Noninvasive visualization of the midline-crossing arterial variation in the deep inferior epigastric artery perforator flap using photoacoustic tomography for application in patients with abdominal scars.

BACKGROUND: The importance of the subcutaneous arterial network crossing the midline in transverse abdominal flaps has been reported. Photoacoustic tomography can be used to noninvasively visualize subcutaneous vascular networks. We applied this novel technology preoperatively in patients undergoing breast reconstruction to detect individual variations in the midline-crossing arteries. METHODS: Six patients scheduled to undergo breast reconstruction using free deep inferior epigastric artery perforator flaps were examined. Each scan of the 12 × 8-cm region took approximately 8 min. The accuracy of the tentative artery evaluation defined by photoacoustic tomography was compared with the arterial phase detected by intraoperative indocyanine green angiography. The number of perforator vessels used for the flap, surgical time for flap elevation, and perfusion area ratio were compared with those of the control group. RESULTS: The average match rate between tentative artery prediction by photoacoustic tomography and arterial-phase assessment by intraoperative angiography in five patients was 79.8%. Each midline-crossing artery showed individual variations. The photoacoustic tomography group (PAT-1 to 5) showed 1.8 perforators per flap, 163 min for flap elevation, and 93% perfusion area, with no significant differences from the control group (N = 5). A 63-year-old woman (PAT-6) with abdominal scars, including a midline abdominal incision, showed a preserved midline-crossing artery. The planned single perforator deep inferior epigastric perforator flap was successfully applied to the contralateral perfusion area. CONCLUSIONS: Photoacoustic tomography noninvasively visualizes the subcutaneous midline-crossing arterial networks. Understanding individual vascular variations can support preoperative planning and surgical indication of abdominal flaps, especially in patients with postsurgical scars.

Additional treatments after curettage of congenital melanocytic nevi in the craniofacial region: A report from a single center in Japan.

BACKGROUND: Congenital melanocytic nevus (CMN) is a benign skin lesion present from birth, which may present with a risk of malignant transformation if extensive. Curettage, a treatment method involving the removal of the superficial layer of the nevus, is often used in the early stages of life. However, recurrence of the nevus and postoperative scarring may present as problems. Additional treatments, such as resection and/or laser treatment, are regularly required after curettage, particularly in the craniofacial region. However, no systematic treatment strategy has been reported. This study investigated additional treatments used after curettage to treat CMN in the craniofacial region and compared the frequency of treatments with respect to specific sites. METHODS: CMN cases involving curettage as an initial treatment were retrospectively reviewed at Kyoto University Hospital between May 2019 and April 2022. RESULTS: This study comprised 23 cases. Curettage was performed at a mean of 3.8 (1-10) months of age. No additional treatments were provided for 80% of head CMN. Additional treatments were performed in all cases, including the forehead and cheek. Laser treatment was performed in 86% of eyelid CMN and 75% of nasal CMN. Tissue expansion and flap closure were used in 33% of forehead CMN and 33% of cheek CMN. CONCLUSIONS: Additional treatments used for CMN in the craniofacial region varied in accordance with the lesion site.

Double-Flap Elevation From the Ipsilateral Lower Extremity: The Anterior Approach to Fibula Osteo-Cutaneous Flap Elevation.

