Analysis of cancer-associated fibroblasts and the epithelial-mesenchymal transition in cutaneous basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.

Activated cancer-associated fibroblasts (CAFs) and fibroblasts that have undergone the epithelial-mesenchymal transition (EMT) in cancer stroma contribute to tumor progression and metastasis. However, no reports have investigated the CAF phenotype and its clinicopathological relevance in cutaneous malignant tumors, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM). Here, we investigated the CAF phenotype in cutaneous malignant tumors based on their histology and immunohistochemical expression of CAF-related markers, including adipocyte enhancer-binding protein 1 (AEBP1), podoplanin, platelet-derived growth factor receptor α (PDGFRα), PDGFRß, fibroblast activating protein (FAP), CD10, S100A4, α-smooth muscle actin (α-SMA), and EMT-related markers (Zeb1, Slug, and Twist). In addition, we assessed the role of the CAF phenotype in cutaneous malignant cancers using hierarchical cluster analysis. Consequently, 3 subgroups were stratified based on the expression pattern of CAF- and EMT-related markers. Subgroup 1 was characterized by low expression of AEBP1, PDGFRα, PDGFRß, FAP and Slug, whereas subgroup 2 was closely associated with high expression of PDGFRß, S100A4 and Twist. In addition, high expression levels of podoplanin, PDGFRß, CD10, S100A4, α-SMA, Zeb1, Slug and Twist were observed in subgroup 3. High expression of CD10 was commonly found in all 3 subgroups. These subgroups were correlated with histologic subtypes, that is, subgroup 1, MM; subgroup 2, BCC; and subgroup 3, SCC. We suggest that the expression pattern of CAF- and EMT-related proteins plays crucial roles in the progression of BCC, SCC, and MM.

The Classification of Swanson for Congenital Anomalies of Upper Limb Modified by the Japanese Society for Surgery of the Hand (JSSH).

The aim of this study is to introduce the classification of Swanson for congenital anomalies of upper limb modified by the Japanese Society for Surgery of the Hand (the JSSH modification) in English. The Swanson classification has been widely accepted by most hand surgeons. However, several authors have suggested that complex cases, particularly those involving the complex spectrum of cleft hand and symbrachydactyly, are difficult to classify into the classification schemes. In the JSSH modification, brachysyndactyly, so-called atypical cleft hand and transverse deficiency are included under the same concept of transverse deficiency. Cleft hand, central polydactyly, and syndactyly are included in the same category of abnormal induction of digital rays. We believe that the JSSH modification system is effective in providing hand surgeons with the clinical features and conditions for congenital anomalies.

Reconstruction of the sacral region using the lumbo-gluteal sensory flap.

PURPOSE: Local skin flaps are used for reconstruction of sacral decubitus ulcers because of their structural endurance against the patient's weight. However, a major concern is associated with decubitus recurrence after repair. Sensory flaps are one choice to prevent recurrence. Thus, we reconstructed sacral decubitus ulcers using Nakajima's lumbo-gluteal flap as a sensory flap. PATIENTS AND METHODS: Two patients with unstable sacral scars caused by decubitus ulcers were treated operatively. Neither had spinal cord injury, and buttock sensation thus remained. The flap's proximal end was designed on the posterior iliac crest and included the lateral dorsal cutaneous branch of the fourth lumbar artery as examined preoperatively with a Doppler stethoscope. The distal end was beyond the gluteal fold in case 1, but not in case 2. We subcutaneously dissected the vascular pedicle and the superior cluneal nerve located at the proximal portion of the flap after resection of the unstable scar. We then elevated the flap beneath the fascia of the gluteus maximus of the right buttock, preserving the nerve, artery and subcutaneous tissue as one pedicle, and transferred the flap to the defect. RESULTS: In case 1, 2 cm of the distal end of the flap was lost. The sensation of the proximal two-thirds of the flap was identical to that of the contralateral buttock. However, the distal one-third of the flap, which was elevated from the area caudal to the gluteal fold, had insufficient sensation. Case 2 had complete flap survival and sufficient sensation in all areas of the flap. Decubitus recurrence has not occurred in 7 years in case 1 and in 9 months in case 2. CONCLUSION: This flap is useful for reconstruction of sacral decubitus ulcers if sensory function of the buttock remains and may be best designed as not extending beyond the gluteal fold.

