Dequanter D, Lothaire P, Zouaoui K, Brohée D
Epidemiology and clinical characteristics of larynx and hypopharynx carcinoma: a comparative study in the Hainaut and review of the literature.
Acta Chir Belg. 2012 Nov-Dec; 112(6):423-5 [PubMed]

INTRODUCTION: The epidemiology and clinical picture of laryngeal and hypopharyngeal carcinomas have changed significantly in the past 50 years. The aim of this study was to analyze selected epidemiological and clinical characteristics of laryngeal and hypopharyngeal carcinoma.
METHODS: A complete chart review of all patients records was conducted. All the patients who were diagnosed as having laryngeal or hypopharyngeal cancer from January 1, 2004 through December 31, 2009 were included in the study. The demographics of the patient population, the disease profile were analyzed.
RESULTS: 138 patients with laryngeal or hypopharyngeal disease were treated. 76 patients presented a laryngeal cancer. Disease characteristics indicated that most cases of supraglottic cancer were in a locally advanced stage (84.4%), whereas most patients with glottis cancer were diagnosed with early stage (63.3%). A hypopharyngeal cancer was diagnosed in 62 cases. A significant increasing trend in hypopharyngeal cancer has been seen in males. The majority of the patients was alcohol consumers and had a histology showing squamous cell carcinoma. There were 33 females and 105 males whose ages ranged at presentation from 47 to 86 years. Of the 138 patients treated, 24 and 47 patients were respectively T3 and T4 and 37 patients were N1, 37 patients N2 and 10 patients N3 (Table I). Most patients had stage IV disease (65/138). Majority of cases presented with local advanced stage. Of the 138 patients treated, 24 and 47 patients were respectively T3 and T4. The highest rate of local advanced stage was observed in patients with pyriform sinus carcinomas (81%); the lowest rate was observed for glottis tumors (41.8%). Regional lymph node metastases were diagnosed in 61% of the analyzed cases. 37 patients were N1, 37 patients N2 and 10 patients N3. The highest rate (82.2%) of regional lymph node metastases were observed in cases of pyriform sinus carcinomas, and the lowest (31.7%) in glottis carcinomas. Most patients had stage IV disease (65/138). 49 patients received radiotherapy; 48 patients were treated by surgery followed by (chemo)radiotherapy. 41 patients were treated initially by concomitant chemoradiotherapy.
CONCLUSION: A tendency for increasingly younger patients to develop larynx and hypopharynx carcinomas was observed. Most patients had stage IV disease but no trend for a percentage increase in locally advanced tumors was observed. A significant increasing trend in hypopharyngeal cancer has been seen in males.

Kotromanović Z, Mihalj H, Zubcić Z, et al.
Angiosarcoma of the hypopharynx: case report.
Coll Antropol. 2012; 36 Suppl 2:185-7 [PubMed]

Angiosarcomas are malignant neoplasias of rapid growth that emerge from endothelial cells. They are rarely found in the area of the head and neck and account less than 0.1% of all head and neck malignancies. In some cases it has been linked to trauma, radiation and angiectasia but the etiology mainly remains unknown. Here we report a case of angiosarcoma of pyriform sinus manifested by dysphagia and dysphonia. The patient underwent endoscopic hypopharyngeal excision followed by radiation therapy with a good result. Our patient remains tumor free after two years. The purpose of this article is to add another case of primary angiosarcoma of a rare site, the hypopharynx.

Chen AY, Hudgins PA
Pitfalls in the staging squamous cell carcinoma of the hypopharynx.
Neuroimaging Clin N Am. 2013; 23(1):67-79 [PubMed]

To accurately interpret pretreatment and posttreatment imaging in patients with hypopharyngeal squamous cell carcinoma (SCC), one must understand the complex anatomy of this part of the aerodigestive system. Common patterns of spread must be recognized, andpitfalls in imaging must be understood. This article reviews the epidemiology, anatomy, staging, treatment, and pitfalls in imaging of hypopharyngeal SCC.

Ortiz M, Giraldez LA, Riera-March A
Synovial sarcoma of the hypopharynx in pregnancy.
Bol Asoc Med P R. 2012 Jul-Sep; 104(3):55-6 [PubMed]

Synovial sarcomas of the hypopharynx are a rare form of soft tissue sarcomas. In the head and neck, they are most commonly found on the pharyngeal wall in areas that do not have synovial cells. We review a case of a 23 year-old pregnant female who presented to our hospital with acute airway obstruction due to a large hypopharynx lesion. She underwent emergency tracheotomy and tumor debulking. Pathology revealed synovial sarcoma. After the procedure the patient went into labor delivering a 29 weeks premature child. Six weeks after being discharged from the hospital the patient had a partial pharyngectomy performed to excise the remnant base of the tumor. She has had no recurrence at the 30-month post-operative period.

Liu W, McDaniel J, Li X, et al.
Brachytherapy using injectable seeds that are self-assembled from genetically encoded polypeptides in situ.
Cancer Res. 2012; 72(22):5956-65 [PubMed] Article available free on PMC after 15/11/2013

Brachytherapy is a common clinical technique involving implantation of sealed radioactive "seeds" within a tumor to selectively irradiate the tumor mass while minimizing systemic toxicity. To mitigate the disadvantages associated with complex surgical implantation and subsequent device removal procedures, we have developed an alternative approach using a genetically encoded peptide polymer solution composed of a thermally responsive elastin-like polypeptide (ELP) radiolabeled with (131)I that self-assembles into radionuclide seeds upon intratumoral injection. The formation of these nontoxic and biodegradable polymer seeds led to prolonged intratumoral retention (~85% ID/tumor 7 days postinjection) of the radionuclide, elicited a tumor growth delay in 100% of the tumors in two human xenografts (FaDu and PC-3), and cured more than 67% of tumor-bearing animals after a single administration of labeled ELP. These results suggest that in situ self-assembly of biodegradable and injectable radionuclide-containing polypeptide seeds could be a promising therapeutic alternative to conventional brachytherapy.