ABSTRACT: The free fibular flap has been elevated by a "lateral approach" from the posterior edge of the peroneal muscle for more than 40 years. However, in this approach, the surgical view is limited because flap elevation in mandibular reconstruction is performed simultaneously with tumor resection in the supine position, even when using positioning pillows. We herein propose an "anterior approach" as a new surgical method. We retrospectively investigated free fibular flap surgeries performed using the anterior approach, which consists of three anterior approaches, over a seven-year period. First, to avoid the course of the superficial peroneal nerve, the crural fascia was incised 1-2 cm posterior to the anterior edge of the peroneal muscle. The anterior edge of the peroneus muscle is detached from the anterior intermuscular septum. After performing osteotomies distal and proximal to the fibula, the interosseous membrane was incised from the anterior view. Pulling out the fibula to the anterior space between the anterior intermuscular septum and the peroneal muscle made the surgical field shallow. No postoperative superficial or deep peroneal nerve palsies were found in the 55 patients. Only one tourniquet was used in 31 of the 55 cases (56.4%), with an average of 95 min. Twenty-four patients (43.6%) required a second tourniquet 38 min after an interval. Only one tourniquet was used in 25 of the 30 (83.3%) cases in the last 3 years. Moreover, double flaps were used in 21 cases (38.2%), all of which involved ipsilateral ALT flaps. In 18 cases, double-flap elevation and prefabrication were successfully finished before the completion of tumor resection by otorhinolaryngologists.

Sustained increase of pinch strength after traction treatment for symptomatic distal interphalangeal joint osteoarthritis.

Background: Symptomatic distal interphalangeal joint osteoarthritis is a common joint disease that causes hand disability and reduces quality of life. There are few conservative treatment options for this condition. The purpose of this study was to investigate the effect of traction treatment on symptomatic distal interphalangeal joint osteoarthritis. Methods: This prospective, longitudinal study involved multiple time-series observations and within-subject controls. The most painful distal interphalangeal joints in patients with hand osteoarthritis were treated by daily, 15-min joint traction at home using a finger trap orthosis. The corresponding contralateral digits were used as within-subject controls. The primary outcome measure was two-point pinch strength, and the secondary outcome measures were radiographic findings and treatment adherence. Longitudinal and pairwise comparison analyses of the treated and control digits examined improvements in two-point pinch strength at months 1, 3, and 6 from baseline. The durability of treatment effects after treatment discontinuation was investigated at month 12. Results: Eighteen treated digits and 18 corresponding control digits were eligible for analysis. There was a significant increase in two-point pinch strength after 1-month traction, and this increase was maintained until month 6 despite the absence of radiographic changes. Compared to controls, significant improvement in two-point pinch strength relative to baseline was seen at every observation time point, with a moderate to large effect size. There was no time-treatment interaction. Treatment adherence was high. At months 3 and 6, around 60-80 % of digits were voluntarily treated. Pinch strength was comparable between months 6 and 12, with greater improvement than in the control group. Conclusion: Joint traction treatment can improve pinch strength in symptomatic distal interphalangeal joint osteoarthritis. Larger, randomized studies on traction treatment and the effect on hand function are warranted.

Sella turcica and facial bones: Morphological integration in the human fetal cranium.

OBJECTIVES: The cranial base plays a significant role in facial growth, and closer analyses of the morphological relationship between these two regions are needed to understand the morphogenesis of the face. Here, we aimed to study morphological integration between the sella turcica (ST) and facial bones during the fetal period using geometric morphometrics. MATERIALS AND METHODS: Magnetic resonance images of 47 human fetuses in the Kyoto Collection, with crown-rump lengths of 29.8-225 mm, were included in this study. Anatomical homologous landmarks and semilandmarks were registered on the facial bones and the midsagittal contour of the ST, respectively. The shape variations in the craniofacial skeleton and the ST were statistically investigated by reducing dimensionality using principal component analysis (PCA). Subsequently, the morphological integration between the facial bones and ST was investigated using two-block partial least squares (2B-PLS) analysis. RESULTS: PCA showed that small specimens represented the concave facial profile, including the mandibular protrusion and maxillary retrusion. The 2B-PLS showed a strong integration (RV coefficient = 0.523, r = .79, p < .01) between the facial bones and ST. The curvature of the anterior wall of the ST was highly associated with immature facial morphology characterized by a concave profile. CONCLUSION: The strong integration between the two regions suggested that the anterior ST may be associated with facial morphology. This result quantitatively confirms previous studies reporting ST deformities in facial anomalies and induces further research using postnatal subjects.

Apomorphine Suppresses the Progression of Steatohepatitis by Inhibiting Ferroptosis.