Alveolar reconstruction by distraction osteogenesis under unfavorable conditions.

We present a patient who underwent alveolar reconstruction using vertical mandibular lengthening by distraction osteogenesis under unfavorable conditions. Part of the alveolar bone in the center of the mandible was resected, together with a squamous cell carcinoma located on the oral floor. We used vertical mandibular lengthening from the region of the remaining mandible inferior to the bony defect to reconstruct the alveolus, combined with a free musculocutaneous flap as a cover. However, the transferred flap underwent complete necrosis and was replaced with another flap on the seventh postoperative day. Radiotherapy at a total dose of 50 Gy was administered from day 75 to day 109 after completion of the distraction, because of suspected residual tumor. Despite the severe conditions, most of the distraction gap became filled with new bone. This case indicates that distraction osteogenesis can be used even in irradiated or poorly vascularized areas, as in our patient.

Facial nerve reconstruction using a vascularized lateral femoral cutaneous nerve graft based on the superficial circumflex iliac artery system: an application of the inferolateral extension of the groin flap.

The use of an inferolateral extension technique of a groin flap has previously been reported. This technique involves harvesting an extended portion from the anterolateral thigh, including the lateral femoral cutaneous nerve (LFCN) and its accompanying vessels, attached to a groin flap via communications between the LFCN-accompanying vessels and the superficial circumflex iliac artery (SCIA) system. In this study, we used this technique involving a vascularized LFCN combined with a groin flap to reconstruct a facial nerve defect. The patient was a 58-year-old man with a salivary duct carcinoma in the left parotid gland. Tumor ablation resulted in a defect of the skin and soft tissue including all branches of the facial nerve. A free groin flap was harvested based on the SCIA system, composed of the LFCN and a small monitoring flap, which were nourished by the LFCN-accompanying vessels and by communication with the SCIA system. The LFCN was transplanted into the gaps in the facial nerve branches as a cable graft, and the skin flap was used to cover and fill the soft tissue defect. The postoperative course was uneventful and satisfactory facial animation was obtained. This represents a possible technique for nerve reconstruction using a vascularized nerve graft.

Reconstruction of the cervical trachea using a prefabricated corticoperiosteal flap from the femur.

We treated a severe cervical fistula with a defect of tracheal cartilage using prefabrication of a corticoperiosteal flap combined with a cutaneous flap.The patient was a 16-year-old male with a cervical tracheal fistula that developed after a tracheostomy. Almost all the circumference of the trachea just below the cricoid cartilage up to the 4th tracheal cartilage had been lost.The reconstruction was performed in 2 series of operations as follows; repair of tracheal framework using a prefabricated corticoperiosteal flap, which was harvested from the femur and composed of a saphenous flap, and then complete closure using a local hinge flap and a free auricular cartilage graft. A free corticoperiosteal flap composed of a saphenous flap was transferred to the site just lateral to the defect. The corticoperiosteal flap, which has a flat shape, was bent in a reverse U-shaped semitubular fashion and the mucosal grafts were used to cover its inner surface. Two months later, the prefabricated corticoperiosteal flap and the saphenous flap were transposed leaving a part of the fistula as a tracheostoma. The remaining tracheostoma was closed secondarily. A satisfactory and stable result was obtained over an 8-year follow-up period.We believe that the procedure demonstrated here should be considered as a choice for the stable reconstruction of a cervical trachea.

Inferolateral extension of the groin flap based on the artery accompanying the lateral femoral cutaneous nerve.

