Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis.

FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1-5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1 activates a CAMK2-CD44-SRC axis that promotes YAP1 nuclear translocation and ZEB1 expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2 expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state.

Custom designed radial forearm free flap for reconstruction of nasomaxillary defects: Report of two cases.

Nasal amputation and nasomaxillary defects, need to reconstruct the internal lining, osteochondral structure, and external coating of the nose. Authors report a 70-year-old male and a 65-year-old female treated for nasomaxillary defects (Brown JS, Shaw RJ. The Lancet Oncology 2010;11:1001-1008) due to squamous cell carcinoma (SCC) where the tip of the nose was preserved. A new custom design of the radial forearm free flap (RFFF) consisting on a subcutaneous tissue (SCT) component, a skin paddle for the internal nasal vault lining, and a skin paddle for the external nasal skin coating was raised to treat both total thickness nasal defects. The dimension of each skin paddle corresponds to the defect measurements. The skin incisions of the custom design correspond to those of a conventional RFFF. The SCT component was harvested in a subcutaneous plane continuously with the skin island for the internal nasal lining which is drawn on the ulnar skin of the forearm. The component for the external nasal coating was drawn on the radial skin area of the flap. No postoperative complications and a satisfactory outcome was reported after 1 year of follow-up. This new custom design of the RFFF is described for reconstruction of nasomaxillary defects when the tip of the nose is preserved.

Midface Advancement in a Simple Approach.

BACKGROUND: Midface advancement is a keystone intervention in the treatment plan of syndromic hypoplasia of the midface. Although earlier authors had been using a combination of smaller incisions to acquire enough access to perform the different osteotomies, Tessier popularized the bicoronal incision. This approach can be time-consuming however and leaves an ear-to-ear scar. The authors describe an endoscopically assisted piezo-electric Le Fort III osteotomy performed through minimal invasive access. The cutaneous incision was limited to a single-short mid-glabellar vertical scar (8 mm) to perform the nasofrontal and septum osteotomy. Further osteotomies are performed through a 1.5 cm intraoral incision and a transconjunctival approach with a retrocaruncular extension. A lateral canthotomy was avoided to lower the risk of postoperative eyelid malposition. METHODS: A feasibility study using 2 fresh nonfrozen cadaver heads. CONCLUSION: The minimally invasive Le Fort III approach is feasible and efficacious for clinical use in a cadaveric setup.

Tissue-engineered oral mucosa grafts for intraoral lining reconstruction of the maxilla and mandible with a fibula flap.

PURPOSE: Many types of soft tissue grafts have been used for grafting or prelaminating bone flaps for intraoral lining reconstruction. The best results are achieved when prelaminating free flaps with mucosal grafts. We suggest a new approach to obtain keratinized mucosa over a fibula flap using full-thickness, engineered, autologous oral mucosa. PATIENTS AND METHODS: We report on a pilot study for grafting fibula flaps for mandibular and maxilla reconstruction with full-thickness tissue-engineered autologous oral mucosa. We describe 2 different techniques: prelaminating the fibula flap and second-stage grafting of the fibula after mandibular reconstruction. Preparation of the full-thickness tissue-engineered oral mucosa is also described. RESULTS: The clinical outcome of the tissue-engineered intraoral lining reconstruction and response after implant placement are reported. A peri-implant granulation tissue response was not observed when prelaminating the fibula, and little response was observed when intraoral grafting was performed. CONCLUSION: Tissue engineering represents an alternative method by which to obtain sufficient autologous tissue for reconstructing mucosal oral defects. The full-thickness engineered autologous oral mucosa offers definite advantages in terms of reconstruction planning, donor site morbidity, and quality of the intraoral soft tissue reconstruction, thereby restoring native tissue and avoiding peri-implant tissue complications.

Customized Subperiosteal Implants for the Rehabilitation of Atrophic Jaws: A Consensus Report and Literature Review.

(1) Background: The aim was to perform a literature review on customized subperiosteal implants (CSIs) and provide clinical guidelines based on the results of an expert consensus meeting held in 2023. (2) Methods: A literature search was performed in Pubmed (MEDLINE) in July 2023, including case series and cohort studies with a minimum follow-up of 6 months that analyzed totally or partially edentulous patients treated with CSIs. Previously, an expert consensus meeting had been held in May 2023 to establish the most relevant clinical guidelines. (3) Results: Six papers (four case series and two retrospective cohort studies) were finally included in the review. Biological and mechanical complication rates ranged from 5.7% to 43.8% and from 6.3% to 20%, respectively. Thorough digital planning to ensure the passive fit of the CSI is mandatory to avoid implant failure. (4) Conclusions: CSIs are a promising treatment option for rehabilitating edentulous patients with atrophic jaws; they seem to have an excellent short-term survival rate, a low incidence of major complications, and less morbidity in comparison with complex bone grafting procedures. As the available data on the use of CSIs are very scarce, it is not possible to establish clinical recommendations based on scientific evidence.

Rhytidectomy approach for mandibular reconstruction with microvascular free flaps after resection of mandibular benign tumors.

