Gene deletion of Corynespora cassiicola cassiicolin Cas1 suppresses virulence in the rubber tree.

Corynespora cassiicola is an ascomycete fungus causing important damages in a wide range of plant hosts, including rubber tree. The small secreted protein cassiicolin is suspected to play a role in the onset of the disease in rubber tree, based on toxicity and gene expression profiles. However, its exact contribution to virulence, compared to other putative effectors, remains unclear. We created a deletion mutant targeting the cassiicolin gene Cas1 from the highly aggressive isolate CCP. Wild-type CCP and mutant ccpΔcas1 did not differ in terms of mycelium growth, sporulation, and germination rate in vitro. Cas1 gene deletion induced a complete loss of virulence on the susceptible clones PB260 and IRCA631, as revealed by inoculation experiments on intact (non-detached) leaves. However, residual symptoms persisted when inoculations were conducted on detached leaves, notably with longer incubation times. Complementation with exogenous cassiicolin restored the mutant capacity to colonize the leaf tissues. We also compared the toxicity of CCP and ccpΔcas1 culture filtrates, through electrolyte leakage measurements on abraded detached leaves, over a range of clones as well as an F1 population derived from the cross between the clones PB260 (susceptible) and RRIM600 (tolerant). On average, filtrate toxicity was lower but not fully suppressed in ccpΔcas1 compared to CCP, with clone-dependent variations. The two QTL, previously found associated with sensitivity to CPP filtrate or to the purified cassiicolin, were no longer detected with the mutant filtrate, while new QTL were revealed. Our results demonstrate that: (1) cassiicolin is a necrotrophic effector conferring virulence to the CCP isolate in susceptible rubber clones and (2) other effectors produced by CCP contribute to residual filtrate toxicity and virulence in senescing/wounded tissues. These other effectors may be involved in saprotrophy rather than necrotrophy.

QTL detection for growth and latex production in a full-sib rubber tree population cultivated under suboptimal climate conditions.

BACKGROUND: Rubber tree is cultivated in mainly Southeast Asia and is by far the most significant source of natural rubber production worldwide. However, the genetic architecture underlying the primary agronomic traits of this crop has not been widely characterized. This study aimed to identify quantitative trait loci (QTLs) associated with growth and latex production using a biparental population established in suboptimal growth conditions in Brazil. RESULTS: A full-sib population composed of 251 individuals was developed from crossing two high-producing Asiatic rubber tree cultivars, PR 255 and PB 217. This mapping population was genotyped with microsatellite markers from enriched genomic libraries or transcriptome datasets and single-nucleotide polymorphism (SNP) markers, leading to construction of a saturated multipoint integrated genetic map containing 354 microsatellite and 151 SNP markers. Height and circumference measurements repeated over a six-year period and registration of cumulative latex production during six consecutive months on the same individuals allowed in-depth characterization of the genetic values of several growth traits and precocious latex production. Growth traits, circumference and height, were overall positively correlated, whereas latex production was not correlated or even negatively correlated with growth traits. A total of 86 distinct QTLs were identified, most of which were detected for only one trait. Among these QTLs, 15 were linked to more than one phenotypic trait (up to 4 traits simultaneously). Latex production and circumference increments during the last wintering period were associated with the highest numbers of identified QTLs (eleven and nine, respectively), jointly explaining the most significantly observed phenotypic variances (44.1% and 44.4%, respectively). The most important QTL for latex production, located on linkage group 16, had an additive effect of the male parent PB 217 and corresponded to a QTL at the same position detected in a previous study carried out in Thailand for the biparental population RRIM 600 x PB 217. CONCLUSIONS: Our results identified a set of significant QTLs for rubber tree, showing that the performance of modern Asiatic cultivars can still be improved and paving the way for further marker-assisted selection, which could accelerate breeding programs.

Postoperative hemorrhage after transoral oropharyngectomy for cancer of the lateral oropharynx.

OBJECTIVE: Assessment of incidence, risk factors, management, and outcome of postoperative hemorrhage after transoral oropharyngectomy for cancer of the lateral oropharynx. METHODS: Retrospective review of a cohort of 514 cancers of the lateral oropharynx consecutively resected. RESULTS: Incidence of postoperative hemorrhage was 3.6%. In 31.5% of cases, onset was after hospital discharge. No hemorrhages occurred after the end of the fourth postoperative week. Variables associated with increased risk of hemorrhage were advanced age (P=.004), antithrombotic treatment (P=.012), and robotic assistance (P=.009). When the source of hemorrhage could be identified, hemostasis, performed transorally in most cases, was highly effective; no patients in this subgroup showed recurrence. In spontaneously resolved hemorrhage under observation or when no active site of bleeding was found on exploration under general anesthesia, the recurrence rate was 18.1%. Overall, hemorrhage resulted in death in 2 patients. CONCLUSION: Exploration under general anesthesia in case of active bleeding and observation with discussion of arterial exploration of the ipsilateral external carotid system in patients in whom no source of bleeding can be identified are the keys to successful management of this potentially lethal complication.