The authors reconstructed hand defects using a new type of the extended groin flap in two patients. The extended portion includes the lateral femoral cutaneous nerve (LFCN) and the artery accompanying the LFCN (LFCA). Circulation to the extended portion was maintained by the communicating branches between the LFCA and the superficial circumflex iliac artery (SCIA). The flap was used as a pedicle flap in one patient and as a free flap in the other patient. The extended portion was elevated as an island flap based on LFCA in the latter. These flaps, including the extended portion, were transferred successfully. We have already reported use of the inferior extension of the groin flap based on the descending branch of the SCIA, in 2002. However, the extension technique described here is a different type of extension, due to the use of a different nutrient vessel. We believe that this new technique increases the usefulness of the groin flap.

Orbicularis oris myomucosal island flap transfer to the nose.

We developed the orbicularis oris myomucosal island flap (OOMMIF) to reconstruct the nasal lining in one stage. The OOMMIF blood supply derives from the intramuscular vascular network which communicates with the submucosal vascular plexus via the vascular network formed by the deep ascending branches of the superior labial artery. An oral mucosal flap of approximately 2 x 3cm can be harvested from the upper lip pedicled solely on the orbicularis oris muscle. We transferred this flap to a nasal lining defect located in the ala in four patients, the nasal floor in two patients, and the columella in two patients. The flap donor site was closed primarily. All flaps took completely with satisfactory results. Minor complications included slight asymmetry of the vermilion height due to donor site contracture in one patient and flap drooping in two patients corrected by secondary debulking. Upper lip functional loss was not observed, although upper lip hypoaesthesia occurred in one patient, which disappeared within 6 months. An OOMMIF can be easily elevated with minimal donor site morbidity. Thus, the OOMMIF is a good candidate for one-stage reconstruction of small nasal lining defects.

Efficacy of distraction osteogenesis for mandibular reconstruction in previously irradiated areas: clinical experiences.

The efficacy of distraction osteogenesis in an irradiated area is controversial, although this procedure is now widely used in the field of craniomaxillofacial surgery. We report the clinical results from 4 patients with mandibular defects treated by lengthening of the irradiated mandibles. All patients had a mandibular defect caused by ablation of a malignant tumor. They had undergone radiotherapy at a total dose of 30 to 50 Gy to the surgical site after tumorectomy. Distraction osteogenesis was used as the secondary reconstruction method in 6 sites of the remaining irradiated mandibles and in 1 site of the transferred vascularized scapula after radiotherapy. The transported segment was obtained by corticotomy with an initial gap of 0 to 2 mm, and internal extension plates were used. Distraction was commenced after a latency period of 7 to 10 days and performed at the rate of 0.25 to 1.0 mm/d. The total amount of distraction and consolidation periods ranged from 15 to 25 mm and 120 to 193 days, respectively. In 5 of the 6 sites in the remaining irradiated mandibles, satisfactory bone formation in the distraction gap was observed, although a fracture after new bone formation was observed in 1 site. Fibrous callus formation was observed in 1 irradiated site only, and satisfactory results were obtained in another site of transferred vascularized scapula in the same patient. From these experiences, we believe that distraction may provide a reconstruction option for mandibular defects even under irradiated conditions because the procedure is simple and less invasive.

Operative technique to harvest an arterial flap from the posterolateral calf region: how can we elevate a lateral gastrocnemius perforating artery flap safely?

The posterior calf region is a useful donor site for skin or composite flaps including muscle and/or nerves. We reported the first clinical use of the lateral gastrocnemius perforating artery flap including a vascularized sural nerve in 2003. This flap was elevated based on a perforator arising from the lateral head of the gastrocnemius muscle. However, we have since encountered vascular variations in these perforators. We subsequently developed a reliable technique for harvesting this flap in the course of treating 10 patients. Safe flap elevation from the lateral aspect of the posterior calf requires preservation of one of the superficial sural arteries until reliable perforators arising from gastrocnemius muscle lateral head are encountered during dissection. When such perforators are not observed, nutrient vessels such as superficial sural arteries or muscle perforators originating from vessels other than the lateral sural artery must be selected as a flap pedicle.