The role of ferroptosis in steatohepatitis development is largely unknown. We investigated (1) whether hepatocyte ferroptosis occurs in a gene-modified steatohepatitis model without modifying dietary components, (2) whether ferroptosis occurs at an early stage of steatohepatitis, and (3) whether apomorphine, recently reported as a ferroptosis inhibitor, can ameliorate steatohepatitis. Hepatocyte-specific PTEN KO mice were used. Huh 7 and primary cultured hepatocytes isolated from the mice were used in this study. The number of dead cells increased in 10-week-old PTEN KO mice. This cell death was suppressed by the administration of ferroptosis inhibitor ferrostatin-1 for 2 weeks. Apomorphine also ameliorated the severity of steatohepatitis. Treatment with ferroptosis inhibitors, including apomorphine, decreases the level of lipid peroxidase. Apomorphine suppressed cell death induced by RSL-3 (a ferroptosis inducer), which was not suppressed by apoptosis or necroptosis inhibitors. Apomorphine showed a radical trapping capacity with much more potent activity than ferrostatin-1 and Trolox, a soluble form of vitamin E. In addition, apomorphine activated nrf2 and its downstream genes, including HO-1 and xCT. In conclusion, ferroptosis occurs in steatohepatitis from an early stage in PTEN KO mice. In addition, apomorphine ameliorates the severity of steatohepatitis by inhibiting ferroptosis.

Simultaneous Reconstruction of the Bilateral Maxillae and Nasal Hard Structure Using a Vascularized and Nonvascularized Fibula.

Midfacial reconstruction for extensive defects of the hard nasal structures and bilateral maxillae is challenging. Postoperative radiotherapy causes skin contracture, making secondary reconstruction extremely difficult. A 57-year-old man underwent resection of the nasal bone, nasal cartilage, and hard palate for cancer of the nasal cavity. Postoperative radiotherapy (70 Gy) resulted in bilateral osteoradionecrosis. Severe depression deformity of the midface causes a disorder in closing the mouth, resulting in difficulty in conversation and oral intake. We performed simultaneous reconstruction of the bilateral maxillary and nasal hard structures using double free flaps (fibular osteocutaneous and anterolateral thigh flaps). A 16-cm right fibular osteocutaneous flap was elevated, and an 8-cm proximal bone was resected to obtain the length of the peroneal vessels. The distal 8 cm was cut into three pieces while maintaining the blood flow. The removed nonvascularized fibula was processed into two pieces of cortex: nasal bridge and columella. All areas of the skin island were de-epithelialized to bilaterally fill the maxillary sinuses. Next, the ipsilateral anterolateral thigh flap was elevated with the central 6-cm part for closure of the palate and the proximal area to fill the nasal cavity. The distal area consisted of a fascial flap to cover the reconstructed nasal structure. The chimeric double flap allowed for oral intake, conversation, and nasomaxillary prominence. Computed tomography performed 8 months postoperatively showed maintained bony structures. We used the extra fibula as a nonvascularized cortex piece to prevent infection and exposure, which enabled simultaneous reconstruction of the bilateral maxillae and hard nasal structure.

Multiple Buttress Reconstruction for Extended Total Maxillectomy by Mixed Use of Vascularized and Nonvascularized Fibula.

