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.

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.

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.

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.

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.

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.

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.

Lateral pharyngotomy for selected invasive squamous cell carcinoma of the lateral oropharynx--part I: how.

OBJECTIVES/HYPOTHESIS: To revisit the surgical technique of lateral pharyngotomy in patients with selected, isolated, and untreated invasive squamous cell carcinoma of the lateral oropharynx. To describe postoperative management, complications, and functional outcomes. STUDY DESIGN: Retrospective review from a French university teaching hospital. METHODS: Ninety-one patients consecutively underwent lateral pharyngotomy for selected T1­T4 squamous cell carcinoma of the lateral oropharynx. RESULTS: Of the patients, 73.6% and 98.9% experienced an uncomplicated surgical and medical postoperative course, respectively. There were no intraoperative deaths, but a single patient died in the immediate postoperative period from carotid rupture following salivary oropharyngeal fistula. The most common significant complications were severe postoperative swallowing impairment, pneumonia from aspiration, and salivary oropharyngeal fistula noted in 6.5%, 4.3%, and 4.3% of cases, respectively. In univariate analysis, none of the variables under analysis was related to the various significant complications noted and/or to immediate postoperative death. No patient had a permanent tracheotomy, whereas one had a permanent gastrostomy. Of the patients in whom a full course of radiation therapy was delivered postoperatively, 13.6% developed a major complication. CONCLUSIONS: From a functional point of view, lateral pharyngotomy is a safe, reliable surgery with few major complications and might be considered a valuable alternative to chemoradiation and/or mandibulotomy for selected tumors of the lateral oropharynx.

Lateral pharyngotomy for selected invasive squamous cell carcinoma of the lateral oropharynx. Part II: when and why.

OBJECTIVES/HYPOTHESIS: To analyze local failure following lateral pharyngotomy for selected untreated invasive squamous cell carcinoma (SCC) of the lateral oropharynx. STUDY DESIGN: Retrospective review from a university teaching hospital. METHODS: Inception cohort of 91 patients who underwent lateral pharyngotomy for an isolated and previously untreated selected invasive carcinoma of the lateral oropharynx classified as T1 (26), T2 (47), T3 (11), and T4 (7). Induction chemotherapy, neck dissection, and postoperative radiation therapy were used in 91.2%, 94.5%, and 53.5% of patients. RESULTS: The 5-year Kaplan-Meier estimate of local failure was 16.6% for T1, 19% for T2, 38.6% for T3, and 16.7% for T4 lesions (P = .46). In a logistic regression model, only positive margins of resection statistically increased (P = .01) the risk for local failure. In patients with safe margins of resection, the 5-year Kaplan-Meier estimate of local failure was 5.6% for T1 lesions, 10.7% for T2 lesions, 23.8% for T3 lesions, and 20% for T4 lesions (P = .4). Local failure had a significant impact on increased nodal failure (P = .001) and on reduced survival (P < .0001). CONCLUSION: The lateral pharyngotomy approach should be viewed as a valuable oncologic alternative to both mandibulotomy and chemoradiation in patients with selected SCC of the lateral oropharynx.

QTL mapping of growth-related traits in a full-sib family of rubber tree (Hevea brasiliensis) evaluated in a sub-tropical climate.

The rubber tree (Hevea spp.), cultivated in equatorial and tropical countries, is the primary plant used in natural rubber production. Due to genetic and physiological constraints, inbred lines of this species are not available. Therefore, alternative approaches are required for the characterization of this species, such as the genetic mapping of full-sib crosses derived from outbred parents. In the present study, an integrated genetic map was obtained for a full-sib cross family with simple sequence repeats (SSRs) and expressed sequence tag (EST-SSR) markers, which can display different segregation patterns. To study the genetic architecture of the traits related to growth in two different conditions (winter and summer), quantitative trait loci (QTL) mapping was also performed using the integrated map. Traits evaluated were height and girth growth, and the statistical model was based in an extension of composite interval mapping. The obtained molecular genetic map has 284 markers distributed among 23 linkage groups with a total length of 2688.8 cM. A total of 18 QTLs for growth traits during the summer and winter seasons were detected. A comparison between the different seasons was also conducted. For height, QTLs detected during the summer season were different from the ones detected during winter season. This type of difference was also observed for girth. Integrated maps are important for genetics studies in outbred species because they represent more accurately the polymorphisms observed in the genitors. QTL mapping revealed several interesting findings, such as a dominance effect and unique segregation patterns that each QTL could exhibit, which were independent of the flanking markers. The QTLs identified in this study, especially those related to phenotypic variation associated with winter could help studies of marker-assisted selection that are particularly important when the objective of a breeding program is to obtain phenotypes that are adapted to sub-optimal regions.

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.

Aspiration after supracricoid partial laryngectomy: Incidence, risk factors, management, and outcomes.