Chan JY, Liu LH, Wei WI
Early prediction of anastomotic leakage after free jejunal flap reconstruction of circumferential pharyngeal defects.
J Plast Reconstr Aesthet Surg. 2013; 66(3):376-81 [PubMed]

BACKGROUND: Anastomotic leakage from the free jejunal flap, if diagnosed late, can result in catastrophes. Our study aims to look for clinical parameters that allow early identification of leakage so that appropriate interventions can be taken.
METHOD: Between 1980 and 2011, consecutive patients with free jejunal flap reconstruction of circumferential pharyngeal defects were included. A retrospective chart review was then performed comparing the clinical parameters (body temperature, heart rate, serum albumin, haemoglobin and white cell count) between patients with no leakage and those with clinical and radiological leakage.
LEVEL OF EVIDENCE: 4.
RESULTS: Ninety-six patients were included in the study. The median age was 62 years. Majority (69.8%) of the defects were created after resection of tumours in the hypopharynx. Five (5.2%) patients had clinical leakage and 12 (12.5%) had radiological leakage. There was no significant difference in body temperature, heart rate, incidence of atrial fibrillation and haemoglobin level between those with and without leakage. The serum white cell count was higher in the patients who leaked, but it became statistically significant only after day 7 postoperatively. The serum albumin level was significantly lower in patients with anastomotic leakage starting as early as day 3 after surgery, and the difference persisted until the leak was controlled. However, there was no significant difference in the plasma albumin level between those with clinical or radiological leak.
CONCLUSION: Both serum albumin level and white cell count identified the presence of anastomotic leakage from the free jejunal flap. Serum albumin allows early prediction of leakage so that early interventions can be taken to avoid the damage resulting from the delay in diagnosis.

Poovaneswaran S, Paleri V, Charlton F, et al.
Cutaneous metastases from head and neck squamous cell carcinoma.
Med J Malaysia. 2012; 67(4):430-2 [PubMed]

The presence of cutaneous metastases in squamous cell carcinomas of the head and neck (SCCHN) is rare and associated with a dismal prognosis. It is vital to distinguish these lesions from direct invasion of the skin by SCCHN or primary cutaneous malignancies as the prognosis is vastly different and so is the management. In this case report, we present four cases of cutaneous metastases and also briefly review the literature pertaining to this phenomenon.

Kuo YL, Chang CF, Chang SY, Chu PY
Partial laryngopharyngectomy in the treatment of squamous cell carcinoma of hypopharynx: analysis of the oncologic results and laryngeal preservation rate.
Acta Otolaryngol. 2012; 132(12):1342-6 [PubMed]

CONCLUSION: Partial laryngopharyngectomy (PLP) provides acceptable oncologic results and laryngeal preservation rate in selected patients with squamous cell carcinoma of the hypopharynx. Even when local recurrence develops, the chance of successful salvage is still high.
OBJECTIVES: To evaluate the oncologic results and laryngeal preservation rate in patients with squamous cell carcinoma of the hypopharynx who underwent PLP.
METHODS: The results of 39 patients who underwent PLP were compared with those of 91 patients who underwent total laryngectomy (TL).
RESULTS: The distribution of the primary T stages were 23 (59%) pT2, 9 (23%) pT3, and 7 (18%) pT4; the pathologic stages were 8 patients (21%) stage II, 9 (23%) stage III, and 22 (56%) stage IV. All of the patients also had ipsilateral or bilateral neck dissections. Eighteen patients (46%) received postoperative adjuvant therapy. After a median follow-up of 39 months, 17 patients (44%) had recurrence, including 12 local, 2 regional, and 3 distant lesions. The 5-year overall and disease-specific survival were 44% and 56%, respectively; functional preservation was 62%. The recurrence rate was similar in patients treated with PLP and TL (44% vs 36%, p = 0.431); the local recurrence rate was higher after PLP than after TL (31% vs 8%, p = 0.001). The salvage surgery was successful in four of the six patients (67%). After salvage treatment, the 5-year overall survival (44% vs 47%) and disease-specific survival (56% vs 62%) were similar in the two groups.

Lee JC, Hsu WT, Yang CC, Chang SH
A fabricated forearm free flap with accompanying phonation tube for simultaneous reconstruction of a pharyngolaryngeal circumferential defect and voice loss: new surgical modification with functional phonation outcome.
Laryngoscope. 2013; 123(2):344-9 [PubMed]

BACKGROUND: Total pharyngolaryngectomy is potentially ablative surgery, resulting in compromise of some most basic functions of life, including speech and swallowing. Tracheoesophageal puncture is the gold standard for voice restoration. But it still has prosthesis-related problems.
OBJECTIVES/HYPOTHESIS: We designed a uniquely customized radial forearm free flap (RFFF), which also incorporated a region for phonation tube (PT) creation, for the dual purpose of circumferential laryngopharyngeal defect reconstruction and voice production.
METHODS: From August 2005 to September 2010, there were 18 male patients with late-stage hypopharyngeal cancer (HPC) or laryngeal cancer (LC) who received one-stage reconstruction with the fabricated RFFF-accompanying PT after total pharyngolaryngectomy. We recorded the phonation outcome of phonation efficacy (PE) and maximal phonation time (MPT) postoperatively within 1 month and at least 1 year after surgery.
RESULTS: Nine patients suffered from HPC and the others suffered from LC. Twelve patients received concurrent chemoradiotherapy after surgery. The follow-up time was 12 to 56 months (mean 28.7 months). There was no significant variance in the PE (79.72%, SD=21.93% vs. 62.50%, SD=39.60%, respectively; p = 0.115) and MPT (2.58 seconds, SD=1.80 vs. 2.97 seconds, SD=3.96, respectively; p = 0.878) between the first and last follow-up points, even when the patients were grouped by radiotherapy status after surgery or by disease group.
CONCLUSIONS: The phonation outcome in our experience was satisfactory and it tolerated postoperative radiotherapy during at least the 12-month follow-up period.