Reconstruction of extended total maxillectomy is challenging. This study aimed to isolate the skull base from the nasal cavity to avoid intracranial infection, cerebrospinal fluid fistula, and palate closure to maintain feeding and conversation. However, facial appearance and symmetry are important for quality of life. We report primary multiple buttress reconstruction using a removed nonvascularized fibula that reduced the risk of infection and exposure. A 74-year-old woman experienced a local recurrence of right maxillary sinus cancer after subtotal maxillectomy and postoperative radiotherapy (60 Gy). We performed extended total maxillectomy, including the right eyeball, orbit, temporal bone, palate, and zygomatic arch. Primary reconstruction was performed using fibular and anterolateral thigh free flaps. The proximal fibula bone was resected to obtain the length of the peroneal vessels, and the distal 9 cm of the fibula was made into two pieces while keeping the peroneal vessels attached. The nonvascularized 5-cm fibula was split sagittally with an L-shaped section to maintain the strength of the fragments. An anterolateral thigh flap was elevated from the ipsilateral thigh attached to the partial vastus lateralis muscle, which was divided into proximal (to the cheek skin and prosthetic eye bed) and distal (to the nasal cavity and palate) skin islands. Two nonvascularized bone fragments were fixed at the lateral and infraorbital rims. The dead space around the built-up pillar made of transferred bone was filled with vastus lateralis muscle to prevent infection and depression. This approach allowed for one-stage multiple buttress reconstruction for extended total maxillectomy.

Shaft structure of the first metatarsal contains a strong phylogenetic signal in apes and humans.

OBJECTIVES: Metatarsal bones constitute a key functional unit of the foot in primates. While the form-function relationships of metatarsals have been extensively studied, particularly in relation to the loss of the grasping ability of the foot in humans in contrast to apes, the effect of phyletic history on the metatarsal morphology and its variability remains largely unknown. MATERIALS AND METHODS: Here, we evaluate how the strength of the phylogenetic signal varies from the first to the fifth metatarsal in humans, chimpanzees, gorillas, orangutans, gibbons, and Japanese macaques. We use computed tomography imaging and morphometric mapping to quantify the second moment of area around and along the metatarsal shaft and evaluate the strength of the phylogenetic signal with multivariate K-statistics. RESULTS: The shaft structure of the first metatarsal, but not the others, correlates well with the phylogeny of apes and humans. DISCUSSION: Given the importance of the first metatarsal for grasping and bipedal/quadrupedal locomotion, the strong phylogenetic but weak functional signal in its structure is unexpected. These findings suggest that the evolutionary diversification of hominoid locomotor behaviors, including human bipedality, is only partly reflected in form-function relationships of key skeletal elements, and that phylogenetic history acted as a major evolutionary constraint.

Ramucirumab for advanced hepatocellular carcinoma in the current real world: a Japanese single-arm study post-REACH-2 (The R-evolution study).

This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child-Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child-Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study.

Potential of gelatin hydrogel nonwoven fabrics (Genocel) as a skin substitute in a diabetic mouse skin defect model.

Background: Gelatin hydrogel nonwoven fabrics (Genocel) are three-dimensional gelatin scaffolds that provide cells with space for proliferation, migration, and differentiation. They are expected to be an effective wound healing modality to treat intractable wounds, such as diabetic foot ulcers, because they enhance early neovascularization when used as a skin substitute. In this study, we explored the healing process of Genocel applied to skin defects in diabetic mice and compared it with that of a conventional skin substitute, Pelnac. Methods: Genocel and Pelnac sheets were used to treat skin defects on the backs of diabetic mice. On days 7 and 14, the remaining wound area was evaluated and specimens were harvested for HE, Azan, anti-CD31, CD68, and CD163 staining to assess neoepithelialization, granulation tissue formation, capillary formation, and macrophage infiltration. Results: Wounds treated with Genocel showed a wound healing process comparable to that of wounds treated with Pelnac. No significant differences were observed in the remaining wound area, neoepithelial length, granulation formation, number of pan-macrophages, or M2 ratio on days 7 and 14. The only significant difference was the number of induced M2 macrophages, which was higher in Pelnac group than in the Genocel group on day 7 (p < 0.05). Conclusions: Genocel showed similar healing effects in diabetic wounds as Pelnac and is considered an effective wound management modality for diabetic ulcers.

Efficacy of foam sclerotherapy with polidocanol for the management of oral venous malformations.