Secondary craniofacial reconstruction of huge frontoethmoidal encephalomeningocele after primary neurosurgical repair.

Frontoethmoidal encephalomeningocele is a congenital herniation of intracranial contents, including meninges, brain and part of the ventricle, through a bony defect in the skull at the junction of the frontal and ethmoid bones. Management involves meticulous preoperative assessment using computed tomography scans and magnetic resonance imaging, and surgical repair of the central nervous system, skeletal deformities of the orbit, downward displacement of the medial canthi, upward displacement of the eyebrows, and nasal deformities. Frontoethmoidal encephaloceles are best operated on via a craniofacial approach which enables repair of the central nervous system and skeletal deformities in one stage. However, a two-stage reconstruction must be considered when a prolonged operative time is expected or the patient's general condition increases the risks. There have only been a few reports of two-stage reconstructions. We performed a two-stage reconstruction of a huge frontoethmoidal encephalomeningocele, with neurosurgical repair during the first procedure and craniofacial reconstruction during the second procedure. We report on the surgical procedures and the problems encountered.

Reconstruction of a severe maxillofacial deformity after tumorectomy and irradiation using distraction osteogenesis and LeFort I osteotomy before vascularized bone graft.

We present the successful reconstruction of a large mandibular defect with a severe maxillofacial deformity after malignant tumor resection and irradiation. The patient was a 16-year-old boy with a defect in the left mandible, which extended from the mandibular body to the condylar process and hypoplasia of the maxillozygomatic complex on the left side as a result of ablation and radiotherapy of a grown rhabdomyosarcoma in the left infratemporal fossa at the age of 10. We planned a two-stage reconstruction because of his wide mandibular defect and hypoplasia. LeFort I type osteotomy to correct the maxillary declination was combined with mandibular lengthening to decrease the width of the defect in the first stage. New bone formation was confirmed at the distraction site 4 months after surgery, and the second stage was performed. A free latissimus dorsi myocutaneous flap with a vascularized scapula and rib was transferred to reconstruct the ramus of the mandible, zygomatic arch, and soft tissues. This procedure resulted in satisfactory results. In conclusion, the combination of distraction osteogenesis and microsurgical bone transplantation facilitated the straightforward reconstruction of a three-dimensional deformity with huge bony defects. We think that this combined surgical procedure will become a favorable option in the treatment of severe maxillomandibular deformities with bone defects.

Gastrocnemius perforating artery flap including vascularized sural nerve.

A degree of communication was found between the superficial sural artery (the concomitant vessel of the sural nerve) and the muscle perforators from the gastrocnemius muscle, together with the cutaneous branches of the peroneal artery. A fasciocutaneous flap designed in the posterior calf region, including the vascularized sural nerve, was elevated based on the perforating artery of the gastrocnemius. This compound flap was used to reconstruct facial nerves and soft-tissue defects created by resection of malignant tumors in three patients. The results were satisfactory, and facial animation returned in two patients, who were followed-up for more than 6 months. This compound flap offers several advantages, such as a long vascular pedicle with a sufficient diameter and a rich blood supply for the sural nerve and fasciocutaneous flap. This new technique should become another choice for vascularized sural nerve grafts, when the superficial sural artery or the cutaneous branches of the peroneal artery are not adequate for flap elevation or microsurgical anastomoses.

Inferior extension of the groin flap based on the descending branch of the superficial circumflex iliac artery.

The authors present a groin flap which was extended inferiorly and included the descending branch of the superficial circumflex iliac artery (SCIA) as a new alternative technique. Little research has been previously done on the descending branch of the SCIA, but the authors found clinically that this small branch was consistently present, and decided to make use of it to extend the groin flap inferiorly. The procedure extending the groin flap was successfully applied in three patients, one with a degloving injury of the leg, and two with progressive hemifacial atrophy. The extended portion was elevated as an island flap based on the descending branch in the patient with the degloving injury. Results revealed that this technique added a new axial portion located on the upper median thigh to the vascular territory of the conventional groin flap, and could be used to make a two-island groin flap.