Perez-Smith D, Wagels M, Theile DR
Jejunal free flap reconstruction of the pharyngolaryngectomy defect: 368 consecutive cases.
J Plast Reconstr Aesthet Surg. 2013; 66(1):9-15 [PubMed]

BACKGROUND: The Jejunal Free Flap (JFF) was first described by Seidenberg in 1957 for the reconstruction of pharyngolryngectomy defects. Historically, its outcome profile has been better than alternative reconstructions. Recently, the use of tubed Fasciocutaneous Free Flaps (FCFF) has been increasing as series reporting outcomes superior or equivalent to JFF are published. Our experience with JFF has been more positive than recently published reports suggest. This study aims to provide an accurate and up-to-date assessment of outcomes in JFF reconstruction of pharyngolaryngectomy defects and to compare these results to those of contemporary alternative techniques.
METHODS: 368 Consecutive free jejunum reconstructions were performed for pharyngolaryngectomy defects between 1977 and 2010. All patients had been assessed by a multidisciplinary Head and Neck Clinic prior to surgery. A systematic review of recent literature pertaining to pharyngolaryngectomy reconstruction outcomes was undertaken for comparison with our dataset.
RESULTS: 70.9% of tumours in this series were T-grade 3 or 4. Perioperative mortality was 3.8% and flap failure occurred in 2.98%. The incidence of anastomotic leak was 8.2% and stricture occurred in 10.9%. A full oral diet was maintained by 91.6% of patients by day 12 on average. 70.6% underwent primary tracheo-oesophageal puncture and of these 78.1% had effective speech.
CONCLUSIONS: Overall, our data compares favourably with other series. The strengths of the JFF reconstruction are the capacity to maintain an oral diet, low stricture and leak rates and the versatility to reconstruct long segment defects. We have observed variability in leak rates throughout the study period, which may be operator dependant. The gap between outcomes for FCFF and JFF reconstructions has narrowed but the latter remains our reconstruction of choice for pharyngolaryngectomy defects.

Peng H, Wang SJ, Yang X, et al.
Infrahyoid myocutaneous flap for medium-sized head and neck defects: surgical outcome and technique modification.
Otolaryngol Head Neck Surg. 2013; 148(1):47-53 [PubMed]

OBJECTIVES: To evaluate the surgical outcomes associated with infrahyoid myocutaneous flaps used in the reconstruction of medium-sized defects following head and neck cancer resection, as well as to discuss a novel technique modification.
STUDY DESIGN: Case series with chart review.
SETTING: University cancer hospital.
SUBJECTS AND METHODS: A total of 20 patients with oral or hypopharyngeal carcinoma who underwent infrahyoid myocutaneous flap reconstruction between June 2005 and December 2011 were retrospectively studied. A novel technical modification of flap harvest, preservation of the cranial portion of the anterior jugular vein, was attempted in 15 flaps and was successful in 13 flaps. Functional evaluation was performed in all patients 3 to 6 months after the operation or postoperative radiation.
RESULTS: Total flap necrosis, marginal skin paddle necrosis, and total skin paddle loss were observed in 1, 2, and 1 patient(s), respectively. Pharyngocutaneous fistula without flap problem occurred in 1 patient. No flap complications occurred in 13 cases where the cranial portion of the anterior jugular vein was successfully preserved. Functional results were excellent in 16 patients, good in 3 patients, and fair in 1 patient.
CONCLUSION: The infrahyoid myocutaneous flap is a reliable and convenient technique that can serve as an alternative to free flaps in the reconstruction of medium-sized defects of the oral cavity or hypopharynx. Preservation of the cranial portion of the anterior jugular vein is a novel technical modification of harvesting this flap, which may result in better venous return of the skin paddle and reduce skin paddle necrosis.

Kuno H, Onaya H, Iwata R, et al.
Evaluation of cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinoma with dual-energy CT.
Radiology. 2012; 265(2):488-96 [PubMed]

PURPOSE: To evaluate the clinical usefulness of dual-energy computed tomography (CT) with weighted-average (WA) images and iodine overlay (IO) images in the evaluation of laryngeal cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinoma (SCC).
MATERIALS AND METHODS: The institutional review board approved this retrospective study, and written comprehensive consent was obtained from all patients. Seventy-two consecutive patients underwent 128-section dual-source dual-energy CT to stage laryngeal (n=27) or hypopharyngeal (n=45) cancer. Three observers who were blinded to the patients' clinical histories and histopathologic findings evaluated cartilage invasion on WA images alone or in combination with IO images (nonossified cartilages were selectively evaluated on IO images) by using a five-point scale. Thirty of the 72 patients (42%) underwent surgery, and findings from histopathologic examination in those patients were used as the standard of reference for the evaluation of diagnostic performance with receiver operating characteristic (ROC) curve analysis and in terms of sensitivity and specificity. Interobserver reproducibility was calculated with κ statistics.
RESULTS: For thyroid cartilage, the area under the ROC curve (AUC) of the WA plus IO images was marginally larger than that for WA images alone (AUC=0.957 vs 0.870, respectively; P=.075). The specificity of WA plus IO images was significantly superior to that of WA images alone (96% vs 70%, respectively; P=.031), with no compromise to the sensitivity (86% for both). For thyroid and cricoid cartilages, the interobserver reproducibility was higher for diagnoses made with WA plus IO images (κ=0.68-0.72 and 0.64-0.79, respectively) than for those made with WA images alone (κ=0.29-0.56 and 0.20-0.64, respectively).
CONCLUSION: Combined analysis of WA and IO images obtained with dual-energy CT improves the diagnostic performance and interobserver reproducibility of evaluations of laryngeal cartilage invasion by SCC.

