Benoît Lengelé

First human face allograft: early report

BACKGROUND Extended soft tissue defects of the face are difficult to reconstruct, and autologous tissue transfers usually lead to poor cosmetic and functional outcomes. We judged that composite tissue transplantation could be valuable in facial reconstructive surgery. METHODS We transplanted the central and lower face of a brain-dead woman onto a woman aged 38 years who had suffered amputation of distal nose, both lips, chin, and adjacent parts of the cheeks. Transplantation consisted of revascularisation of right and left facial arteries and veins (ischaemic time 4 h), mucosal repair of oral and nasal vestibules, bilateral anastomoses of infraorbital and mental sensitive nerves, joining of mimic muscles with motor nerve suture on mandibular branch of the left facial nerve, and skin closure. Immunosuppressive treatment was with thymoglobulin, tacrolimus, mycophenolate mofetil, and prednisone. Two infusions of donor bone-marrow cells were given. Follow-up included routine tests, biopsies, physiotherapy, and psychological support. FINDINGS The initial postoperative course was uneventful. No surgical complication occurred. Bone-marrow graft and immunosuppression were well tolerated. Mild clinical signs of rejection were seen at day 20. Increased corticoids initially did not reverse rejection, but signs of rejection disappeared after three boluses of prednisone. Anatomical and psychological integration and recovery of sensation were excellent. At the end of the first postoperative week, the patient could eat, and speech improved quickly. Passive transmission of muscle contractions to the graft already exists; physiotherapy is being done to restore dynamic motions around the lips. INTERPRETATION The 4-month outcome demonstrates the feasibility of this procedure. The functional result will be assessed in the future, but this graft can already be deemed successful with respect to appearance, sensitivity, and acceptance by the patient.

Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines

In 2003, a panel of experts published a set of consensus guidelines for the delineation of the neck node levels in node negative patients (Radiother Oncol, 69: 227-36, 2003). In 2006, these guidelines were extended to include the characteristics of the node positive and the post-operative neck (Radiother Oncol, 79: 15-20, 2006). These guidelines did not fully address all nodal regions and some of the anatomic descriptions were ambiguous, thereby limiting consistent use of the recommendations. In this framework, a task force comprising opinion leaders in the field of head and neck radiation oncology from European, Asian, Australia/New Zealand and North American clinical research organizations was formed to review and update the previously published guidelines on nodal level delineation. Based on the nomenclature proposed by the American Head and Neck Society and the American Academy of Otolaryngology-Head and Neck Surgery, and in alignment with the TNM atlas for lymph nodes in the neck, 10 node groups (some being divided into several levels) were defined with a concise description of their main anatomic boundaries, the normal structures juxtaposed to these nodes, and the main tumor sites at risk for harboring metastases in those levels. Emphasis was placed on those levels not adequately considered previously (or not addressed at all); these included the lower neck (e.g. supraclavicular nodes), the scalp (e.g. retroauricular and occipital nodes), and the face (e.g. buccal and parotid nodes). Lastly, peculiarities pertaining to the node-positive and the post-operative clinical scenarios were also discussed. In conclusion, implementation of these guidelines in the daily practice of radiation oncology should contribute to the reduction of treatment variations from clinician to clinician and facilitate the conduct of multi-institutional clinical trials.

En-bloc and Standard Esophagectomies by Thoracoscopy

Subtotal esophagectomy was attempted by right thoracoscopy on 13 patients, 10 having cancer and 3 long caustic stenosis. Thoracoscopy was converted into thoracotomy in 2 patients, owing to loss of selectivity in one-lung ventilation in 1 and injury to a right intercostal artery flush to the aorta in the other. One patient with cancer underwent an esophageal bypass operation only, owing to tumor invasion into the lung at exploratory thoracoscopy. The ten esophagectomies that could be performed in totality by thoracoscopy consisted of seven en bloc resections of the esophagus with extensive lymph node clearance in the posterior mediastinum, and three standard resections without any lymph node dissection. Postoperative complications included one death due to hepatic failure, two cases of acute pneumonitis, and one persistent chest wall discomfort at the trocar sites. Up to 51 lymph nodes were found in the resected specimens of the cancer patients. Six of the 7 cancer patients who were discharged from the hospital after esophagectomy completed by thoracoscopy were alive at 2 to 20 months of follow-up. Five of them were disease free. The study shows that esophageal resections as extensive as those carried out by thoracotomy can be performed by thoracoscopy. It suggests that prompt management of untoward injury to any mediastinal structure adjacent to the esophagus is less easy by thoracoscopy than by thoracotomy, and that classic complications of open thoracic surgery may occur after thoracoscopy as well.