BACKGROUND: The aim of this study was to evaluate the incidence, risk factors, management, and outcome of postoperative aspiration in patients managed with a supracricoid partial laryngectomy (SCPL) for selected invasive squamous carcinoma of the larynx. METHODS: In all, 457 patients underwent SCPL at an academic, tertiary referral care center, 1975-2000. The incidence of aspiration defined in accord with Pearson's scale was recorded. Univariate and multivariate analyses were performed for potential statistical relation with various variables. The management and outcome of aspiration are presented. RESULTS: Normal swallowing without aspiration was noted in 259 patients (58.9%). Grades 1, 2, and 3 aspiration occurred in 87, 48, and 53 patients (19%, 10.5%, and 11.6%), respectively. A significant relationship was noted between aspiration and increased age, performing cricohyoidopexy, not repositioning the pyriform sinuses, and resecting an arytenoid cartilage. A prediction model, based on multinomial logistic regression, found that the probability that severe aspiration cases (grade 2-3) exceeded the subclinical ones (grade 0-1) occurred only when a cricohyoidopexy with partial or total arytenoid resection was performed in patients >70 years of age (p = .0000001). Management of aspiration required a temporary gastrostomy, a permanent gastrostomy, and a completion total laryngectomy in 65, 3, and 7 of 188 patients (34.5%, 1.6%, and 3.7%, respectively) who aspirated, and 65, 3, and 7 of 457 of the entire population (14.2%, 0.6%, and 1.5%, respectively). Aspiration-related death was not encountered in the current series. CONCLUSIONS: Aspiration after SCPL is a common but rarely severe event, with a low incidence for permanent gastrostomy or completion laryngectomy. Aspiration can be minimized with careful patient selection and precise surgical technique.

[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.

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.

Horizontal supraglottic partial laryngectomy for selected squamous carcinoma of the vallecula.

BACKGROUND: Our aim was to determine the incidence of local control in patients with selected squamous carcinoma of the vallecula treated with horizontal supraglottic laryngectomy; to analyze the consequences of local recurrence in terms of nodal recurrence, distant metastasis, survival, causes of death, overall local control, and laryngeal preservation; and to identify any clinical factors predictive of these outcomes. METHODS: This was a retrospective nonrandomized case series in a university teaching hospital. An inception cohort of 95 previously untreated patients were followed until death or for a minimum of 5 years. According to the 2002 Union Internationale Contre le Cancer (UICC) staging classification system, the tumor was classified as T1, T2, and T3 in 13, 60, and 22 patients, respectively, while disease in 67 patients was considered to be in stages III to IV. All patients underwent a horizontal partial supraglottic partial laryngectomy. Ninety-four patients had an associated neck dissection. An induction chemotherapy regimen was used in 91 patients; postoperative radiation therapy was given for 49 patients. The main outcome measures were local recurrence, nodal recurrence, distant metastasis, and survival. RESULTS: The 1-, 3-, and the 5-year actuarial survival estimates were 86.3%, 64.2%, and 47.4%, respectively. Overall, the main causes of death were as follows: metachronous second primary tumor (47.2% of patients), intercurrent disease (16.7%), distant metastasis (15.3%), local recurrence (6.3%), and nodal recurrence, (4.2%). The 1-, 3-, and 5-year actuarial local recurrence rates were 4.5%, 11%, and 11%, respectively. Nine patients developed a local recurrence; 3 were successfully salvaged. Using multivariate analysis, no single variable was found to increase the risk for local recurrence. The overall laryngeal preservation rate and local control rate were 89.5% (85/95) and 93.4% (89/95), respectively. Local recurrence was associated with a significant increase in nodal recurrence (p <.04) and distant metastasis (p = .03). CONCLUSIONS: Based on this experience, horizontal partial supraglottic laryngectomy appears to be a valid approach for functional organ-preservation in patients with selected T1-T3 SCC of the vallecula.

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.

Resection of selected invasive squamous cell carcinoma of the pyriform sinus by means of the lateral pharyngotomy approach: the partial lateral pharyngectomy.

BACKGROUND: Although the lateral pharyngotomy is a well-known surgical procedure, to our knowledge, no published reports have described the results achieved with a lateral pharyngectomy approach in patients with isolated and previously untreated selected invasive squamous cell carcinoma of the lateral wall of the pyriform sinus. METHODS: The medical files and operative charts of 30 patients with an isolated, and previously untreated, squamous cell carcinoma of the pyriform sinus, treated for cure by lateral partial pharyngectomy and primary closure, as well as postoperative radiotherapy (n = 22), and preoperative chemotherapy (n = 8), were retrospectively studied. Sixteen tumors were classified as T1 and 14 as T2. All patients but one were followed until death. RESULTS: Three patients (9%) died in the immediate postoperative period (two from medical complications and one from a surgery-related complication). Overall, 29 patients died, resulting in a 77.7%, 40%, 23.3%, and 15% 1-, 3-, 5- and 10-year Kaplan-Meier actuarial survival estimate, respectively. Only one patient had a serious postoperative complication develop. All patients were decannulated. No patients required a gastrostomy and/or completion total laryngectomy for functional reasons. Local recurrence occurred in four patients (13%). The 3-and 5-year Kaplan-Meier actuarial local control estimates were 88.5% and 79.6%, respectively. The use of a platin-based induction chemotherapy (p = .05) regimen was the only variable that was significantly statistically related to local recurrence. Overall, a 93.3% laryngeal preservation rate was achieved. CONCLUSION: Partial pharyngectomy by means of the lateral pharyngotomy combined with postoperative radiation therapy is an efficient and function-sparing approach to control selected invasive squamous cell carcinomas of the lateral wall of the pyriform sinus.

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.