De novo transcriptome analysis of Hevea brasiliensis tissues by RNA-seq and screening for molecular markers.

BACKGROUND: The rubber tree, Hevea brasiliensis, is a species native to the Brazilian Amazon region and it supplies almost all the world's natural rubber, a strategic raw material for a variety of products. One of the major challenges for developing rubber tree plantations is adapting the plant to biotic and abiotic stress. Transcriptome analysis is one of the main approaches for identifying the complete set of active genes in a cell or tissue for a specific developmental stage or physiological condition. RESULTS: Here, we report on the sequencing, assembling, annotation and screening for molecular markers from a pool of H. brasiliensis tissues. A total of 17,166 contigs were successfully annotated. Then, 2,191 Single Nucleotide Variation (SNV) and 1.397 Simple Sequence Repeat (SSR) loci were discriminated from the sequences. From 306 putative, mainly non-synonymous SNVs located in CDS sequences, 191 were checked for their ability to characterize 23 Hevea genotypes by an allele-specific amplification technology. For 172 (90%), the nucleotide variation at the predicted genomic location was confirmed, thus validating the different steps from sequencing to the in silico detection of the SNVs. CONCLUSIONS: This is the first study of the H. brasiliensis transcriptome, covering a wide range of tissues and organs, leading to the production of the first developed SNP markers. This process could be amplified to a larger set of in silico detected SNVs in expressed genes in order to increase the marker density in available and future genetic maps. The results obtained in this study will contribute to the H. brasiliensis genetic breeding program focused on improving of disease resistance and latex yield.

Ten-Year Efficacy of Transoral Surgery for Squamous Carcinoma of the Lateral Oropharynx.

OBJECTIVES: To document the 10-year results of transoral mandibular preservation surgery for patients with T1-2 squamous cell carcinoma (SCC) arising from the lateral oropharynx. METHODS: This was a retrospective 30-year review using STROBE guidelines at an academic, tertiary referral center. A total of 294 patients with T1-2 SCC of the lateral oropharynx were reviewed. Only 19% of patients were never-smokers, suggesting a predominantly HPV-negative population. All patients had transoral mandibular preservation surgery. Follow-up therapy included neck dissection (76.5%), induction chemotherapy (57.8%), and postoperative radiation therapy (31.6%) Local control, survival, and functional endpoints, as well as the consequences of local recurrence, were analyzed. RESULTS: The 10-year local disease control was 88.3%. Local recurrence was salvaged in 50% of cases, resulting in an overall 94.5% local control rate. The overall 10-year survival was 50%. Mortality was related to metachronous second primary cancer (MSPC) (29.2%), medical comorbidities (25.7%), uncontrolled local recurrence (10%), and complications following transoral resection (4.2%). In multivariate analysis, the development of an MSPC significantly increased (p < 0.005) the risk of death. Overall, 95.2% of patients achieved mandibular preservation. However, gastrostomy and tracheostomy dependence occurred in 1% and 0.3% of cases, respectively. CONCLUSIONS: For a patient population with a significant percentage of tobacco-associated oropharyngeal cancer (OPC), transoral surgery was associated with long-term minimal postoperative complications and a high rate of local control. MSPC was the main cause of death during the first 10 postoperative years. Such long-term figures support transoral surgery as an effective first-line treatment for early-stage predominantly tobacco-related OPC. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Primary Total Laryngectomy for Endolaryngeal cT3-4M0 Squamous Cell Carcinoma: A STROBE Analysis.