First human face transplantation : 5 years outcomes

Background. The first human facial allotransplantation, a 38-year-old woman, was performed on November 27, 2005. The aesthetic aspect and functional recovery and the risk-to-benefit ratio are evaluated 5 years later. Materials and Methods. The facial transplantation included nose, chin, part of cheeks, and lips. The immunosuppressive protocol included tacrolimus, mycophenolate mofetil, prednisone, and antithymocyte globulins. In addition, donor bone marrow cells were infused on days 4 and 11 after transplantation. Results. The aesthetic aspect is satisfying. The patient has normal protective and discriminative sensibility. She showed a rapid motion recovery, which has remained stable for 3 years posttransplantation. She can smile, chew, swallow, and blow normally whereas pouting and kissing is still difficult. Phonation recovery was impressive therefore the patient can talk normally. Two episodes of acute rejection developed during the first year. Donor-specific anti-human leukocyte antigen antibodies were never detected. Five-year mucosal biopsy showed a slight perivascular inflammatory infiltrate while skin biopsy was normal. The main side effect of the immunosuppressive treatment was a progressive decrease in renal function, which improved after switching from tacrolimus to sirolimus. Moreover, she developed arterial hypertension, an increase in lipid levels, and in situ cervix carcinoma treated by conization. Since 2008, she showed mild cholangitis possibly caused by sirolimus. In September 2010, bilateral pneumopathy occurred and was successfully treated with antibiotics. Conclusion. Despite some long-term complications, which are similar to those reported after solid organ transplantation, the patient is satisfied of her new face and has normal social interaction.

Targeted hypoglossal neurostimulation for obstructive sleep apnoea: a 1-year pilot study

Continuous positive airway pressure (CPAP) is an effective but cumbersome treatment for obstructive sleep apnoea (OSA). Noncompliant patients need alternative therapies. We studied a tongue neurostimulation approach: targeted hypoglossal neurostimulation (THN) therapy with the aura6000™ System. A multi-contact electrode positioned around the main trunk of the twelfth nerve connected to an implanted pulse generator stimulates segments of the nerve, activating dilator muscles. The primary objective was to improve the polysomnographically determined apnoea/hypopnoea index (AHI) at 3 months, and maintain the improvement after 12 months of treatment. 13 out of 14 operated patients were successfully implanted. At 12 months, the AHI decreased from 45±18 to 21±17, a 53% reduction (p<0.001). The 4% oxygen desaturation index fell from 29±20 to 15±16 and the arousal index from 37±13 to 25±14, both p<0.001. The Epworth sleepiness scale decreased from 11±7 to 8±4 (p=0.09). THN was neither painful nor awakened patients, who all complied with therapy. There were two transient tongue paresis. The present study represents the longest study of any hypoglossal neurostimulation reported to date. We conclude that THN is safe and effective to treat OSA in patients not compliant with CPAP.

Clinicopathologic monitoring of the skin and oral mucosa of the first human face allograft: Report on the first eight months

Background. The first human face allograft was performed in France on November 27, 2005. We report herein the clinicopathologic findings from the skin and oral mucosa of this allograft during the first eight months. Methods. Sequential biopsies were taken from the facial skin (n=3), oral mucosa (n=20), and sentinel skin graft (n=11) from day 3 to day 220 postgraft and examined (immuno)histologically, using a pathological score previously proposed for evaluation of rejection in composite tissue (hand) transplantation. Results. The patient developed clinically rejection episodes at day 20 and during the eighth month postgraft, manifesting with redness and edema of the facial skin, oral mucosa, and sentinel graft skin. Pathologically, changes suggestive of rejection grades 0, I, II, and III were seen in 1, 1, 1, and 0 biopsies of facial skin, 7, 2, 1, and 1 biopsies of sentinel skin graft and 3, 5, 8, and 4 biopsies of oral mucosa, respectively. Pathological changes were generally more severe in the oral mucosa than in facial and sentinel graft skin (mean scores 1.85, 0.64, and 1, respectively). Conclusions. As it happens with other composite tissue allografts, close clinicopathologic monitoring of the skin (and oral mucosa) seems to be the most reliable way to detect rejection in the setting of human facial tissue allotransplantation. Apart from these rejection episodes, the skin and mucosa maintained a normal microscopic structure, paralleling functional recovery.