PURPOSE: Microvascular surgery has become the preferred method for mandibular reconstruction. A neck incision frequently is required for malignant tumor resections to carry out the dissection. The authors suggest a rhytidectomy approach for mandibular reconstruction with microvascular free flaps after the resection of benign tumors. PATIENTS AND METHODS: Seven patients with lateral mandibular defects resulting from resection of benign mandibular tumors were treated in the author's department. A combined rhytidectomy approach with an intraoral incision was used for mandibular resection and reconstruction of the defects using vascularized free osseous flaps. RESULTS: The study was comprised of 3 men and 4 women with a mean age of 37.57 years (range, 28 to 50 years). Follow-up ranged from 9 to 87 months after surgery (mean, 56.28 months). The iliac crest was used for reconstruction in 6 patients, whereas the fibula was used in 1 patient. Transient paresis of the marginal nerve was observed in 2 patients. Flap loss occurred in 1 patient and required repeat microvascular reconstructive surgery. Dental rehabilitation with osseointegrated implants was performed in 4 patients. At the end of the follow-up period, successful mandibular reconstruction was achieved in all patients. Functional outcome was regarded as excellent in all patients, whereas esthetic outcome was judged excellent in 6 patients and good in 1 patient. CONCLUSIONS: A rhytidectomy approach combined with an intraoral incision for microvascular mandibular reconstruction after the resection of benign tumors is a feasible technique that provides good exposure of the anatomic structures, an inconspicuous facial scar, and adequate facial contour and symmetry. Excellent clinical results are reported with the use of this technique, which should be included in the surgical armamentarium for mandibular reconstruction.

Functional outcomes after glossectomies: Pilot study on use of a thrombin-fibrinogen biosponge (TachoSil).

OBJECTIVE: The aim of this study was to investigate whether the use of a thrombin-fibrinogen biosponge (TachoSil) has any advantage in tongue healing. STUDY DESIGN: A retrospective study with 30 patients treated with partial glossectomy (below half a tongue) was designed. We compared the results from a group using the biosponge (n =15 patients) and a control group (n = 15). Variables taken into consideration were bolus clearance, frenulum flexibility, and oral transit time. With these parameters, we formulated a "tongue remaining functional" (TRF) scale to assess tongue functionality after the surgery. We also evaluated long-term quality of life by using the Functional Intraoral Glasgow Scale (FIGS). RESULTS: In this study, TRF score, bolus clearance, oral transit time, and frenulum flexibility were significantly improved in the biosponge group. However, there were no differences between the 2 groups in the FIGS scores. CONCLUSIONS: The use of the biosponge in this pilot study showed positive long-term effects in lingual healing and functionality after partial glossectomies.

Lemierre Syndrome associated with dental infections. Report of one case and review of the literature.

The first publication on Lemierre Syndrome appears in 1936 by Lemierre. It is defined as an "oropharynx bacterial infection characterized by the thrombophlebitis in the internal jugular vein, derived in a systemic septic embolism". In 81% of the cases, the Fusobacterium necrophorum is the most frequent etiologic agent. Fever is the most common symptom, but it can depending on the primary infection, tonsillitis, mastoiditis or odontogenic infection. According to the literature the mortality is very low, but with a significant morbidity, that is why the diagnosis and early treatment is very important. The diagnosis it's clinical, even though the CT scan and other diagnosis methods (echography, MRI) help to determine the extent of the infection. It's necessary to administer the antibiotics endovenous at high dose, (keeping in mind that the most frequent micro organism is anaerobic), and vital support measures if necessary. We present a case report of Lemierre Syndrome associated to an odonthogenic infection caused by the 4.8 molar.

SPECT-CT and intraoperative portable gamma-camera detection protocol for sentinel lymph node biopsy in oral cavity squamous cell carcinoma.

OBJECTIVE: The aim of this study was to evaluate a multimodality approach to sentinel lymph node biopsy (SLNB) detection with lymphoscintigraphy and single-photon emission computed tomography (SPECT)/computed tomography (CT). When combined with intraoperative imaging by a portable gamma camera (PGC), improved SLNB accuracy and detection rate may result. MATERIAL AND METHODS: A total of 42 patients selected for SLNB in node-negative T1 and T2 oral squamous cell carcinoma were retrospectively analyzed. The detection protocol consisted of preoperative lymphoscintigraphy and SPECT/CT performed the day before surgery. Intraoperative sentinel lymph node (SLN) detection was done with the aid of a PGC in association with hand-held gamma probe. RESULTS: All SLN detected in the preoperative study could be harvested except for one case. A total of 131 SLN were resected. This number was higher than the SLN depicted on lymphoscintigraphy (119 SLNs) and SPECT/CT (123 SLNs). Sublingual SLNs were observed in two cases (4.76%). These SLNs were detected by SPECT/CT but not by lymphoscintigraphy. Five (3.8%) additional SLNs not previously visualized on lymphoscintigraphy or on SPECT/CT were detected intraoperatively with the aid of the PGC. Positive SLNs were detected in eight cases (19%). Micrometastases were detected in five cases (62%) and macrometastases in three cases (38%). CONCLUSION: The SLNB detection protocol described contributes to more accurate study and detection.