OBJECTIVES: To document 10-year oncologic outcome of primary total laryngectomy (TL) for patients with cT3-4M0 endolaryngeal squamous cell carcinoma (SCC). STUDY DESIGN: Observational inception cohort of 531 patients with isolated untreated endolaryngeal cT3-4M0 SCC review over 40 years using STROBE guideline. 94% of patients were followed until death or for a minimum of 10 years. SETTING: Academic tertiary referral care center. METHODS: All patients underwent primary TL. Prior tracheotomy, induction chemotherapy, thyroid gland resection, level II-IV neck dissection, level VI dissection, and postoperative radiation therapy were associated in 6%, 40%, 43%, 89%, 47%, and 74% of cases, respectively: The main objective was to determine the 10-year actuarial local control estimate. Accessory objectives comprised screening for clinical variables increasing the risk of local recurrence, and analysis of long-term oncologic consequences of local recurrence. RESULTS: The 10-year actuarial local control estimate was 89.7%. Local recurrence was salvaged in 11% of cases, resulting in 92% overall local control. On multivariate analysis, none of the study variables correlated with local recurrence. Local recurrence resulted in significantly reduced nodal control, distant metastasis control, and survival. Postoperative complications, persistent index SCC, intercurrent disease, and metachronous second primary cancer accounted for respectively 3%, 37%, 33%, and 28% of the 334 deaths noted during the 10 years following TL. CONCLUSION: The present study underscored the long-term oncologic efficacy of primary TL, the dangers of local recurrence, the key role of local control for survival, and the importance of a long-term oncologic watch policy. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2288-2294, 2024.

[Evolution of laryngectomy based on a comparison of two cohorts a century apart: an illustration of the progress, difficulties and conflicts encountered in medicine]. / Histoire des laryngectomies illustrée par l'analyse de deux cohortes à un siècle de distance : un reflet du progrès, des difficultés et des conflits rencontrés en médecine.

Based on a comparison of two cohorts of patients with laryngeal cancer managed by laryngectomy one century apart, and an analysis of original textbooks from the end of the nineteenth century, we examine the development of laryngectomy, the difficulties encountered in this first therapeutic approach to laryngeal carcinoma, and the conflicts it generated. The overall death rate changed little over the course of a century, although the 5-year actuarial survival estimate improved from 22.6% in 1888 to 75.1% in 1988 (p < .0001). The causes of death also changed (p < .0001), with fewer deaths related to post-operative complications and/or local failure (82.7% in 1888, 9% in 1988). The rate of suicide deaths fell from 1.8% to 0.04%. In contrast, the percentage of deaths due to metachronous second primary tumors and/or intercurrent disease increased from 9% in 1888 to 76.7% in 1998. Analysis of actuarial survival rates demonstrated that 77.4% of patients died before the 60th post-operative month in 1888, while this percentage was only reached 275 months post-operatively a century later. Our research also underscores the importance of patient information and medical ethics.

Transcriptome profiling in susceptible and tolerant rubber tree clones in response to cassiicolin Cas1, a necrotrophic effector from Corynespora cassiicola.

Corynespora cassiicola, a fungal plant pathogen with a large host range, causes important damages in rubber tree (Hevea brasiliensis), in Asia and Africa. A small secreted protein named cassiicolin was previously identified as a necrotrophic effector required for the virulence of C. cassiicola in specific rubber tree clones. The objective of this study was to decipher the cassiicolin-mediated molecular mechanisms involved in this compatible interaction. We comparatively analyzed the RNA-Seq transcriptomic profiles of leaves treated or not with the purified cassiicolin Cas1, in two rubber clones: PB260 (susceptible) and RRIM600 (tolerant). The reads were mapped against a synthetic transcriptome composed of all available transcriptomic references from the two clones. Genes differentially expressed in response to cassiicolin Cas1 were identified, in each clone, at two different time-points. After de novo annotation of the synthetic transcriptome, we analyzed GO enrichment of the differentially expressed genes in order to elucidate the main functional pathways impacted by cassiicolin. Cassiicolin induced qualitatively similar transcriptional modifications in both the susceptible and the tolerant clones, with a strong negative impact on photosynthesis, and the activation of defense responses via redox signaling, production of pathogenesis-related protein, or activation of the secondary metabolism. In the tolerant clone, transcriptional reprogramming occurred earlier but remained moderate. By contrast, the susceptible clone displayed a late but huge transcriptional burst, characterized by massive induction of phosphorylation events and all the features of a hypersensitive response. These results confirm that cassiicolin Cas1 is a necrotrophic effector triggering a hypersensitive response in susceptible rubber clones, in agreement with the necrotrophic-effector-triggered susceptibility model.

Extended lateral pharyngotomy for selected squamous cell carcinomas of the lateral tongue base.

