1-based immunotherapy is considered a preferred first-line treatment for advanced BRAF V600-mutant melanoma. However, a recent international multi-center study suggested that the efficacy of immunotherapy is poorer in Asian patients in the non-acral cutaneous subtype. We hypothesized that the optimal first-line treatment for Asian patients may be different. METHODS: We retrospectively collected data of Asian patients with advanced BRAF V600-mutant melanoma treated with first-line BRAF/MEK inhibitors (BRAF/MEKi), anti-PD-1 monotherapy (Anti-PD-1), and nivolumab plus ipilimumab (PD-1/CTLA-4) between 2016 and 2021 from 28 institutions in Japan. RESULTS: We identified 336 patients treated with BRAF/MEKi (n = 236), Anti-PD-1 (n = 64) and PD-1/CTLA-4 (n = 36). The median follow-up duration was 19.9 months for all patients and 28.6 months for the 184 pa tients who were alive at their last follow-up. For patients treated with BRAF/MEKi, anti-PD-1, PD-1/CTLA-4, the median ages at baseline were 62, 62, and 53 years (p = 0.03); objective response rates were 69%, 27%, and 28% (p < 0.001); median progression-free survival (PFS) was 14.7, 5.4, and 5.8 months (p = 0.003), and median overall survival (OS) was 34.6, 37.0 months, and not reached, respectively (p = 0.535). In multivariable analysis, hazard ratios (HRs) for PFS of Anti-PD-1 and PD-1/CTLA-4 compared with BRAF/MEKi were 2.30 (p < 0.001) and 1.38 (p = 0.147), and for OS, HRs were 1.37 (p = 0.111) and 0.56 (p = 0.075), respectively. In propensity-score matching, BRAF/MEKi showed a tendency for longer PFS and equivalent OS with PD-1/CTLA-4 (HRs for PD-1/CTLA-4 were 1.78 [p = 0.149]) and 1.03 [p = 0.953], respectively). For patients who received second-line treatment, BRAF/MEKi followed by PD-1/CTLA-4 showed poor survival outcomes. CONCLUSIONS: The superiority of PD-1/CTLA-4 over BRAF/MEKi appears modest in Asian patients. First-line BRAF/MEKi remains feasible, but it is difficult to salvage at progression. Ethnicity should be considered when selecting systemic therapies until personalized biomarkers are available in daily practice. Further studies are needed to establish the optimal treatment sequence for Asian patients.

Utility of Color Doppler Ultrasonography in Monitoring of a Free Jejunal Flap.

OBJECTIVES: External color Doppler ultrasonography is reported to be a useful monitoring technique that is simple and noninvasive; however, details of imaging of the transferred free jejunal flap have not been reported. We reviewed our experience using external color Doppler ultrasonography to monitor a transferred free jejunal flap and examined its utility. STUDY DESIGN: Retrospective study. METHODS: Subjects were 43 patients who underwent total pharyngolaryngectomy, reconstruction with a free jejunal flap, and color Doppler ultrasonography before, during, and after surgery between September 2017 and December 2021. RESULTS: During surgery, arterial thrombosis was detected up to 100% with the loss of continuous color signals in the entire circumference. After surgery, the positive predictive value was 100% for each of wiggling movement, dynamic intestinal movement, and continuous color signals in the entire circumference on color Doppler ultrasonography for detecting flap viability. Their negative predictive value was 100%, 7.1%, and 50%, respectively. CONCLUSIONS: During surgery, the continuous color signals in the entire circumference sign were useful with 100% negative predictive value for detecting the arterial thrombosis. After surgery, the wiggling movement sign very was useful with 100% positive and negative predictive values, enabling salvage surgery to be performed soon after detection of flap failure. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:3361-3369, 2023.

Development of a simultaneous and noninvasive measuring method using high-frame rate videography and motion analysis software for the assessment of facial palsy recovery in a rat model.