Traumatic pseudoaneurysm of the superficial temporal artery: case report and review of the literature.

Pseudoaneurysm of the superficial temporal artery is an uncommon complication of a blunt trauma. It usually presents as a pulsating mass in the frontotemporal area a few weeks after the injury. Doppler ultrasonography, angiography, or computed tomographic angiography can aid or confirm the diagnosis. The treatment of choice is the surgical resection of the pseudoaneurysm and ligation of the vessels. We report a case of a pseudoaneurysm of the frontal branch of the superficial temporal artery and review the literature.

Review of secondary alveolar cleft repair.

INTRODUCTION: The alveolar cleft is a bony defect that is present in 75% of the patients with cleft lip and palate. Although secondary alveolar cleft repair is commonly accepted for these patients, nowadays, controversy still remains regarding the surgical technique, the timing of the surgery, the donor site, and whether the use of allogenic materials improve the outcomes. The purpose of the present review was to evaluate the protocol, the surgical technique and the outcomes in a large population of patients with alveolar clefts that underwent secondary alveolar cleft repair. MATERIALS AND METHODS: A total of 109 procedures in 90 patients with alveolar cleft were identified retrospectively after institutional review board approval was obtained. The patients were treated at a single institution during a period of 10 years (2001-2011). Data were collected regarding demographics, type of cleft, success parameters of the procedure (oronasal fistulae closure, unification of the maxillary segments, eruption and support of anterior teeth, support to the base of the nose, normal ridge form for prosthetic rehabilitation), donor site morbidity, and complications. Pre- and postoperative radiological examination was performed by means of orthopantomogram and computed tomography (CT) scan. RESULTS: The average patient age was 14.2 years (range 4-21.3 years). There were 4 right alveolar-lip clefts, 9 left alveolar-lip clefts, 3 bilateral alveolar-lip clefts, 18 right palate-lip clefts, 40 left palate-lip clefts and 16 bilateral palate-lip clefts. All the success parameters were favorable in 87 patients. Iliac crest bone grafts were employed in all cases. There were three bone graft losses. In three cases, allogenic materials used in a first surgery performed in other centers, underwent infection and lacked consolidation. They were removed and substituted by autogenous iliac crest bone graft. CONCLUSIONS: THE USE OF AUTOGENOUS ILIAC CREST FOR SECONDARY ALVEOLAR BONE GRAFTING ACHIEVES ALL THESE SEVERAL OBJECTIVES: (1) to obtain maxillary arch continuity, (2) to maximize bone support for the dentition, (3) to stabilize the maxillary segments after orthodontic treatment, (4) to eliminate oronasal fistulae, (5) to provide nasal alar cartilage support, (6) to establish ideal alveolar morphology, and (7) to provide available bone with attached soft tissue for future endosteal implant placement in cases where there is a residual dental space. We advocate for the use of a minimal incision to obtain the iliac crest bone graft and for the use of a corticocancellous block of bone in combination with bone chips.

Lemierre Syndrome associated with dental infections. Report of one case and review of the literature

La primera publicación de Síndrome de Lemierre fue en 1936 por Lemierre. Se define como una “infección bacteriana orofaríngea que se caracteriza por la tromboflebitis de la vena yugular interna, complicándose con embolismos sépticos sistémicos”. El 81% de los casos, el agente etiológico más frecuente es Fusobacterium necrophorum. La fiebre suele ser el síntoma más frecuente, pero dependiendo de la infección primaria, ya sea amigdalitis, mastoiditis o infección odontógena. La mortalidad es muy baja según la literatura, pero con una morbilidad significativa, por eso es muy importante el diagnóstico y tratamiento precoz. El diagnóstico es clínico, aunque la TC y otros métodos diagnósticos (ecografía, RM) ayudar a determinar la extensión de la infección. Es necesaria la administración de antibióticos por vía endovenosos a dosis máxima, recordando que el microorganismo más frecuente es anaeróbico, y unas medidas de soporte vital. Presentamos un caso clínico de Síndrome de Lemierre asociado a una infección odontógena por causa del molar 4.8

The first publication on Lemierre Syndrome appears in 1936 by Lemierre. It is defined as an “oropharynx bacterial infection characterized by the thrombophlebitis in the internal jugular vein, derived in a systemic septic embolism”. In 81% of the cases, the Fusobacterium necrophorum is the most frequent etiologic agent. Fever is the most common symptom, but it can depending on the primary infection, tonsillitis, mastoiditis or odontogenic infection. According to the literature the mortality is very low, but with a significant morbidity, that is why the diagnosis and early treatment is very important. The diagnosis it´s clinical, even though the CT scan and other diagnosis methods (echography, MRI) help to determine the extent of the infection. It’s necessary to administrate the antibiotics endovenous at high dose, (keeping in mind that the most frequent micro organism is anaerobic), and vital support measures if neccessary. We present a case report of Lemierre Syndrome associated to an odonthogenic infection caused by the 4.8 molar

Tumor pardo mandibular: primera manifestación clínica de hiperparatiroidismo primario / Brown tumor of the madible: first clinical presentation of prymary hyperparathyroidism

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