The present aimed to examine the effectiveness of polidocanol-based foam sclerotherapy for oral venous malformations (OVMs). The present study performed a retrospective analysis of patients with OVMs who underwent sclerotherapy using polidocanol. Patients achieving the complete resolution of OVM were categorized as having a complete response (CR), those with a reduction in size from the initial diagnosis were categorized as having a partial response (PR), those with no change in size as stable disease (SD), and those with an increase in size as progressive disease (PD). A total of 16 patients, comprising 4 males and 12 females, underwent treatment with polidocanol foam therapy, covering 22 affected areas. The treatment administered resulted in CR in 6 cases and PR in 10 cases, with no instances of SD or PD. Apart from localized injection site pain or swelling, there were no severe side-effects reported, such as circulatory dynamic changes or skin necrosis. On the whole, these findings underscore the effectiveness of foam sclerotherapy with polidocanol as a viable treatment for venous malformations in the oral and maxillofacial regions.

Repeated Fluid Accumulation around a Breast Implant Related to Synovial Metaplasia of the Capsule.

We must take special care when treating postoperative fluid accumulation around breast implants (BIs) to exclude any serious complications, including BI-associated anaplastic large cell lymphoma. However, most late-onset fluid accumulation is caused by other conditions, such as traumatic hematoma and residual postoperative seroma. Surgeons must choose whether to conservatively observe or remove such BIs, while also determining whether to perform partial capsulectomy or total capsulectomy to solve the problem of fluid accumulation. We treated a 72-year-old woman who noticed swelling in her right breast 4 years after undergoing bilateral BI reconstruction. Before she was referred to our hospital, the fluid had been drained by needle aspiration five times, but the swelling returned to a similar size within a month. No malignant findings were observed by needle-aspirated cytology or flow cytometry. The patient requested the simultaneous removal of the left BI. Therefore, we performed both BI removal with total capsulectomy on the right side and partial capsulectomy of the superficial layer on the left side. A pathological examination of the capsule on the right side indicated a chronic expanding hematoma and synovial metaplasia characterized by papillary projections rich in CD68-positive cells, thus indicating reactive synovial cells. In contrast, the left superficial capsule was much thinner and showed less synovial metaplasia. Our findings indicate the advantages of total capsulectomy to solve the problem of repeated serous fluid accumulation around BIs, according to histological changes in the capsule.

Multivariate Analysis of Risk Factors for Complications in Pediatric Tissue Expansion.

BACKGROUND: Tissue expanders represent one of the main surgical options for skin reconstruction in cases of tumors, traumalike burn injury, scar contracture, and alopecia. However, the tissue expander device is also associated with complications such as infection and extrusion. The aim of this study was to analyze risk factors for major complications of use of tissue expanders in pediatric patients using multivariate analysis. METHODS: A retrospective, single-center observational study was performed over 10 years in pediatric patients who were treated with tissue expanders for tumors, nevus, scars, burn reconstruction, and alopecia from April 2012 to March 2022. The primary outcome was overall complications per operation and expander, including infection and extrusion. Ten predictor variables were included as risk factors based on previous studies and as new factors considered important from clinical experience. Univariate and multivariate logistic regression analyses were performed to identify risk factors for major complications such as expander infection or extrusion. RESULTS: The study included 44 patients who underwent 92 operations using 238 tissue expanders. The overall complication rate per expander was 14.3%. Univariate logistic regression analysis identified associations of younger age, number of expanders used per operation, history of infection, and tissue expander locations with a higher complication rate. In multivariate logistic regression analysis, younger age (odds ratio, 1.14; P = 0.043) was associated with a high likelihood of expander complications. CONCLUSIONS: Younger age is an independent risk factor for tissue expander complications in pediatric patients. This factor should be considered in preoperative planning and discussions with the patient's family.

A Phase 2, Prospective, Multicenter, Single-Arm Trial of Transarterial Chemoembolization Therapy in Combination Strategy with Lenvatinib in Patients with Unresectable Intermediate-Stage Hepatocellular Carcinoma: TACTICS-L Trial.

