Johannes J. Fagan

Contemporary management of lymph node metastases from an unknown primary to the neck: I. A review of diagnostic approaches

In an era of advanced diagnostics, metastasis to cervical lymph nodes from an occult primary tumor is a rare clinical entity and accounts for approximately 3% of head and neck malignancies. Histologically, two thirds of cases are squamous cell carcinomas (SCCs), with other tissue types less common in the neck. With modern imaging and tissue examinations, a primary tumor initially undetected on physical examination is revealed in >50% of patients and the site of the index primary can be predicted with a high level of probability. In the present review, the range and limitations of diagnostic procedures are summarized and the optimal diagnostic workup is proposed. Initial preferred diagnostic procedures are a fine‐needle aspiration biopsy (FNAB) and imaging. This allows directed surgical biopsy (such as tonsillectomy), based on the preliminary findings, and prevents misinterpretation of postsurgical images. When no primary lesion is suggested after imaging and panendoscopy, and for patients without a history of smoking and alcohol abuse, molecular profiling of an FNAB sample for human papillomavirus (HPV) and/or Epstein–Barr virus (EBV) is important. Head Neck, 2013

Contemporary management of lymph node metastases from an unknown primary to the neck: II. a review of therapeutic options.

Although uncommon, cancer of an unknown primary (CUP) metastatic to cervical lymph nodes poses a range of dilemmas relating to optimal treatment. The ideal resolution would be a properly designed prospective randomized trial, but it is unlikely that this will ever be conducted in this group of patients. Accordingly, knowledge gained from retrospective studies and experience from treating patients with known head and neck primary tumors form the basis of therapeutic strategies in CUP. This review provides a critical appraisal of various treatment approaches described in the literature. Emerging treatment options for CUP with metastases to cervical lymph nodes are discussed in view of recent innovations in the field of head and neck oncology and suitable therapeutic strategies for particular clinical scenarios are presented. For pN1 or cN1 disease without extracapsular extension (ECE), selective neck dissection or radiotherapy offer high rates of regional control. For more advanced neck disease, intensive combined treatment is required, either a combination of neck dissection and radiotherapy, or initial (chemo)radiotherapy followed by neck dissection if a complete response is not recorded on imaging. Each of these approaches seems to be equally effective. Use of extensive bilateral neck/mucosal irradiation must be weighed against toxicity, availability of close follow‐up with elective neck imaging and guided fine‐needle aspiration biopsy (FNAB) when appropriate, the human papillomavirus (HPV) status of the tumor, and particularly against the distribution pattern (oropharynx in the majority of cases) and the emergence rate of hidden primary lesions (<10% after comprehensive workup). The addition of systemic agents is expected to yield similar improvement in outcome as has been observed for known head and neck primary tumors. Head Neck, 2013

Modern reconstruction techniques for oral and pharyngeal defects after tumor resection

Several techniques have been developed to reconstruct oral and pharyngeal defects following surgery, in order to restore function and cosmesis. These are primary closure, skin grafts, local transposition of skin, mucosa and/or muscle, regional flaps and free vascularized flaps. Because of the ‘bulky’, pedicled nature and problems with the donor area of locoregional flaps, and consequently frequently unsatisfactory functional results, free vascularized flaps have gained popularity during the last decade. The authors review the current options available to give physicians, who are not experienced in the field of reconstruction in the head and neck, an impression of the range of techniques available for reconstruction of oral and pharyngeal defects following tumor resection. For reconstruction of oral cavity and pharyngeal defects, fasciocutaneous (e.g. radial forearm and anterolateral thigh flaps) and myocutaneous free flaps (e.g. rectus abdominis and latissimus dorsi) have proven to be very reliable. Free vascularized osteocutaneous flaps (e.g. fibula and iliac crest) permit reconstructive options for bony defects of the mandible or maxilla that can be adapted to a variety of defects. Depending on the site, size and involved tissues of the surgical defect and patient factors, a variety of reconstructive options are available. For both soft tissue and bony defects of the upper aerodigestive tract, microvascular free flaps provide good functional outcomes.