Tulunay-Ugur OE, McClinton C, Young Z, et al.
Functional outcomes of chemoradiation in patients with head and neck cancer.
Otolaryngol Head Neck Surg. 2013; 148(1):64-8 [PubMed]

OBJECTIVE: Concurrent chemoradiotherapy (CCRT) has become the treatment of choice for oropharyngeal and hypopharyngolaryngeal cancers in many centers. Although it has increased the rates of organ preservation, there has also been an increase in treatment-related complications. We aimed to evaluate the functional outcomes of CCRT in head and neck cancer.
STUDY DESIGN: Case series with chart review.
SETTING: Tertiary cancer center.
SUBJECTS AND METHODS: A retrospective study of patients treated with CCRT at the University of Arkansas for Medical Sciences was performed. Demographic data and treatment outcomes were extracted, specifically feeding tube and tracheotomy dependence and number of esophageal dilatations.
RESULTS: Of the 243 patients treated with concurrent chemoradiotherapy (5-fluorouracil + cysplatin and radiotherapy), 152 patients received a feeding tube. The median percutaneous gastrostomy tube (PEG) use was 9 months (range, 1-96 months). More than 70% of the patients who had a PEG more than 6 months had a T3 or T4 tumor. Thirty-seven patients underwent esophageal dilatations, (median, 1; range, 1-7). The median use of a tracheotomy was 7 months, and 77% of these patients were treated for hypopharyngolaryngeal cancer.
CONCLUSIONS: Despite major improvement in locoregional control rates, CCRT has a significant negative impact on the functional outcomes of head and neck cancer patients, with a high number of patients remaining PEG and tracheotomy dependent.

Filipovska-Mušanović M, Hodžić D, Hrnčić N, Hatibović H
Quality of life in patients with larygeal/hypopharyngeal cancer following total/partial laryngectomy.
Med Glas (Zenica). 2012; 9(2):287-92 [PubMed]

AIM: To estimate the quality of life (QOL) of patients with carcinoma of larynx/hypopharynx using the EORTC QLQ-C30 and QLQ-H and N35 questionnaires in relation to the reference values (RV), total (TL) / partial (PL) laryngectomy/ pharyngectomy, combined treatment (surgery, radiotherapy, chemotherapy) (CT) and the time elapsed since surgery.
METHODS: The questionnaires were answered by 45 patients in the first 6 months of 2011. Sixteen (35.6%) patients had PL and 29 (64.4%) TL. Postoperatively, CT was performed in 34 (75.6%) patients (group A), and 11 (24.4%) patients (group B) only had surgery. The time elapsed from surgery of ≤12 months was found in 11 (24.4%) patients in the group A1, and 34 (75.6%) of more than 12 months in the group B1. Comparison was made between all scales of the questionnaires, global (GS), functional (FS) and general symptomatic (GSS) QLQ-C30 and specific symptomatic scale (SSS) QLQ-H and N35.
RESULTS: Comparing our results from all scales of both questionnaires with RV there was no statistically significant differences, except for SSS relating to speech problems (p=0.052574). Comparing PL and TL there was a decrease in FS (p=0.025517) and increased problems with speech, swallowing, sensation, coughing and social contact in SSS (p=0.017595) in TL. Comparing A and B groups, there was a decrease in FS (p=0.00531) increase of all symptoms in GSS (p=0.043388) and SSS (p=0.0505385) in the A group. Comparing A1 and B1 groups better FS (p=0.042271) was registered in A1.
CONCLUSION: Quality of life of our patients is not significantly different from the QOL of similar patients in the world. Comparing all groups, QLQ-C30 and QLQ-H and N35 showed us clear differences in QOL and their clinical use is justified.

Al-Mamgani A, Mehilal R, van Rooij PH, et al.
Toxicity, quality of life, and functional outcomes of 176 hypopharyngeal cancer patients treated by (chemo)radiation: the impact of treatment modality and radiation technique.
Laryngoscope. 2012; 122(8):1789-95 [PubMed]