OBJECTIVES: In a retrospective review of an inception cohort of 26 patients with an isolated, previously untreated, moderately to well-differentiated invasive squamous cell carcinoma of the lateral tongue base, consecutively managed with an extended lateral pharyngotomy approach at a single tertiary referral care center, the authors review the key surgical points, highlight the potential technical pitfalls, and document the complications and long-term functional and oncological outcomes in terms of survival and local control. METHODS: The adjunctive measures included induction chemotherapy, ipsilateral neck dissection, and postoperative radiotherapy, used in 96.1%, 96.1%, and 38.5% of patients, respectively. All patients but 2 were followed for at least 5 years or until death (maximum, 158 months). RESULTS: The significant postoperative complications included pharyngocutaneous fistula in 3 patients (11.5%) and hemorrhage requiring reoperation, partial flap necrosis, and pneumonia from aspiration in 1 patient (3.8%) each. In univariate analysis, no significant statistical relationship was noted between the significant postoperative complications noted and the variables under analysis. Overall, successful oral alimentation was achieved in 100% of patients by the first postoperative month without gastrostomy, tracheotomy, or completion total laryngectomy. There were no intraoperative or perioperative deaths. The main causes of death were metachronous second primary tumor, intercurrent disease, and distant metastasis, resulting in 84.6%, 64%, and 46.9% 1-, 3-, and 5-year Kaplan-Meier actuarial survival estimates, respectively. Two patients (7.6%) had local recurrence, resulting in 100%, 86.7%, and 86.7% 1-, 3-, and 5-year Kaplan-Meier actuarial local control estimates, respectively. As a function of T stage, the 3- and 5-year actuarial local control estimates were 100%, 87.5%, and 90.9% in patients with tumors classified as T1, T2, and T3-T4a, respectively. CONCLUSIONS: Such results suggest that extended lateral pharyngotomy should be integrated among the various conservative treatment options available to patients with selected carcinomas of the lateral tongue base.

Phylogenetic Origin of Primary and Secondary Metabolic Pathway Genes Revealed by C. maxima and C. reticulata Diagnostic SNPs.

Modern cultivated Citrus species and varieties result from interspecific hybridization between four ancestral taxa. Among them, Citrus maxima and Citrus reticulata, closely associated with the pummelo and mandarin horticultural groups, respectively, were particularly important as the progenitors of sour and sweet oranges (Citrus aurantium and Citrus sinensis), grapefruits (Citrus paradisi), and hybrid types resulting from modern breeding programs (tangors, tangelos, and orangelos). The differentiation between the four ancestral taxa and the phylogenomic structure of modern varieties widely drive the phenotypic diversity's organization. In particular, strong phenotypic differences exist in the coloration and sweetness and represent important criteria for breeders. In this context, focusing on the genes of the sugar, carotenoid, and chlorophyll biosynthesis pathways, the aim of this work was to develop a set of diagnostic single-nucleotide polymorphism (SNP) markers to distinguish the ancestral haplotypes of C. maxima and C. reticulata and to provide information at the intraspecific diversity level (within C. reticulata or C. maxima). In silico analysis allowed the identification of 3,347 SNPs from selected genes. Among them, 1,024 were detected as potential differentiation markers between C. reticulata and C. maxima. A total of 115 SNPs were successfully developed using a competitive PCR technology. Their transferability among all Citrus species and the true citrus genera was very good, with only 0.87% of missing data. The ancestral alleles of the SNPs were identified, and we validated the usefulness of the developed markers for tracing the ancestral haplotype in large germplasm collections and sexually recombined progeny issued from the C. reticulata/C. maxima admixture gene pool. These markers will pave the way for targeted association studies based on ancestral haplotypes.

Sternocleidomastoid myofascial flap for reconstruction after composite resection of invasive squamous cell carcinoma of the tonsillar region: technique and outcome.

OBJECTIVE: To present the surgical technique and determine the efficacy of sternocleidomastoid myofascial (SCMF) flap reconstruction after composite resection with intent to cure. STUDY DESIGN: Retrospective review of 73 consecutive patients with a previously isolated and untreated moderately to well-differentiated invasive squamous cell carcinoma of the tonsillar region and a minimum of 3 years follow-up, managed at a tertiary referral care center during the years 1970 to 2002, with an ipsilateral superiorly based SCMF flap after composite resection. METHODS: The surgical procedure is presented in detail. Potential technical pitfalls are highlighted. Survival, mortality, and morbidity are documented. Univariate analysis for potential correlation between the incidence for postoperative flap complications and various variables is also performed. RESULTS: The 1, 3, and 5 year Kaplan-Meier actuarial survival estimates were 82.2%, 64.4%, and 49.3%, respectively. Death never appeared to be related to the completion of the SCMF flap. Thirty-three (45.2%) patients had some kind of significant postoperative surgical complication, and nine (12.3%) patients had some kind of significant postoperative medical complication. The most common significant postoperative complication was partial SCMF flap necrosis and pharyngocutaneous fistula noted in 30.1% and 10.9% of patients, respectively. Complete SCMF flap necrosis was never encountered. No patient developed carotid artery rupture or died as a result of the SCMF flap, and none required additional surgery. In univariate analysis, no significant statistical relation was noted between the significant postoperative surgical complications related to the use of the SCMF flap and the variables under analysis. CONCLUSIONS: The superiorly based SCMF flap appears to be simple to perform and useful for reconstruction of defects after composite resection.

