Larynx preservation without jeopardizing survival appears feasible in patients with cancer of the hypopharynx. On the basis of these observations, the EORTC has now accepted the use of induction chemotherapy followed by radiation as the new standard treatment in its future phase III larynx preservation trials.

The European Laryngological Society is proposing a classification of different laryngeal endoscopic cordectomies in order to ensure better definitions of post-operative results. We chose to keep the word "cordectomy" even for partial resections because it is the term most often used in the surgical literature. The classification comprises eight types of cordectomies: a subepithelial cordectomy (type I), which is resection of the epithelium; a subligamental cordectomy (type II), which is a resection of the epithelium, Reinke's space and vocal ligament; transmuscular cordectomy (type III), which proceeds through the vocalis muscle; total cordectomy (type IV); extended cordectomy, which encompasses the contralateral vocal fold and the anterior commissure (type Va); extended cordectomy, which includes the arytenoid (type Vb); extended cordectomy, which encompasses the subglottis (type Vc); and extended cordectomy, which includes the ventricle (type Vd). Indications for performing those cordectomies may vary from surgeon to surgeon. The operations are classified according to the surgical approach used and the degree of resection in order to facilitate use of the classification in daily practice. Each surgical procedure ensures that a specimen is available for histopathological examination.

There is no evidence that one treatment was superior to the other or could improve the outcome reported with ICT followed by RT alone (French Groupe Oncologie Radiothérapie Tête et Cou [GORTEC] 2000-01 trial [Induction CT by Cisplatin, 5FU With or Without Docetaxel in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma]). The protocol that can best compare with RT alone after ICT is still to be determined.

Background: Free jejunal transfer has become the standard technique for reconstruction of the pharynx and hypopharynx, especially with proximal neoplastic lesions, whereas gastric tube interposition is the technique of choice for reconstruction of the hypopharynx and cervical esophagus when resection extends below the thoracic inlet. Hypothesis: Surgical ablation is a viable option for advanced hypopharyngeal and cervical esophageal neoplasms, with stomach interposition a safe and preferred method of reconstruction. Design: Retrospective analysis. Setting: University hospital that is a regional referral institution for esophageal cancer treatment and complex digestive reconstructions after esophagectomy. Patients: We reviewed the records of 209 patients who underwent total pharyngolaryngectomy between May 1982 and July 1999. The majority of patients had advanced cancer: hypopharyngeal in 131 cases and cervical esophageal in 78 cases. Interventions: Pharyngolaryngectomy and total esophagectomy with pharyngogastric anastomoses (n=127); pharyngolaryngectomy, cervical esophagectomy, and reconstruction with free jejunal transplant (n =77); and pharyngolaryngectomy and total esophagectomy with pharyngocolic anastomoses (n = 5). Main Outcome Measures: Postoperative mortality and morbidity, long-term survival, and prognostic factors influencing survival. Results: The postoperative in-hospital mortality rate was 4.8% (10 patients), with a postoperative morbidity rate of 38.3%. Alimentary continuity was achieved using the stomach (127 patients), colon (5 patients), or free jejunal autograft (77 patients). The 1-year and 5-year survival rates were 62% and 24%, respectively. There was no significant difference with regard to the survival between gastric transposition and free jejunal autograft, but there were fewer complications in the gastric pull-up group (33% vs 47%, PϽ.05). The significant adverse factors affecting survival were tumor cervical localization, postoperative complications, disease stages pT3 and pT4 for the cervical esophageal tumors, microscopic pharyngeal penetration, or incomplete resection. The significant beneficial factors were tumor hypopharyngeal localization and postoperative radiotherapy. Conclusions: Surgical ablation is a viable option for advanced hypopharyngeal and cervical esophageal neoplasms, with stomach interposition the preferred method of reconstruction. Although the prognosis is poor, satisfactory short-term palliation can be achieved. The significant adverse factors affecting survival should be taken into account to select the candidates for surgery.

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Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.