OBJECTIVES/HYPOTHESIS: The main goal of the current study was to comprehensively address the impact of chemoradiation and radiation techniques on toxicity, quality of life (QoL), and functional outcome.
STUDY DESIGN: Retrospective analysis of toxicity and functional outcome and prospective QoL assessment.
METHODS: From 1996 to 2010, 176 consecutive patients with hypopharyngeal cancer (HPC) were treated with (chemo)radiotherapy. End points were acute and late toxicity, QoL assessment, and functional outcome using laryngoesophageal dysfunction-free survival (LED-FS) defined by the Laryngeal Preservation Consensus Panel.
RESULTS: Chemoradiation significantly increased grade 3 acute toxicity compared to radiotherapy alone (71% vs. 55%, P = .02). The 3-year grade ≥2 late toxicity was 32%. Intensity-modulated radiotherapy (IMRT) significantly reduced late toxicity compared to three-dimensional conformal radiotherapy (3DCRT) (24% vs. 44%, P = .007). Slight deterioration in QoL scores was observed on almost all scales, and was more pronounced in patients treated with chemoradiation, albeit not statistically significant except for xerostomia. Chemoradiation, compared to radiotherapy alone, improved LED-FS at 3 years (51% vs. 24% for the entire group and 83% vs. 63% for the 78 living patients at last follow-up, respectively [P = .05]).
CONCLUSIONS: Compared to radiotherapy alone, chemoradiation significantly improved functional outcome, increased acute toxicity, but without significant increase in late radiation-induced side effects. Statistically significant deterioration in QoL scores was reported only for xerostomia. IMRT, compared to 3DCRT, reduced the incidence and severity of acute and late toxicity, thereby broadening the therapeutic window, and may allow dose escalation for further improvement of outcomes of laryngeal preservation protocols.

Cheng HT, Ma H, Tsai CH, et al.
A three-dimensional stereoscopic monitor system in microscopic vascular anastomosis.
Microsurgery. 2012; 32(7):571-4 [PubMed]

Microvascular procedures not only demand precise movements but also usually require a long operation time. Using a conventional surgical microscope, microvascular surgeons need to keep the neck in a fixed flexion posture, which can lead to physical fatigue. Thus, our aim was to develop a three-dimensional (3D) monitoring system to improve the microsurgery environment. It consists of four main parts: the surgical microscope, the charge-coupled devices, the 3D multiplexer, and the 3D monitor. Two patients with head and neck cancers who underwent tumor resections were reconstructed with free flap microsurgeries. Both artery anastomoses were completed successfully and the postoperative courses of the two patients were smooth. Vascular anastomosis can be performed successfully with the help of the new 3D display system. Although the artery anastomosis procedures took longer than under a surgical microscope, the 3D system offers another option to improve the working environment for surgeons.

Harada R, Isobe K, Watanabe M, et al.
The incidence and significance of retropharyngeal lymph node metastases in hypopharyngeal cancer.
Jpn J Clin Oncol. 2012; 42(9):794-9 [PubMed]

OBJECTIVE: To evaluate the incidence and clinical significance of retropharyngeal lymph node metastasis in hypopharyngeal cancer.
METHODS: Pretreatment computed tomography and/or magnetic resonance images of 152 patients treated between 1998 and 2009 were retrospectively reviewed. The prognostic significance of retropharyngeal lymph node metastasis for 116 patients who received definitive treatment was also analyzed.
RESULTS: Twelve patients (8%) were radiologically positive for retropharyngeal lymph node metastasis. Tumors originating from the posterior wall showed significantly higher incidence of retropharyngeal lymph node than those originating from other sites (23.8 vs. 5.3%, P = 0.01). The majority of patients with retropharyngeal lymph node involvement experienced distant metastasis. The overall survival rate of patients with retropharyngeal lymph node metastasis was worse than in those lacking retropharyngeal lymph node involvement (0 vs. 68.8% at 2 years, P < 0.01), and so was the cause-specific survival rate (0 vs. 74% at 2 years, P < 0.01).
CONCLUSIONS: Patients with hypopharyngeal cancer, especially those with posterior wall tumors, are at high risk for retropharyngeal lymph node involvement. Patients with retropharyngeal lymph node metastasis developed distant metastasis frequently, and showed dismal outcomes.

Mura F, Bertino G, Occhini A, et al.
Advanced carcinoma of the hypopharynx: functional results after circumferential pharyngolaryngectomy with flap reconstruction.
Acta Otorhinolaryngol Ital. 2012; 32(3):154-7 [PubMed] Article available free on PMC after 15/11/2013

Surgical treatment of advanced cancers of the hypopharynx inevitably impairs swallowing, respiration and phonation. The purpose of this study was to analyze the functional results after circumferential pharyngolaryngectomy (CPL) and flap reconstruction, in order to offer decisional guidelines for the choice of the most effective reconstructive method. We performed a retrospective analysis on the medical records of patients submitted to reconstructive surgery after CPL from July 1991 to November 2011. 75% of the 94 patients underwent reconstruction with a free flap (group A), while 25% underwent reconstruction with a pedicled flap (group B); 80% of patients in group A and none in group B were discharged with a free diet; 14% of patients in group A and 26% in group B were unable to resume oral feeding and were discharged with NG-tube or PEG. None of the patients acquired a satisfactory oesophageal voice; 17% of patients in group A and 7% in group B underwent voice restoration with tracheo-oesophageal voice-prosthesis. In conclusion, free flaps should be considered the first choice for reconstruction of the hypopharynx after CPL because of the better functional results obtained. Pedicled flaps represent a valid alternative in patients with contraindications to microvascular surgery.

Montemari G, Rocco A, Galla S, et al.
Hypopharynx reconstruction with pectoralis major myofascial flap: our experience in 45 cases.
Acta Otorhinolaryngol Ital. 2012; 32(2):93-7 [PubMed] Article available free on PMC after 15/11/2013

A pectoralis major myofascial flap (PMMF) is a simple variant of the pectoralis major myocutaneous flap (PMMC), and allows avoiding some of the disadvantages of Ariyan's technique while reducing well-known, overall complications. This is a retrospective analysis of 45 hypopharyngeal reconstructions (40 immediate reconstructions after subtotal pharyngolaryngectomy and 5 performed during revision surgery) using PMMF flap, performed from February 1995 to February 2008 in the Department of Otolaryngology at the "San Camillo- Forlanini" Hospitals in Rome, in collaboration with the Department of Plastic Surgery. In our series, we observed postoperative flap-related complications in 6.7% of cases. The incidence of major flap complications requiring surgical revision was 2.2%. Two minor complications were seen: hypopharyngeal stenosis and a salivary fistula, both of which were managed without surgery. Total or partial necrosis did not occur in any case. There were four postoperative deaths, but which were not related to flap complications in any case. In the remaining cases, oesophageal X-ray imaging showed the absence of fistulas and adequate calibre of the reconstructed tract; oral intake started within postoperative day 10-12, without swallowing problems of liquid or solid food. Postoperative radiotherapy performed in 30 patients was well tolerated. The PMMF flap is safe one-step procedure with low morbidity that is particularly useful for partial hypopharyngeal reconstructions, overcoming the disadvantages of the PMMC flap and offering comparable results to fasciocutaneous free flaps.