Expression analysis of ROS producing and scavenging enzyme-encoding genes in rubber tree infected by Pseudocercospora ulei.

South American Leaf Blight (SALB), caused by the ascomycete Pseudocercospora ulei, is responsible for the low productivity of rubber trees in Latin America and is a serious threat to rubber plantations in Asia and Africa, where the rubber trees are derived from highly susceptible clones. Three contrasted genotypes were chosen for their levels of resistance to the pathogen: FX2784 (totally resistant), MDF180 (partially resistant) and PB314 (susceptible). Array analyses were previously performed to identify genes differentially expressed in resistant and susceptible genotypes. Twenty-one genes were selected for further gene expression analysis in non-inoculated and inoculated genotypes from 24 to 216 h post infection (hpi). These genes are involved in ROS production (HbRBOHA, HbRBOHB, HbRBOHC, HbRBOHD), ROS-scavenging systems (cytoplasmic and chloroplastic HbCuZnSOD, HbMnSOD, HbCAT, HbAPX1, HbAPX2, HbMDHAR, HbGCL1, HbGCL2, HbOASTL, HbGPX, HbDHAR), and leaf senescence (HbCASP, HbPCYST, HbWRKY2, HbPLY, HbKAT2). First, a genotype-dependent level of expression was observed. The genes HbRBOHA, HbCuZnSOD cyto, HbCAT, HbGCL and HbWRKY2 were constitutively expressed at lower levels in the MDF180 genotype than in the FX2784 and PB314 genotypes. Conversely, the levels of expression of HbDHAR, HbGPX and HbPCYST were higher in the older, non-inoculated leaves of MDF180. Lower production of ROS and efficient regeneration of reduced ascorbate ensure a balanced redox intracellular state in this genotype. Second, inoculation of the leaves induced few modifications in the expression level of the studied genes. In the MDF180 partially resistant genotype, an increase in the expression level of HbRBOHB, HbRBOHD 48 hpi and a decrease in the expression level of HbDHAR 216 hpi were observed. In the FX2784 totally resistant genotype, an increase in the expression level of HbRBOHD and HbCuZnSOD cyto and a decrease in HbCAT were observed 48 hpi. This transitory variation could be associated with the oxidative burst classically observed in hypersensitive response (HR). The increase in the synthesis of reduced glutathione in this genotype could ensure redox balance and consequently cell homeostasis. In the PB314 susceptible genotype, HbROHC, HbCuZnSOD chloro was up-regulated 216 hpi concomitantly with a decrease in the expression level of HbCAT, consequently causing an accumulation of H2O2 and programmed cell death. The level of expression of a transcription factor, HbWRKY2, was also modulated by the P. ulei infection with early transient up-regulation in the FX2784 totally resistant genotype and permanent up-regulation in the MDF180 partially resistant genotype. These results complement studies on genetic determinism of SALB resistance and a recent publication on Hevea glutathione reductase gene.

Genetic Determinism of Sensitivity to Corynespora cassiicola Exudates in Rubber Tree (Hevea brasiliensis).

An indirect phenotyping method was developed in order to estimate the susceptibility of rubber tree clonal varieties to Corynespora Leaf Fall (CLF) disease caused by the ascomycete Corynespora cassiicola. This method consists in quantifying the impact of fungal exudates on detached leaves by measuring the induced electrolyte leakage (EL%). The tested exudates were either crude culture filtrates from diverse C. cassiicola isolates or the purified cassiicolin (Cas1), a small secreted effector protein produced by the aggressive isolate CCP. The test was found to be quantitative, with the EL% response proportional to toxin concentration. For eight clones tested with two aggressive isolates, the EL% response to the filtrates positively correlated to the response induced by conidial inoculation. The toxicity test applied to 18 clones using 13 toxinic treatments evidenced an important variability among clones and treatments, with a significant additional clone x treatment interaction effect. A genetic linkage map was built using 306 microsatellite markers, from the F1 population of the PB260 x RRIM600 family. Phenotyping of the population for sensitivity to the purified Cas1 effector and to culture filtrates from seven C. cassiicola isolates revealed a polygenic determinism, with six QTL detected on five chromosomes and percentages of explained phenotypic variance varying from 11 to 17%. Two common QTL were identified for the CCP filtrate and the purified cassiicolin, suggesting that Cas1 may be the main effector of CCP filtrate toxicity. The CCP filtrate clearly contrasted with all other filtrates. The toxicity test based on Electrolyte Leakage Measurement offers the opportunity to assess the sensitivity of rubber genotypes to C. cassiicola exudates or purified effectors for genetic investigations and early selection, without risk of spreading the fungus in plantations. However, the power of this test for predicting field susceptibility of rubber clones to CLF will have to be further investigated.

Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region: I. Technique, complications, and functional results.

OBJECTIVES: To describe the surgical technique for transoral lateral oropharyngectomy (TLO) and its safety, postoperative management, complications, and functional outcomes. DESIGN: A 20-year retrospective case series review. Mean follow-up was 10 years. All but 10 patients were followed up until the fifth postoperative year or death. SETTING: Academic, tertiary referral center. PATIENTS: A total of 191 patients who underwent TLO for selected invasive squamous cell carcinoma of the tonsil and/or tonsillar fossa. INTERVENTIONS: Ten patients had received preoperative radiation therapy. Induction chemotherapy was used in 153 patients (80.3%). An associated neck dissection was performed in 148 patients (77.5%). Postoperative radiation therapy was administered to 52 patients (28.7%). MAIN OUTCOME MEASURES: Overall survival rate, intraoperative mortality, and perioperative mortality were determined. The need for and length of nasogastric tube feeding and tracheotomy were calculated. The incidence of significant postoperative surgical and medical complications was recorded. RESULTS: No intraoperative mortality occurred, but 5 patients (2.6%) died in the immediate postoperative period, 3 from medical complications and 2 from unknown causes. In this series, the internal carotid artery was never injured, and no cutaneous-oropharyngeal fistulas were apparent. The incidence of significant surgical complications from the oropharynx was 6.3%. Nasopharyngeal reflux and severe rhinolalia were the most common complications, occurring in 9 patients. Increasing tobacco use was statistically correlated with an increase in postoperative pneumonia from aspiration (P = .05) but no surgical complications. Seven patients (3.7%) had a temporary tracheotomy for a mean of 5 days. One hundred twelve patients (58.6%) had a nasogastric tube inserted for a mean of 6 days. No patients had a permanent gastrostomy or tracheotomy tube. The mean duration of hospitalization was 9 days. The duration of hospitalization was statistically correlated with the need for nasogastric tube placement and its duration (P<.001) or tracheotomy (P<.001). CONCLUSIONS: From a functional standpoint, the TLO is a safe surgical approach for treating selected carcinoma of the tonsillar fossa. It is a reliable technique that should be considered for treatment of appropriate squamous cell carcinoma of the tonsil.

Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region: II. An analysis of the incidence, related variables, and consequences of local recurrence.

OBJECTIVES: To determine the incidence of local and regional failure, distant metastasis, and overall survival following transoral lateral oropharyngectomy (TLO) and to determine factors associated with local recurrence. DESIGN: Retrospective case series throughout 20 years; mean follow-up of 10 years. SETTING: Academic center. PATIENTS: A total of 166 previously untreated patients with squamous cell carcinoma of the tonsil. INTERVENTIONS: A total of 131 (81.9%) of the 166 patients received preoperative induction chemotherapy. Fifty-one patients (30.7%) underwent postoperative radiation therapy. MAIN OUTCOME MEASURES: Local and regional recurrence, distant metastasis, second primary tumors, and survival. RESULTS: The 1- and 5-year Kaplan-Meier local control estimates were 91.2% and 82.1%, respectively. The 1- and 5-year Kaplan-Meier local control estimates were 98.3% and 89.0% for T1, 88.9% and 81.7% for T2, and 78.9% and 62.7% for T3 lesions, respectively (P = .02). In univariate analysis, 7 variables were significantly associated with an increased risk of local failure: increasing T classification; positive margins of resection; poor clinical response to induction chemotherapy; tumor spread to the posterior pillar, posterior pharyngeal wall, and contralateral soft palate; and invasion of the junction between the tonsil and soft palate. In a logistic regression model, spread to the posterior pillar was the only variable statistically associated with local failure (P = .02). The 1-, 3-, and 5-year Kaplan-Meier survival estimates were 87.9%, 67.2%, and 57.7%, respectively. The Kaplan-Meier survival estimate was significantly reduced (P = .009) in patients with local failure. CONCLUSIONS: Selected tonsillar squamous cell carcinoma can be managed with TLO with local control comparable to radiotherapy. Patient selection is critical and TLO is best suited for patients with anterior T1 to T2 squamous cell carcinoma of the tonsil, without posterior anatomic spread.