BACKGROUND: For the development of new therapeutic and reconstructive methods for facial nerve palsy, it is critical to validate them in animal models. This study developed a novel evaluation method using a high-speed camera and motion analysis software for rat facial paralysis models. The validity of the new method was verified using normal rats and rats with facial paralysis. METHODS: The whisker movement was recorded using a high-frame video camera. The video files were processed using motion analysis software, and the angular velocities were measured. The score was calculated as the percentage of movement on the side that had palsy compared with the movement on the normal side. Normal rats were used to examine which of the four indices of angular velocity is appropriate for this evaluation method. Using this method, two types of facial nerve palsy models were compared. Furthermore, the three agents that were predicted to promote axon regeneration from previous studies were evaluated. RESULTS: The two averages of the protraction and retraction movement velocities of the whiskers were considered as the most appropriate indicators for this new method. Compared with the saline group, all agent groups showed significant differences in the improvement of facial palsy recovery. CONCLUSIONS: This method is an evaluation method for the effects of therapeutic intervention for facial nerve paralysis in real time without sacrificing animals.

Lymphaticovenous anastomosis for treatment of refractory chylous ascites: A case report.

Chylous ascites, the leakage of lymphatic fluid into the abdominal cavity caused by lymphatic fluid stasis or lymphatic vessel damage, can be treated by lymphaticovenous anastomosis (LVA). We report rarely performed abdominal LVA to treat a case of refractory ascites possibly caused by ligation of the thoracic duct and pleurodesis in a man aged 60 years requiring weekly ascites drainage. Ligation was abandoned because the leakage site was not determined. The greater omentum (GO) was generally edematous and showed lymphatic effusion by gross appearance, and was considered suitable for LVA. We performed once LVA in the lymphatic vessels and veins of the GO using common microsurgical instrumentation and lateral anastomosis. Lymphatic vessels in the omentum were dilated to 2-3 mm, and LVA was simple. After LVA, GO edema improved. Postoperatively, the patient developed paralytic ileus, which improved within a few days, and the patient was discharged without any increase in ascites after starting to diet. One year post-surgery, there was no recurrence of ascites. LVA at the GO may be effective for the treatment of refractory chylous ascites because of its absorptive lymphatic draining capabilities and large transverse vessels.

Therapeutic Potential of the Prolyl Hydroxylase Inhibitor Roxadustat in a Mouse Hindlimb Lymphedema Model.

Background: Lymphedema is an intractable disease with no curative treatment available. Conservative treatment is the mainstay, and new drug treatment options are strongly needed. The purpose of this study was to investigate the effect of roxadustat, a prolyl-4-hydroxylase inhibitor, on lymphangiogenesis and its therapeutic effect on lymphedema in a radiation-free mouse hindlimb lymphedema model. Methods and Results: Male C57BL/6N mice (8-10 weeks old) were used for the lymphedema model. Mice were randomized to an experimental group receiving roxadustat or a control group. The circumferential ratio of the hindlimbs was evaluated, and lymphatic flow of the hindlimbs was compared by fluorescent lymphography up to 28 days postoperatively. The roxadustat group showed an early improvement in hindlimb circumference and stasis of lymphatic flow. The number and area of lymphatic vessels on postoperative day 7 were significantly larger and smaller, respectively, in the roxadustat group compared with the control group. Skin thickness and macrophage infiltration on postoperative day 7 were significantly reduced in the roxadustat group compared with the control group. The relative mRNA expression of hypoxia-inducible factor-1α (Hif-1α), vascular endothelial growth factor receptor-3 (VEGFR-3), vascular endothelial growth factor-C (VEGF-C), and Prospero homeobox 1 (Prox1) on postoperative day 4 was significantly higher in the roxadustat group compared with the control group. Conclusions: Roxadustat demonstrated a therapeutic effect in a murine model of hindlimb lymphedema through promotion of lymphangiogenesis through the activation of HIF-1α, VEGF-C, VEGFR-3, and Prox1, suggesting the potential of roxadustat as a therapeutic option in lymphedema.

Restoration of lymph flow by flap transfer can prevent severe lower extremity lymphedema after inguino-pelvic lymphadenectomy.