Weinstein GS, O'Malley BW, Magnuson JS, et al.
Transoral robotic surgery: a multicenter study to assess feasibility, safety, and surgical margins.
Laryngoscope. 2012; 122(8):1701-7 [PubMed]

OBJECTIVES/HYPOTHESIS: Our objective was to determine the safety, feasibility, and the adequacy of surgical margins for transoral robotic surgery (TORS), by reviewing the early results from independent institutional review board-approved clinical trials in three separate institutions.
STUDY DESIGN: Pooled Data from Independent Prospective Clinical Trials.
METHODS: One hundred ninety-two patients were initially screened, but inadequate exposure did not permit TORS in 13 (6.7%). For two additional patients, TORS was begun but intraoperatively converted to an open procedure. Thus, the intent-to-treat population was 177 patients (average age, 59 years; 81% male), predominantly comprised of tumors arising in the oropharynx (139, 78%) and larynx (26, 15%). TORS was performed for 161 (91%) patients with malignant disease: 153 (95%) with squamous cell carcinoma (T1 [50, 32.7%], T2 [74, 48.4%], T3 [21, 13.7%], T4 [8, 5.2%]), six patients (3.72%) with salivary gland tumors, and two patients with carcinoma in situ. The average follow-up was 345 days.
RESULTS: There was no intraoperative mortality or death in the immediate postoperative period. Average estimated blood loss was 83 mL; no patient required transfusion. The rate of positive margins was 4.3%. Twenty-nine patients (16%) experienced 34 serious adverse events that required hospitalization or intervention (grade 3) or were considered life threatening (grade 4, 2.3%). Tracheostomy was performed in 12.4% of all patients (22/177), but only 2.3% had a tracheostomy at last follow-up. For all patients undergoing TORS without previous therapy, the percutaneous endoscopic gastrostomy dependency rate was 5.0%. The average hospital stay was 4.2 days.
CONCLUSIONS: Based on this multicenter study, TORS appears to be safe, feasible, and as such play an important role in the multidisciplinary management of head and neck cancer.

Krstevska V, Stojkovski I, Zafirova-Ivanovska B, Crvenkova S
Prognostic factors in patients with advanced hypopharyngeal squamous cell carcinoma treated with concurrent chemoradiotherapy.
J BUON. 2012 Apr-Jun; 17(2):327-36 [PubMed]

PURPOSE: The aim of this study was to evaluate different prognostic factors affecting response to treatment, locoregional control (LRC) and survival in patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC).
METHODS: A retrospective analysis of 41 patients with advanced HPSCC who had undergone definitive concurrent chemoradiation treatment between January 2006 and October 2009 was performed.
RESULTS: Complete composite response (CCR) was achieved in 27 patients (65.9)). Significant prognostic factors for CCR were T stage, technique of radiation, and gross tumor volume (GTV). Unfavorable prognostic factors for CCR in multivariate analysis were higher T stage and radiation technique with electron-photon fields. The 2-year LRC rate was 51.3%. The 2-year disease-free survival (DFS) and overall survival (OS) rates were 29.3% and 32.8%, respectively. Significant prognostic factors for LRC, DFS, and OS in univariate analysis were T stage, overall stage, and GTV. OS was also significantly influenced by N stage. In multivariate analysis T stage was found to be the only significant independent prognostic factor for LRC (p=0.003), DFS (p=0.01), and OS (p=0.005).
CONCLUSION: Revealing the significant prognostic value of T stage for CCR, LRC, DFS, and OS in the multivariate analysis, we consider that the implementation of intensity modulated radiotherapy (IMRT) and the adoption of intensified concurrent chemoradiotherapy (CCRT), sequential therapy, and targeted therapy should be strongly advocated in order to improve outcome in patients with locally advanced HPSCC.

Popescu B, Popescu CR, Grigore R, et al.
Morphology and morphopathology of hypopharyngo-esophageal cancer.
Rom J Morphol Embryol. 2012; 53(2):243-8 [PubMed]

Cervical esophageal cancer and hypopharyngeal cancer represent a major diagnostic issue in early stages, considering the fact that the implication of both cervical esophageal and hypopharyngeal cancers shows a poor prognostic from the very beginning. Positive diagnosis can only be made after histopathological analysis and immunohistochemical analysis in addition. The bioptic material is sampled by rigid endoscopy this being the only viable method of assessing data on the tumor prior to the surgery. As much as 95% of tumors located at this site are epidermoid carcinomas with different staging and characteristics, other types of tumors being adenocarcinomas, lymphomas, etc. Several risk factors influence the biology of this site thus inflicting both cellular and molecular modifications that are the origin of cancer development.