Introduction: Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC), but recurrence after TACE is common. The present phase 2, prospective, multicenter, single-arm trial, the TACTICS-L trial, investigated the efficacy and safety of TACE plus lenvatinib (LEN), a drug that more strongly promotes vascular normalization and has a better objective response rate (ORR) than sorafenib (jRCTs031180074). Methods: Participants were patients with HCC who had not previously received systemic therapy, hepatic arterial infusion chemotherapy, or immunotherapy and who were ineligible for resection or percutaneous ablation therapy. LEN was to be administered 14-21 days before the first TACE, stopped 2 days before TACE, and resumed 3 days after TACE. Key inclusion criteria were unresectable HCC, Child-Pugh A liver function, 0-2 prior TACE sessions, tumor size ≤10 cm, number of tumors ≤10, and ECOG performance status 0-1. Key exclusion criteria were vascular invasion and extrahepatic spread. The primary endpoint was progression-free survival (PFS) by RECICL, and secondary endpoints were time to untreatable progression, ORR, overall survival (OS), and safety. Results: A total of 62 HCC patients were enrolled in this trial. The median age was 72 years, 77.4% of patients were men, and 95.2% had PS 0. The primary endpoint of median PFS was 28.0 months (90% confidence interval [CI] 25.1-31.0) after a minimum 24 months of follow-up. The secondary endpoint of median OS was not reached (90% CI 35.5 months-NR). LEN-TACE achieved a high response rate and high complete response (CR) rate (4 weeks after the first TACE: ORR 79.0%, CR rate 53.2%; best response: ORR 88.7%, CR rate 67.7%) by RECICL. Exploratory subgroup analyses showed that the characteristics of responders/nonresponders (ORR and CR rate) were similar and that LEN-TACE would be effective in all subgroups, including the population in whom TACE alone would be less likely to be curative (e.g., patients with the non-simple nodular type or a high tumor burden). The relative dose intensity of LEN before the first TACE was important for achieving higher CR rate/ORR by LEN-TACE. No new safety concerns were observed. Conclusion: The results of this trial provide encouraging evidence, supporting the efficacy and favorable safety profile of LEN-TACE in patients who are ineligible for locoregional therapy.

Evaluation of adipogenesis over time using a novel bioabsorbable implant without the addition of exogenous cells or growth factors.

Background: Breast reconstruction is crucial for patients who have undergone mastectomy for breast cancer. Our bioabsorbable implants comprising an outer poly-l-lactic acid mesh and an inner component filled with collagen sponge promote and retain adipogenesis in vivo without the addition of exogenous cells or growth factors. In this study, we evaluated adipogenesis over time histologically and at the gene expression level using this implant in a rodent model. Methods: The implants were inserted in the inguinal and dorsal regions of the animals. At 1, 3, 6, and 12 months post-operation, the weight, volume, and histological assessment of all newly formed tissue were performed. We analyzed the formation of new adipose tissue using multiphoton microscopy and RNA sequencing. Results: Both in the inguinal and dorsal regions, adipose tissue began to form 1 month post-operation in the peripheral area. Angiogenesis into implants was observed until 3 months. At 6 months, microvessels matured and the amount of newly generated adipose tissue peaked and was uniformly distributed inside implants. The amount of newly generated adipose tissue decreased from 6 to 12 months but at 12 months, adipose tissue was equivalent to the native tissue histologically and in terms of gene expression. Conclusions: Our bioabsorbable implants could induce normal adipogenesis into the implants after subcutaneous implantation. Our implants can serve as a novel and safe material for breast reconstruction without requiring exogenous cells or growth factors.

PreFlap: From Photoacoustic Tomography Images to Vascular Mapping Sheets for Improved Preoperative Flap Evaluation.