Supracricoid hemilaryngopharyngectomy in patients with invasive squamous cell carcinoma of the pyriform sinus. Part I: Technique, complications, and long-term functional outcome.

On the basis of a retrospective review of an inception cohort of 135 patients, with an isolated, previously untreated, moderately differentiated to well-differentiated invasive squamous cell carcinoma of the pyriform sinus and a minimum of 3 years of follow-up, consecutively managed with a supracricoid hemilaryngopharyngectomy (SCHLP) at a single tertiary referral care center and locally controlled, the authors review in detail the surgical technique, highlight the potential technical pitfalls, and document the complications and long-term functional outcome. The overall postoperative mortality rate was 3.7%. The overall mortality rate directly related to the SCHLP was 1.5%. A significant surgical complication directly related to SCHLP completion was noted in 9.6% of cases. The mean lengths of time to removal of the tracheotomy and feeding tubes were 9 and 19 days, respectively. The mean duration of hospitalization was 25 days. Normal swallowing without aspiration by the first postoperative month was noted in 64.6% of patients. Temporary grade 1-2 aspiration and grade 3 aspiration were noted in 26.9% and 8.5% of patients, respectively. Overall, in our series, successful oral alimentation without gastrostomy or completion total laryngectomy was achieved in 91.9% of patients by the first postoperative year, and the incidences of permanent gastrostomy, completion total laryngectomy, and aspiration-related death were 0.7%, 1.5%, and 0.7%, respectively. A significant late complication related to the use of postoperative radiotherapy was noted in 26.5% of cases. From a functional point of view, such results suggest that SCHLP should be integrated among the various conservation treatment options available to patients with selected invasive squamous cell carcinoma of the pyriform sinus.

Supracricoid hemilaryngopharyngectomy in patients with invasive squamous cell carcinoma of the pyriform sinus. Part II: Incidence and consequences of local recurrence.

Supracricoid hemilaryngopharyngectomy (SCHLP) was performed in 147 patients over a 19-year period for previously untreated invasive squamous cell carcinoma of the pyriform sinus. With a minimum of 3 years' follow-up, the current retrospective series was designed to document the incidence, risk factors, and consequences of local recurrence following SCHLP. Before operation, 97.4% of patients had an induction chemotherapy regimen. A complete clinical response and a complete histologic regression were noted in 21.7% and 16.8% of patients, respectively. A significant statistical relationship (p = .0001) was noted between complete clinical response and complete histologic regression. Postoperative radiotherapy was used in 49.8% of patients. The overall local recurrence rate was 8.2%. The 5-year actuarial (Kaplan-Meier life-table method) local control estimate was 90.4%. As a function of T stage, the 5-year actuarial local control estimates were 96.2%, 91.1%, 92.9%, and 62.6% in patients with tumors classified as T1, T2, T3, and T4a, respectively. On univariate analysis, the overall local recurrence rate varied significantly, from 5.3% to 55.6% if the apex of the pyriform sinus was invaded (p = .02), 6.9% to 18.7% if the posterior pharyngeal wall was invaded (p = .03), and 6.3% to 60% if the margins of resection were positive (p = .02). In a stepwise regression model, positive margins of resection (odds ratio, 8.4; 95% confidence interval, 2.2 to 32.2; p = .002) and invasion of the apex of the pyriform sinus (odds ratio, 6.1; 95% confidence interval, 1.1 to 33.3; p = .04) were the variables statistically associated with an increased risk of local recurrence. Local recurrence resulted in a statistically significant increased risk of nodal recurrence (p = .005) and death (p < .004). The overall laryngeal preservation rate was 91.2%. From an oncological perspective, these results suggest that SCHLP should become a major tool in the armamentarium of the head and neck surgeon and should be integrated into future trials aimed at organ preservation in patients with invasive squamous cell carcinoma of the pyriform sinus.

Frontolateral vertical partial laryngectomy without tracheotomy for invasive squamous cell carcinoma of the true vocal cord: a 25-year experience.