Urosevic-Maiwald M, Harr T, French LE, Dummer R
Stevens-Johnson syndrome and toxic epidermal necrolysis overlap in a patient receiving cetuximab and radiotherapy for head and neck cancer.
Int J Dermatol. 2012; 51(7):864-7 [PubMed]

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe and life-threatening adverse drug reactions. Herein we report about a patient with head and neck cancer, who developed SJS-TEN overlap after having received cetuximab and radiotherapy. To date, there are only two reports of TEN associated with cetuximab therapy in patients with cancer. Every skin condition in a patient with cancer leading to extensive exfoliation of the skin should alert the oncologist of a possibility of drug-induced SJS or TEN.

Wilson DD, Rahimi AS, Saylor DK, et al.
p16 not a prognostic marker for hypopharyngeal squamous cell carcinoma.
Arch Otolaryngol Head Neck Surg. 2012; 138(6):556-61 [PubMed]

OBJECTIVE: To investigate the prognostic significance of p16 in patients with hypopharyngeal squamous cell carcinoma (HPSCC) and to evaluate the relationship between p16 and human papillomavirus (HPV). Unlike in oropharyngeal SCC (OPSCC), the prognostic significance of p16 in HPSCC and its association with HPV is unclear.
DESIGN: Retrospective medical chart review.
SETTING: University tertiary referral center.
PATIENTS: A total of 27 patients with HPSCC treated with definitive radiation therapy between 2002 and 2011 whose tissue was available for immunohistochemical analysis.
INTERVENTIONS: Twenty-two patients were treated with chemoradiation, and 5 with radiation alone. All tumor biopsy specimens were analyzed for p16 and, when sufficient tissue was available, for HPV DNA.
MAIN OUTCOME MEASURES: Overall survival (OS), locoregional control (LRC), disease-free survival (DFS), and laryngoesophageal dysfunction-free survival (LEDFS) were analyzed according to p16 status.
RESULTS: Findings for p16 were positive in 9 tumors and negative in 18 tumors. Median follow-up was 29.3 months. There was no significant difference in OS, LRC, DFS, or LEDFS for patients with p16-positive vs p16-negative tumors. Only 1 of the 19 tumors tested for HPV was found to be HPV positive. When used as a test for HPV, p16 had a positive predictive value of 17%.
CONCLUSIONS: In contrast to OPSCC, p16 expression in patients with HPSCC had a low positive predictive value for HPV and did not predict improved OS, LRC, DFS, or LEDFS. Thus, for HPSCC, p16 is not a prognostic biomarker. Caution must be taken when extrapolating the prognostic significance of p16 in patients with OPSCC to patients with head and neck SCC of other subsites.

Huscher C, Mingoli A, Mereu A, Sgarzini G
Pharyngolaryngo-esophagectomy with laparoscopic gastric pull-up: a reappraisal for the pharyngoesophageal junction cancer.
Ann Surg Oncol. 2012; 19(9):2980 [PubMed]

BACKGROUND: Surgical treatment of advanced hypopharyngeal tumors is still a surgical challenge. We report a case of a hypopharyngeal tumor treated with a pharyngolaryngo-esophagectomy (PLE) and laparoscopic gastric tubulization and interposition.
METHODS: A 56-year-old man presented with a relapsing hypopharynx carcinoma, after primary chemoradiation therapy. Preoperative workup showed a stage IV cancer with esophageal invasion and multiple cervical lymph node metastases. Surgical treatment consisted of a cervical phase, with larynx, pharynx, and esophagus dissection, radical lymph node dissection, homolateral hemithyroidectomy and definitive tracheostomy, and an abdominal phase with a 4-trocar laparoscopy. The gastrocolic ligament was opened, and short gastric and left gastric vessels were divided preserving an accessory left hepatic artery. Gastric tailoring was carried out with 45-mm linear staplers. The hiatus was opened and the esophagus dissected free with Ultracision (Ethicon Endo-Surgery, Cincinnati, OH) to the tracheal bifurcation. The upper esophagus was bluntly mobilized by finger and sponge stick dissection. The gastric tube was pulled up, and the anastomosis between the stomach and the tongue base was performed with a 2-layer interrupted hand-sewn technique.
RESULTS: Total operative time was 390 min (abdominal time 180 min). Estimated blood loss was 400 cc. The number of dissected cervical lymph nodes was 32. Oral feeding was started after 10 days, and the patient was discharged after 14 days. Stage of disease was pT4N1M0 G3 R0.
CONCLUSIONS: Laparoscopic surgery allows a minimally invasive gastric tailoring and tubulization and transhiatal esophageal dissection and represents a valuable alternative for intestinal reconstruction after PLE. CT scan showing a large hypopharynx carcinoma involving cervical lymph nodes and cervical esophagus.

Wang JX, Zhang YY, Yu XM, et al.
Role of centromere protein H and Ki67 in relapse-free survival of patients after primary surgery for hypopharyngeal cancer.
Asian Pac J Cancer Prev. 2012; 13(3):821-5 [PubMed]

PURPOSE: Centromere protein H (CENP-H) and Ki67 are overexpressed in some malignancies, but whether they are predictors of survival after primary resection for hypopharyngeal squamous cell carcinoma (HSCC) remains unknown.
METHODS: We assessed immunohistochemical expression of CENP-H and Ki67 in 112 HSCC specimens collected between March 2003 and March 2005 for analysis by clinical characteristics. The Kaplan-Meier method was used to analyze relapse-free survival and logistic multivariate regression to determine risk factors of relapse-free survival. Cholecystokinin octapeptide assays and flow cytometry were used to examine cell proliferation and apoptosis after siRNA inhibition of CENP-H in HSCC cells.
RESULTS: Overall, 50 (44.6%) HSCC specimens showed upregulated CENP-H expression and 69 (61.6%) upregulated Ki67. An increased CENP-H protein level was associated with advanced cancer stage and alcohol history (P=0.012 and P=0.048, respectively) but an increased Ki67 protein level only with advanced cancer stage (P=0.021). Increased CENP-H or Ki67 were associated with short relapse-free survival (P<0.001 or P=0.009, respectively) and were independent predictors of relapse-free survival (P=0.001 and P=0.018, respectively). siRNA knockdown of CENP-H mRNA inhibited cell proliferation and promoted cancer cell apoptosis in vitro.
CONCLUSIONS: Upregulated CENP-H and Ki67 levels are significantly associated with short relapse-free survival in HSCC. These factors may be predictors of a relapsing phenotype in HSSC cases.