OBJECTIVE: Advancements in technology have improved image acquisition and processing in the field of medical imaging, giving medical doctors the tools to implement effective medical care. In plastic surgery, despite advances in anatomical knowledge and technology, problems in preoperative planning for flap surgery remain. METHODS: In this study, we propose a new protocol to analyze three-dimensional (3D) Photoacoustic tomography images and generate two-dimensional (2D) mapping sheets that can help surgeons identify perforators and the perfusion territory during preoperative planning. The core of this protocol is PreFlap, a new algorithm that converts 3D photoacoustic tomography images into 2D vascular mapping images. CONCLUSION: Experimental results demonstrate that PreFlap can improve preoperative flap evaluation, thus can greatly saving surgeons' time and improving surgical outcomes.

A Prospective Study Exploring the Safety and Efficacy of Lenvatinib for Patients with Advanced Hepatocellular Carcinoma and High Tumor Burden: The LAUNCH Study.

PURPOSE: This study aimed to investigate the safety and efficacy of lenvatinib in real-world settings, including patients excluded from the REFLECT trial, a phase III trial that compared lenvatinib with sorafenib. PATIENTS AND METHODS: This multicenter, nonrandomized, open-label prospective study was conducted at 10 medical facilities in Japan (jRCTs031190017). Eligible patients had advanced hepatocellular carcinoma (HCC) and were suitable for lenvatinib therapy. The study included patients with high tumor burden (with >50% intrahepatic tumor volume, main portal vein invasion, or bile duct invasion), Child-Pugh B status, and receiving lenvatinib as second-line therapy following atezolizumab plus bevacizumab. RESULTS: From December 2019 to September 2021, 59 patients were analyzed (47 and 12 patients with Child-Pugh A and B, respectively). In patients with Child-Pugh A, the frequency of aspartate aminotransferase elevation was high (72.7%) in the high-burden group. No other significant ad verse events (AE) were observed even in second-line treatment. However, patients with Child-Pugh B had high incidence of grade ≥3 AE (100.0%) and high discontinuation rates caused by AE (33.3%) compared with patients with Child-Pugh A (80.9% and 17.0%, respectively). Median progression-free survival was 6.4 and 2.5 months and median overall survival was 19.7 and 4.1 months in Child-Pugh A and B, respectively. Lenvatinib plasma concentration was higher in patients with Child-Pugh B on days 8 and 15 and correlated with dose modifications and lower relative dose intensity. CONCLUSIONS: Lenvatinib is safe and effective for advanced HCC in patients with Child-Pugh A, even with high tumor burden. However, it carries a higher risk of AE and may not provide adequate efficacy for patients with Child-Pugh B status.

Flap Viability Evaluation Using a Tissue Oximetry Camera as an Alternative to Indocyanine Green Fluorescence Imaging.

Indocyanine green (ICG) fluorescence imaging is useful for assessing flap viability; however, it is associated with a risk of anaphylactic shock, even in patients with no history of drug allergies. SnapshotNIR is a noncontact, camera-type handheld tissue oximeter that can measure the tissue oxygen saturation of the body surface. The device emits red and near infrared light wavelengths and then optimizes the measurement of the differential reflectance from oxygenated and deoxygenated hemoglobin, and StO2 is calculated. A 20 × 15 cm surgical field can be evaluated in less than 3 seconds by holding the camera at a distance of 30 cm. We applied this device at zone II in a deep inferior epigastric perforator (DIEP) flap, and compared the findings with the border of flap perfusion detected by ICG imaging. Left breast reconstruction using a free DIEP flap was performed for a 60-year-old woman. The DIEP flap was vascularized by a perforator vessel coursing to the right abdominis muscle. First, Diagnogreen (5 mg; Daiichi Sankyo Co., Tokyo, Japan) was intravenously injected, and the ICG fluorescence perfusion border detected by PDE-neo (Hamamatsu Photonics, Hamamatsu City, Shizuoka, Japan) was determined. The ICG border was defined by two reconstructive surgeons after fluorescence had spread out for 2 minutes. Next, zones Ⅱ and Ⅳ of the DIEP flap, contralateral to the perforator, were evaluated using photographs obtained by SnapshotNIR. There were significant StO2 value differences between the ICG-negative area and ICG-positive area. This device can be widely applied in the noninvasive evaluation of flap viability.