On the basis of an inception cohort of 270 patients with a previously untreated invasive squamous cell carcinoma of the true vocal cord (232 T N0M0, 35 T2N0M0, and 3 T3N0M0) and a minimum of 3 years of follow-up, the authors analyze the oncological and functional outcomes following frontolateral vertical partial laryngectomy without tracheotomy. The 5-year Kaplan-Meier actuarial survival estimate ranged from 83.1% for T1 tumors to 67.2% for T2 tumors (p = .005). On univariate analysis, a significant statistical relationship was noted between reduced survival and the following variables: increased age, increased Charlson comorbidity index score over grade 0, increased tobacco intake, increased alcohol intake, increased T stage, local failure, nodal failure, and development of a metachronous second primary cancer. The hospital mortality rate was 0.4%. A significant postoperative surgical complication was noted in 49 patients (18.1%). The predominant significant surgical complication was wound infection (19 patients; 7%), followed by seroma and major subcutaneous emphysema. No significant statistical relationship was noted in a comparison of each, significant postoperative complication (including postoperative death) with the variables under analysis. The incidence of secondary tracheotomy was 0.4%. The incidence of completion laryngectomy due to functional problems was 0%. The 5-year Kaplan-Meier actuarial local control estimate was 91% for T1 tumors and 68.7% for T2 tumors (p <.0001). Within the T1 tumors, the 5-year Kaplan-Meier actuarial local control estimate ranged from 96.2% for tumors without anterior commissure involvement to 74.7% for tumors with anterior commissure involvement (p = .0002). On univariate analysis, a significant statistical relationship was noted between an increase in local recurrence and the following variables: increased T stage, anterior commissure involvement, and pathological margin involvement. The overall disease control rate and laryngeal preservation rate were 92.9% and 93.3%, respectively.

Metachronous second primary cancers after successful partial laryngectomy for invasive squamous cell carcinoma of the true vocal cord.

The current retrospective studies documented the incidence, sites of occurrence, risk factors, and outcome of metachronous second primary cancers (MSPCs) among an inception cohort of 410 patients with invasive squamous cell carcinoma of the true vocal cord successfully treated with partial laryngectomy at a single institution. The Kaplan-Meier actuarial life-table method was used to document the relationship between the incidence of MSPCs and survival data. Univariate analysis was performed for potential statistical relationships among the incidence of MSPCs, the site of occurrence, and different variables. The overall incidence of MSPCs was 23.9% (98/410). The 10-year actuarial survival estimate for MSPCs was 20.4%. The incidence curve of MSPCs was linear, resulting in a 2%/y rate of development for MSPCs. In univariate analysis, the only variable that demonstrated a statistical correlation with the incidence of MSPCs was smoking, with MSPCs being statistically more likely to occur in smokers than in nonsmokers (p = .04). The main sites of origin for MSPCs were the lung (25.5% of cases), other non-upper aerodigestive tract sites (32.7%), and the upper aerodigestive tract (41.8%). The 10-year actuarial estimates for MSPCs were 9.1% in the upper aerodigestive tract, 7.1% in sites other than the lung or upper aerodigestive tract, and 6.6% in the lung. The incidence curve for MSPCs was linear, whatever the site of origin, resulting in 1 %/y, 0.7%/y, and 0.6%/y rates of development for MSPCs in the upper aerodigestive tract, sites other than the lung or upper aerodigestive tract, and the lung, respectively. Survival was statistically reduced when an MSPC developed; the 10-year actuarial survival estimates were 76.8% in patients who did not develop an MSPC and 43.7% in patients who developed an MSPC (p < .0001). Overall, 68.4% of patients who developed an MSPC (67/98) died of this disease. The 10-year actuarial survival estimates were 24% for lung MSPCs, 43.7% for non-lung, non-upper aerodigestive tract MSPCs, and 63.4% for upper aerodigestive tract MSPCs.

Conventional transoral surgery for stage I-II squamous cell carcinoma of the tonsillar region.

BACKGROUND: The purpose of this study was to review the results of conventional transoral resection and neck dissection for stage I to II squamous carcinoma of the tonsillar region. METHODS: We conducted a retrospective review of 65 patients (stage I, 21 patients; stage II, 44 patients). Induction chemotherapy and postoperative radiation therapy (RT) were administered in 76.9% and 12.3%, respectively, of these cases. RESULTS: The postoperative course was uneventful in 96.9% of patients. Five-year actuarial estimates for local recurrence, nodal recurrence, distant metastasis, and survival were 0% to 7.6%, 0% to 7.8%, 0% to 7.3%, and 70.8% to 71.5% for patients with T1 to T2 carcinoma, respectively. Contralateral and retropharyngeal recurrence occurred in only 1 patient. CONCLUSION: Conventional transoral resection with ipsilateral neck dissection provides an alternative approach for patients with stage I to II squamous cell carcinoma (SCC) of the tonsillar region. A primary surgical approach spares the use of radiotherapy to eliminate late effects and to permit its use for subsequent management of metachronous head and neck second primary cancer.