A classification of laryngeal endoscopic cordectomies, which included eight different types, was first proposed by the European Laryngological Society in 2000. The purpose of this proposal of classification was an attempt to reach better consensus amongst clinicians and agree on uniformity in reporting the extent and depth of resection of cordectomy procedures, to allow relevant comparisons within the literature when presenting/publishing the results of surgery, and to recommend the use of guidelines to allow for reproducibility amongst practicing laryngologists. A total of 24 article citations of this classification have been found through the science citation index, as well as 3 book chapters on larynx cancer surgery, confirming its acceptance. However, on reflection, and with the passage of time, lesions originating at the anterior commissure have not been clearly described and, for that reason, a new endoscopic cordectomy (type VI) for cancers of the anterior commissure, which have extended or not to one or both of the vocal folds, without infiltration of the thyroid cartilage is now being proposed by the European Laryngological Society Committee on Nomenclature to revise and complete the initially reported classification.

Endothelins are thought to act through two specific, plasmalemmal G protein-coupled receptor subtypes, ET A R and ET B R. However, in subfractionated cardiac membranes, ET A R immunoreactivity was detected only in the plasma membrane whereas ET B R immunoreactivity was detected predominantly in membranes of intracellular origin. Confocal microscopy demonstrated the presence of intracellular ET A R and ET B R in ventricular myocytes. ET A R were primarily on plasma membrane (surface membranes and transverse-tubules) and to a lesser extent on the nucleus while ET B R localized primarily to the nuclei. Western blot analysis of nuclei isolated from the heart indicated the presence of endothelin receptors: both ET A R and ET B R copurified with nucleoporin 62, whereas markers of endoplasmic reticulum and Golgi membranes were depleted. Endothelins are a family of 21-amino acid isopeptides (ET-1, -2, and -3), 1 derived from different genes, which mediate a wide spectrum of pharmacological activities in a variety of tissues (see Ref. 1). In the heart, ET-1 produces positive inotropic (2-4) and chronotropic (5) effects, prolongs the action potential (6, 7), and mediates cardiac remodeling in hypertrophy (4, 8 -14), myocardial infarction (15), and congestive heart failure (16, 17). To date, two mammalian endothelin receptor subtypes (ET A R and ET B R) have been cloned (18 -20). The ET A R is selective for ET-1 ϭ ET-2 Ͼ Ͼ ET-3, with sarafotoxin 6c being inactive whereas the ET B R is non-selective. Subtype-specific pharmacological antagonists also help to distinguish the two receptor subtypes. An additional endothelin receptor (ETR) subtype, ET C R, has been cloned from Xenopus laevis (21); however, a mammalian homolog has yet to be identified. Both ET A R and ET B R are seven-transmembrane spanning receptors known to couple to an overlapping array of heterotrimeric G-proteins (22) leading to activation of multiple signaling systems including phospholipase C (23-25), phospholipase D (26, 27), phospholipase A 2 (28), cytosolic Ca 2ϩ (29, 30), Na/H exchange (31), cAMP production (23), cGMP production (32), tyrosine kinases (33, 34), and mitogen-activated protein kinases (14,35,36). Both ET A R and ET B R subtypes are present in heart (18,19,(37)(38)(39); in human myocardium, ET A R and ET B R are expressed at similar levels (38).It is now thought that ET-1 may act in an autocrine/paracrine manner in the cardiac ventricular myocyte. All three endothelins are synthesized as larger precursor proteins, prepro-ETs, which are subsequently cleaved to 37-41-amino acid proforms, referred to as big endothelins. Big endothelins are converted to mature endothelins by endothelin-converting enzymes (ECE). Splice variants of the ECE-1 isoform, ECE-1a and ECE-1c, have been detected in adult cardiac myocytes (40), and ECE-1c expression is up-regulated 5-fold in myocytes during congestive heart failure (40). ET-1 is produced, stored, and secreted by neonatal (41) and adult cardiac ventricular myocytes (42) under basal conditions, and regulat...