PURPOSE: Severe lymphedema is difficult to treat because of the associated extensive scar formation. Therefore, preventing scar formation might alleviate the severity of lymphedema following lymphadenectomy. In this study, we evaluated the usefulness of flap transfer, performed immediately after lymphadenectomy, for preventing scar formation. METHODS: Twenty-three patients with subcutaneous malignancy in a lower extremity, who underwent inguino-pelvic lymphadenectomy, were divided into groups based on whether flap transfer was performed. The severity of lymphedema was categorized according to the ratio of the circumference of the affected extremity to that of the unaffected extremity, as mild (< 20% increase in volume), moderate (20-40%), or severe (> 40%). RESULTS: In the 18 patients who underwent lymphadenectomy without flap transfer, lymphedema was classified as mild in 7, moderate in 7, and severe in 4. In the five patients who underwent lymphadenectomy with flap transfer, lymphedema was classified as mild in 4 and moderate in 1. This difference between the groups did not reach significance. CONCLUSIONS: The findings of this study suggest that flap transfer may help prevent scar formation and contribute to the restoration of lymph flow after lymphadenectomy.

Effectiveness and safety of percutaneous sclerotherapy using absolute ethanol and/or polidocanol for maxillofacial venous malformations involving the masticatory muscles: A case series.

OBJECTIVE: This study evaluated the effectiveness and safety of percutaneous sclerotherapy for maxillofacial venous malformations. STUDY DESIGN: Patients who had venous malformations involving the masticatory muscles and who underwent sclerotherapy were enrolled in this retrospective study. RESULTS: Twenty-four patients (13 female, 11 male; mean age 21 years) were analyzed. Major clinical symptoms were swelling (100%) and intralesional pain (54%). Intramuscular lesions involved the masseter muscle only in 38% of cases, both the masseter and temporalis muscles in 33%, all masticatory muscles in 21%, and the temporalis muscle only in 8%. Extramuscular involvement was observed in 58% of patients. Absolute ethanol and polidocanol were used as sclerosants. The mean number of sclerotherapy sessions per patient was 6.6 (range, 1-32). The mean follow-up duration after the first sclerotherapy session was 64.8 months (range, 6-178). The complications included paralysis of the facial nerve (25%), intraoral ulceration (8%), and hemoglobinuria (8%). The effectiveness of treatment was rated as excellent in 33% of cases, good in 46%, and fair in 21%. Better results were obtained in patients without extramuscular involvement. CONCLUSION: Percutaneous sclerotherapy can be effective and safe for maxillofacial intramuscular venous malformations, especially for localized lesions of the masseter muscle.

Refinements in the reconstruction of bisphosphonate-related osteonecrosis of the jaw.

The recommended treatment strategy for stage 3 bisphosphonate-related osteonecrosis of the jaw (BRONJ) is currently rigid plate fixation without bone reconstruction. However, a recent systematic review indicated the utility of microsurgical reconstruction after resection of BRONJ. Several types of flaps have been described but their applications are controversial. Here we present a detailed reconstruction plan for obtaining better outcomes in patients with maxillary and mandibular BRONJ. Given that progressive maxillary BRONJ is often invasive to the skin, including the eyelid, leading to functional loss such as leakage of discharge and ectropion, several revision surgeries are needed to increase the volume in the defect after the free flap transfer. For progressive mandibular BRONJ, hemi-mandibulectomy to subtotal mandibulectomy with an adequate margin from the necrotic bone is necessary, followed by a well-designed fibular free flap.

Sentinel node restoration by vascularized lymph node transfer in mice.

BACKGROUND: Recent reports have indicated that vascularized lymph node transfer (VLNT) may improve the impaired immunity in lymphedema but there has been no report concerning anti-cancer immunity. In the early tumor immune response, dendritic cells (DCs) participate in tumor recognition and antigen presentation in local lymphatics. Here, we investigated the impact of VLNT on DC dynamics against cancer in mouse models. METHODS: Forty-seven 8-week-old C57BL/6 N male mice were divided into three surgical groups: a VLNT model in which a vascularized inguinal lymph node (LN) flap was transferred into the ipsilateral fossa after a popliteal LN was removed; a LN dissection (LND) model in which the popliteal LN was dissected; and a control model in which a skin incision was made at the popliteal fossa and an ipsilateral inguinal LN was removed. Postoperative lymphatic flows were observed by indocyanine green lymphography and B16-F10-luc2 mouse melanoma were implanted into the ipsilateral footpad. The proportion of DCs in the transplanted nodes was measured by CD11c immunohistochemistry using digital imaging analysis 4 days after cancer implantation. Metastases to the lungs and LNs were quantitatively evaluated by luciferase assay 4 weeks after cancer implantation. RESULTS: After VLNT, lymphatic reconnection was observed in 59.2% of mice. The proportion of DCs was significantly higher in the VLNT group with lymphatic reconnection (8.6% ± 1.0%) than in the naïve LN (4.3% ± 0.4%) (p < .001). The tumor burden of lung metastases was significantly less in the VLNT group with lymphatic reconnection compared with the LND group (p = .049). CONCLUSIONS: Metastasis decreased in mice with reconnected lymphatics after VLNT. A possible explanation was that lymphatic restoration may have contributed to the tumor immune response by allowing DC migration to LNs.