Management of the orbit in malignant sinonasal tumors

Malignant ethmoid and maxillary sinus tumors frequently involve the orbit. Orbital involvement is an important prognostic predictor of recurrence‐free, disease‐specific, and overall survival. Most authors agree that orbital preservation as opposed to orbital exenteration or clearance does not result in significant differences in local recurrence or actuarial survival. The eye can be safely preserved in most patients with ethmoid or maxillary sinus cancer invading the orbital wall, including malignancies that invade the orbital soft tissues with penetration through the periorbita provided that they can be completely dissected away from the orbital fat. Malposition of the globe and nonfunctional eyes frequently result when patients have not had adequate rigid reconstruction of the orbital floor, particularly if they have received postoperative radiotherapy. This underscores the importance of such reconstruction. Isolated defects following orbital exenteration may be reconstructed with a temporalis muscle flap. Microvascular free‐tissue transfer is the best option for repair of defects following orbital exenteration and total maxillectomy, although an obturator still has a role in selected patients.

Transoral laser surgery for supraglottic cancer.

The goal of treatment for supraglottic cancer is to achieve cure and to preserve laryngeal function. Organ preservation strategies include both endoscopic and open surgical approaches as well as radiation and chemotherapy. The challenge is to select the correct modalities for each patient. Endoscopic procedures should be limited to tumors that can be completely visualized during diagnostic microlaryngoscopy. If complete resection can be achieved, the oncologic results of transoral laser surgery appear to be comparable to those of classic supraglottic laryngectomy. In addition, functional results of transoral laser resection are superior to those of the conventional open approach, in terms of the time required to restore swallowing, tracheotomy rate, incidence of pharyngocutaneous fistulae, and shorter hospital stay. The management of the neck remains of paramount importance, as survival of patients with supraglottic cancer depends more on cervical metastasis than on the primary tumor. Most authors advocate bilateral elective neck dissection. However, in selected cases (T1,T2 clinically negative [N0] lateral supraglottic cancers), ipsilateral selective neck dissection could be performed without compromising survival. The authors conclude that with careful selection of patients, laser supraglottic laryngectomy is a suitable, and often the preferred, treatment option for supraglottic cancer.

Vascularized tissue to reduce fistula following salvage total laryngectomy: a systematic review.

Pharyngocutaneous fistulae (PCF) are known to occur in nearly one‐third of patients after salvage total laryngectomy (STL). PCF has severe impact on duration of admission and costs and quality of life and can even cause severe complications such as bleeding, infection and death. Many patients need further surgical procedures. The implications for functional outcome and survival are less clear. Several studies have shown that using vascularized tissue from outside the radiation field reduces the risk of PCFs following STL. This review and meta‐analysis aims to identify the evidence base to support this hypothesis.

Proposal for A Rational Classification of Neck Dissections

Alfio Ferlito, MD, DLO, DPath, FRCSEd ad hominem, FRCS (Eng, Glasg, Ir) ad eundem, FDSRCS ad eundem, FHKCORL, FRCPath, FASCP, IFCAP, K. Thomas Robbins, MD, FRCSC, Jatin P. Shah, MD, PhD (Hon), MS, FRCSEd (Hon), FRACS (Hon), FDSRCS, Jesus E. Medina, MD, Carl E. Silver, MD, Shawkat Al-Tamimi, MD, Johannes J. Fagan, MBChB, FCS (SA) MMed, Vinidh Paleri, MS, FRCS (ORL-HNS), Robert P. Takes, MD, PhD, Carol R. Bradford, MD, Kenneth O. Devaney, MD, JD, FCAP, Sandro J. Stoeckli, MD, Randal S. Weber, MD, Patrick J. Bradley, MB, BCh, BAO, DCH, MBA, FRCS (Ed, Eng, Ir), FHKCORL, FRCSLT (Hon), FRACS (Hon), Carlos Suarez, MD, PhD, C. Rene Leemans, MD, PhD, H. Hakan Coskun, MD, Karen T. Pitman, MD, Ashok R. Shaha, MD, Remco de Bree, MD, PhD, Dana M. Hartl, MD, PhD, Missak Haigentz, Jr, MD, Juan P. Rodrigo, MD, PhD, Marc Hamoir, MD, Avi Khafif, MD, Johannes A. Langendijk, MD, PhD, Randall P. Owen, MD, MS, Alvaro Sanabria, MD, MSc, PhD, Primož Strojan, MD, PhD, Vincent Vander Poorten, MD, PhD, Jochen A. Werner, MD, Stanislaw Bien, MD, PhD, Julia A. Woolgar, FRCPath, PhD, Peter Zbaren, MD, Jan Betka, MD, PhD, FCMA, Benedikt J. Folz, MD, Eric M. Genden, MD, Yoav P. Talmi, MD, Marshall Strome, MD, MS, Jesus Herranz Gonzalez Botas, MD, Jan Olofsson, MD, Luiz P. Kowalski, MD, PhD, Jon D. Holmes, DMD, MD, Yasuo Hisa, MD, PhD, Alessandra Rinaldo, MD, FRCSEd ad hominem, FRCS (Eng, Ir) ad eundem, FRCSGlasg

Cutaneous head and neck basal and squamous cell carcinomas with perineural invasion.