Current Concepts and Future Challenges in Facial Transplantation

Facial allotransplantation has become a surgical reality. The first successful segmental human face transplants have demonstrated that facial allografts are reliable, their rejection can be prevented by low-dose immunosuppression, and their neurologic recovery enables oral and expressive functions of the face to be restored. Clinical facts have shown that the risk-benefit balance is acceptable in the medium term, that at the neurocognitive level the allograft is reintegrated in the body scheme of the recipient, and that it does not engender a donor identity transfer. This article presents a classification of facial allografts and discusses the technical, immunologic, and ethical challenges that lie ahead.

Anatomical bases for the radiological delineation of lymph node areas. Part III : pelvis and lower limbs

Cancer spreads locally through direct infiltration into soft tissues, or at a distance by invading vascular structures, then migrating through the lymphatic or blood flow. Although cancer cells carried in the blood can end in virtually any corner of the body, lymphatic migration is usually stepwise, through successive nodal stops, which can temporarily delay further progression. In radiotherapy, irradiation of lymphatic paths relevant to the localization of the primary has been common practice for decades. Similarly, excision of cancer is often completed by lymphatic dissection. Both in radiotherapy and in surgery, advanced knowledge of the lymphatic pathways relevant to any tumor location is an important information for treatment preparation and execution. The third part of these series describes the lymphatics of the pelvis and the lower limb. It Provides anatomical bases for the radiological delineation of lymph nodes areas in the pelvic cavity and in the groin. It also offers the first original classification for labeling the intrapelvic nodes, grouped in seven paired volumes (called levels I-VII), functionally linked with one another and lower abdominal levels by eight potential drainage pathways.

Recent insights into the cell biology of thyroid angiofollicular units.

In thyrocytes, cell polarity is of crucial importance for proper thyroid function. Many intrinsic mechanisms of self-regulation control how the key players involved in thyroid hormone (TH) biosynthesis interact in apical microvilli, so that hazardous biochemical processes may occur without detriment to the cell. In some pathological conditions, this enzymatic complex is disrupted, with some components abnormally activated into the cytoplasm, which can lead to further morphological and functional breakdown. When iodine intake is altered, autoregulatory mechanisms outside the thyrocytes are activated. They involve adjacent capillaries that, together with thyrocytes, form the angiofollicular units (AFUs) that can be considered as the functional and morphological units of the thyroid. In response to iodine shortage, a rapid expansion of the microvasculature occurs, which, in addition to nutrients and oxygen, optimizes iodide supply. These changes are triggered by angiogenic signals released from thyrocytes via a reactive oxygen species/hypoxia-inducible factor/vascular endothelial growth factor pathway. When intra- and extrathyrocyte autoregulation fails, other forms of adaptation arise, such as euthyroid goiters. From onset, goiters are morphologically and functionally heterogeneous due to the polyclonal nature of the cells, with nodules distributed around areas of quiescent AFUs containing globules of compact thyroglobulin (Tg) and surrounded by a hypotrophic microvasculature. Upon TSH stimulation, quiescent AFUs are activated with Tg globules undergoing fragmentation into soluble Tg, proteins involved in TH biosynthesis being expressed and the local microvascular network extending. Over time and depending on physiological needs, AFUs may undergo repetitive phases of high, moderate, or low cell and tissue activity, which may ultimately culminate in multinodular goiters.

Prognostic factors and assessment of staging systems for head and neck soft tissue sarcomas in adults

OBJECTIVES The primary objectives of this study were to analyse the outcome of patients diagnosed with head and neck soft tissue sarcomas (HNSTS) and to identify relevant prognostic factors. As well as this, we compared the prognostic value of two staging systems proposed by the American Joint Committee on Cancer (AJCC) and the Memorial Sloan-Kettering Cancer Center (MSKCC). METHODS From 07/1988 to 01/2008, the charts of 42 adult patients were retrospectively reviewed. Potential prognostic factors were analysed according to overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). RESULTS At 5 years, OS was 57%, DFS 47% and DSS 72%. On univariate analysis, statistically significant prognostic factors were for OS, distant or lymph node metastasis at diagnosis (p=0.032), for DFS, margins after surgery (p=0.007), for DSS, regional or distant metastasis at diagnosis (p=0.002), initial AJCC and MSKCC stage (p=0.018 and p=0.048) and margins after surgery (p=0.042). On multivariate analysis, margins remained statistically significant for DFS (p=0.039) when there was a trend with the initial AJCC stage (p=0.054) for OS. The AJCC staging system was of more prognostic value than the MSKCC staging system. CONCLUSIONS Achieving clear margins after surgery is vital for improved local control and the best chance of survival. Adjuvant chemotherapy and radiotherapy were not shown to provide additional benefit. To better identify prognostic factors, it seems essential to set up national and international databases allowing multicenter registration for those patients.