Streptococcal Toxic Shock Syndrome in a Pediatric Patient With Intramuscular Venous Malformation in the Neck.

BACKGROUND: Streptococcal toxic shock syndrome (STSS) is diagnosed based on signs of shock with multiorgan system involvement, a generalized erythematous macular rash, and rapidly progressive and destructive soft tissue infection. CASE REPORT: The patient was a 2-year-old girl with intramuscular venous malformation in the neck in which an infection occurred, developing into STSS. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Group A streptococcal infections are common in children and usually have a mild clinical presentation, but may be life threatening in severe cases. Patients with venous malformations are known to have slow-flow anomalies with venous pooling, which can result in hypoxia and possible immune cell dysfunction. Thus, clinicians should be aware of STSS when a patient with venous malformation has a rapidly progressive infection.

Concordance in judgment of clinical borders of basal cell carcinomas in Japanese patients: A preliminary study of JCOG2005 (J-BASE-MARGIN).

Basal cell carcinoma is the most common type of skin cancer, and surgical excision with clear margins is the standard of care. Surgical margins are determined based on risk factors (high or low risk) for recurrence according to the National Comprehensive Cancer Network and Japanese basal cell carcinoma guidelines. The clarity of the clinical tumor border (well-defined or poorly defined) is considered a risk factor, and significant discrepancies in the judgment of clinical tumor borders among dermato-oncologists may occur. Therefore, we analyzed the dermato-oncologists' concordance in judging the clinical tumor border of basal cell carcinoma. Forty-seven dermato-oncologists (experts: 37; young trainees: 10) participated in this study. The datasets of clinical and dermoscopic photographs of 79 Japanese cases of head and neck basal cell carcinoma were used to determine the concordance in the judgment of clinical tumor border. The probability of the border that was selected more often was used to calculate the rater agreement rate for each dataset. Correct judgment was defined as a more frequently selected border, and the concordance rate of clarity of clinical tumor border for each dermato-oncologist was calculated based on the definition of the correct judgment. A median concordance rate of 85% or higher for all dermato-oncologists was predefined as an acceptable rate for clinical use. Of the 79 datasets, rater agreement rates were 80-100%, 60-79%, and 51-59% for 55, 19, and five datasets, respectively. The median concordance rate for all dermato-oncologists was 86% (interquartile range: 82-89%). There was no significant difference in the concordance rate between the experts and the trainees (median, 87% vs. 85.5%; p = 0.58). The concordance rates of dermato-oncologists for all datasets were relatively high and acceptable for clinical use.

Novel Surgical Technique for Correction of Incomplete Median Cleft Lip Deformity in Oral-Facial-Digital Syndrome Type II.

ABSTRACT: Oral-facial-digital syndromes (OFDSs) represent a heterogenous group of embryonic development disorders characterized by malformations of the face, oral cavity, and extremities. Oral-facial-digital syndrome type II is an autosomal recessive disease characterized by median cleft lip, gingival frenula, cleft lobulated tongue, and polydactyly. There are few reports on surgical techniques for correction of incomplete median cleft lip. Here we describe a novel surgical method that we used to correct an incomplete median cleft lip in a 5-year-old girl with oral-facial-digital syndrome type II. She had previously undergone surgery for congenital heart disease, oral anomalies, and polydactyly. Cheiloplasty was performed at 5 years and 8 months using a surgical approach that focused on repair of the median tubercle using lateral labial elements. A reasonably good Cupid's bow and median tubercle were achieved. Our technique for surgical correction of moderate incomplete median cleft lip provides adequate philtral height, vermillion fullness, and a good-shaped Cupid's bow.

Combined internal and external negative pressure wound therapy: breakthrough treatment for lymphocutaneous intractable fistula.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: CIEN is an effective and less invasive treatment modality than the conventional method of managing lymphocutaneous fistula.