Perineural invasion (PNI) occurs in 2% to 6% of cutaneous head and neck basal and squamous cell carcinomas (SCCs) and is associated with mid-face location, recurrent tumors, high histologic grade, and increasing tumor size. Patients may be asymptomatic with PNI appreciated on pathologic examination of the surgical specimen (microscopic), or may present with cranial nerve (CN) deficits (clinical). The V and VII CNs are most commonly involved. Magnetic resonance imaging (MRI) may be obtained to detect and define the extent of PNI; computed tomography (CT) or ultrasound-guided fine needle aspiration cytology (UGFNAC) may assist with detecting or excluding regional lymph node metastases. Patients with apparently resectable cancers undergo surgery, usually followed by postoperative radiotherapy (RT). Patients with unresectable cancers are treated with definitive RT. Moreover, RT may be considered if significant functional or cosmetic impairment is expected after surgical treatment. The 5-year outcomes after treatment for clinically unsuspected microscopic compared with clinical PNI are: local control, 80% and 55%; cause-specific survival, 75% and 65%; and overall survival, 55% and 50%, respectively. The incidence of grade ≥ 3 complications is higher after treatment for clinical PNI versus microscopic PNI; approximately 35% compared with 15%, respectively. Proton beam RT may be used to reduce the risk of late complications by reducing RT dose to the visual apparatus and central nervous system (CNS).

Recent changes in the treatment of patients with advanced laryngeal cancer.

Since the original data from the Department of Veterans Affairs Laryngeal Cancer Study Group demonstrated that nonsurgical therapy could achieve survival rates comparable to total laryngectomy in selected cases, there has been a progressive increase in employment of nonsurgical therapy for the management of advanced laryngeal cancer. Both neoadjuvant chemotherapy followed by conventionally fractionated or hyperfractioned radiotherapy for chemotherapy responders, or simultaneously administered chemoradiation has resulted in a significant number of patients who achieved cure while preserving their larynges. Nevertheless, combined chemotherapy and external beam radiation is associated with a variety of acute and chronic sequelae that can have a debilitating impact on function and quality of life. Although no therapeutic option is without risk, the decision regarding the modality of therapy for a patient with advanced laryngeal cancer should prompt a careful review of the current surgical techniques available for treatment. Data on quality of life and aging, as well as advances in minimally invasive surgical techniques, are available today that were not available at the time of the Veterans study. Selection of optimal therapy is often complex and raises the question whether the pendulum may have swung too far in the direction of nonsurgical therapy for advanced laryngeal cancer. This article reviews the current options available for a patient with advanced laryngeal cancer and discusses the impact of therapy.

Aminoglycoside: induced hearing loss in HIV-positive and HIV-negative multidrug-resistant tuberculosis patients

Background. Ototoxicity following aminoglycoside treatment for multidrug-resistant tuberculosis (MDR-TB) is a significant problem. This study documents the incidence of ototoxicity in HIV-positive and HIV-negative patients with MDR-TB and presents clinical guidelines relating to ototoxicity. Methods. A prospective cohort study of 153 MDR-TB patients with normal hearing and middle ear status at baseline controlling for 6 mitochondrial mutations associated with aminoglycoside-related ototoxicity, at Brooklyn Chest Hospital in Cape Town. Pure tone audiometry was performed monthly for 3 months to determine hearing loss. HIV status was recorded, as was the presence of 6 mutations in the MT-RNR1 gene. Results. Fifty-seven per cent developed high-frequency hearing loss. HIV-positive patients (70%) were more likely to develop hearing loss than HIV-negative patients (42%). Of 115 patients who were genetically screened, none had MT-RNR1 mutations. Conclusion. Ototoxic hearing loss is common in MDR-TB patients treated with aminoglycosides. HIV-positive patients are at increased risk of ototoxicity. Auditory monitoring and auditory rehabilitation should be an integral part of the package of care of MDR-TB patients.