Barroso Ribeiro R, Ribeiro Breda E, Fernandes Monteiro E
Prognostic significance of nodal metastasis in advanced tumors of the larynx and hypopharynx.
Acta Otorrinolaringol Esp. 2012 Jul-Aug; 63(4):292-8 [PubMed]

OBJECTIVES: To estimate the relevance of post-surgical neck nodal classification (pN) on the global survival of patients with advanced tumors of the larynx and hypopharynx, primarily treated with surgery including neck dissection (ND). To understand the prognostic significance of metastatic lymph nodes' extracapsular spread (ECS) and its impact on survival.
MATERIAL AND METHODS: A retrospective review of patients primarily submitted for total laryngectomy (TL) with either elective or therapeutic bilateral ND. Overall and disease-free survival was analysed according to post-operative histopathological ND results, concerning the presence or absence of nodal involvement, number of affected nodes and the existence of ECS.
RESULTS: One hundred and twenty patients met the inclusion criteria of this study. Concerning nodal involvement, the histopathological evaluation demonstrated positive lymph nodes in 46.6% of the cN0 patients. The rate of patients alive after 2 years of follow-up, based on pN analysis, was 88.1% for the pN0 group, 65.4% for the group N+ without ECS, 46.2% for the N+ ECS+ (1 node) and 15.4% for the N+ ECS+ (more than 1 node) group (P<.001).
CONCLUSIONS: This study demonstrates a high prevalence of occult neck disease in tumours of the larynx and hypopharynx. The involvement of metastatic cervical lymph nodes has a negative impact on survival. Patients with multinodal ECS have a poorer survival, reflected by a higher rate of loco-regional and distant metastases, when compared to ECS in one single lymph node.

Schneider R, Leinung S, Aust W, Jonas S
Papillary carcinoma in a thyroglossal duct cyst: management and algorithm for treatment of a rare entity.
Acta Chir Belg. 2012 Mar-Apr; 112(2):167-9 [PubMed]

Thyroglossal duct cyst carcinoma is a very rare finding and its presentation is similar to that of a benign cyst, which is the most common congenital lesions of the neck. The diagnosis is usually made postoperatively after histological examination. A case of a surgically treated 47-year-old patient with a papillary carcinoma in a thyroglossal duct cyst is presented. The patient underwent the Sistrunk procedure. After stratification in the proposed high risk group, subsequent total thyroidectomy and radioiodine therapy were performed successfully. The patient remains tumor-free 18 months postoperatively. Sistrunk procedure is recommended as the most promising treatment generally including total thyroidectomy with or without lymph node dissection. Subsequent radiotherapy is recommended in selected patients, depending on the classification into high- or low-risk patients. Diagnostic and therapeutic features are discussed with the current literature and a definitive algorithm for treatment based on risk group stratification is proposed.

Brook I
Eating again: a physician's personal experience after laryngectomy.
Nutr Cancer. 2012; 64(5):635-6 [PubMed]

This article presents the author's personal experiences in eating again after becoming a laryngectomee. He was diagnosed with hypopharyngeal carcinoma and underwent total laryngectomy with a free flap reconstruction. The personal story is told in the hope that nutritionists and other health care providers will realize the difficult challenges in obtaining adequate nutrition that a patient diagnosed with cancer who undergoes laryngectomy must face. These include the effects of radiation treatment and surgery, which create functional and anatomical changes that make swallowing difficult.

Lefebvre JL, Andry G, Chevalier D, et al.
Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891.
Ann Oncol. 2012; 23(10):2708-14 [PubMed] Article available free on PMC after 01/10/2013

BACKGROUND: We report the 10-year results of the EORTC trial 24891 comparing a larynx-preservation approach to immediate surgery in hypopharynx and lateral epilarynx squamous cell carcinoma.
MATERIAL AND METHODS: Two hundred and two patients were randomized to either the surgical approach (total laryngectomy with partial pharyngectomy and neck dissection, followed by irradiation) or to the chemotherapy arm up to three cycles of induction chemotherapy (cisplatin 100 mg/m(2) day 1 + 5-FU 1000 mg/m(2) day 1-5) followed for complete responders by irradiation and otherwise by conventional treatment. The end points were overall survival [OS, noninferiority: hazard ratio (preservation/surgery) ≤ 1.428, one-sided α = 0.05], progression-free survival (PFS) and survival with a functional larynx (SFL).
RESULTS: At a median follow-up of 10.5 years on 194 eligible patients, disease evolution was seen in 54 and 49 patients in the surgery and chemotherapy arm, respectively, and 81 and 83 patients had died. The 10-year OS rate was 13.8% in the surgery arm and 13.1% in the chemotherapy arm. The 10-year PFS rates were 8.5% and 10.8%, respectively. In the chemotherapy arm, the 10-year SFL rate was 8.7%.
CONCLUSION: This strategy did not compromise disease control or survival (that remained poor) and allowed more than half of the survivors to retain their larynx.