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Hypopharyngeal Cancer

3 sections of the pharnx The hypopharynx is the bottom part of the pharynx (throat). The hypopharynx is sometimes also known as the laryngopharynx. Hypopharyngeal cancer occurs when the cells of the hypopharnx become abnormal and start growing in an uncontrolled way. The majority of hypopharyngeal cancers are squamous cell carcinomas (squamous cells are the thin, flat cells in the lining of the hypopharynx), but there are a number of other different types.

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Latest Research Publications

Information Patients and the Public (6 links)


Information for Health Professionals / Researchers (5 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Koizumi M, Takahashi M, Murata M, et al.
Thrombotic microangiopathy associated with cetuximab, an epidermal growth factor receptor inhibitor
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Clin Nephrol. 2017; 87 (2017)(1):51-54 [PubMed] Related Publications
Cetuximab is a chimeric human-murine monoclonal antibody that binds competitively and with high affinity to the epidermal growth factor receptor (EGFR) and is used to treat advanced squamous cell carcinoma of the head and neck. After receiving a total of six doses of cetuximab, a 72-year-old male presented with pretibial edema, acne-like skin rash, and nephrotic syndrome. The renal biopsy findings revealed features of thrombotic microangiopathy (TMA), with the expansion of the subendothelial zone, reduplication of the glomerular basement, and swelling of the endothelial cells. Nine weeks after the discontinuation of cetuximab, his pretibial edema had disappeared and proteinuria decreased. To our knowledge, this is the first report in which kidney biopsy revealed evidence of TMA due to cetuximab administration. Our report suggests that it may be prudent to monitor patients receiving cetuximab closely for the possible development of nephrotic syndrome.
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Shirai K, Saitoh JI, Musha A, et al.
Clinical Outcomes of Definitive and Postoperative Radiotherapy for Stage I-IVB Hypopharyngeal Cancer.
Anticancer Res. 2016; 36(12):6571-6578 [PubMed] Related Publications
BACKGROUND: Hypopharyngeal cancer is relatively rare disease and continues to have a poor prognosis. This study analyzed the efficacy and safety of radiotherapy for stage I-IVB hypopharyngeal cancer.
PATIENTS AND METHODS: Between 2000 and 2015, 72 patients were treated with definitive radiotherapy and 29 patients with stage IVA were treated with postoperative radiotherapy.
RESULTS: With definitive radiotherapy, the 3-year locoregional control rates for stage I-II, III, IVA, and IVB disease were 89%, 74%, 51% and 0%, respectively. The 3-year overall survival rates for patients with stage I-II, III, IVA and IVB disease were 84%, 89%, 55% and 15%, respectively. In patients with stage IVA disease treated with postoperative radiotherapy, 3-year locoregional control and overall survival rates were 83% and 75%, respectively, which were significantly better than those treated with definitive radiotherapy.
CONCLUSION: Definitive radiotherapy was effective for stage I-III disease. Surgery and postoperative radiotherapy improved the survival rate of patients with stage IVA hypopharyngeal cancer.

Wang Q, Liu Y, Hu G, et al.
The survival rate and larynx preservation in elderly cancer patients who received surgical operation: A retrospective cohort study.
Int J Surg. 2016; 36(Pt A):342-346 [PubMed] Related Publications
BACKGROUND: To investigate the efficiency of surgical operation for patients over 70 years with hypopharyngeal cancer.
MATERIALS AND METHODS: A retrospective analysis of the medical records from 68 patients over 70 years-old with hypopharyngeal cancer who underwent different therapeutic regimen between 2000 and 2009 was conducted. 36 of 68 patients underwent larynx preservation. All patients were treated with surgical operation and adjuvant radiotherapy. A Kaplan-Meier method was employed to calculate the survival rate.
RESULTS: Overall 3 year-and 5 year-survival rates were 48.6% and 29.4% respectively. For patients who underwent larynx preservation, 5 year-survival rate was 30.5%, which was decreased compared to 3 year-survival rate (46.9%) However, 3 year- and 5 year-survival rates in patients without larynx preservation were 46.9% and 28.1% respectively, suggesting that no statistically significant difference of survival rates was found between patients with or without larynx preservation (P > 0.05). A majority of patients who receive larynx preservation exhibited normal breathing and eating abilities and could present an intelligible speech. 16 of 36 patients who preserved larynx and 14 of 32 patients who underwent laryngectomy showed postoperative complication. No significant difference was observed in these two treatments, indicating larynx preservation is not a factor for inducing complication.
CONCLUSION: This study provides evidence that the quality of life for elderly patients with hypopharyngeal cancer can be improved by optimizing the therapeutic regimen based on the physical condition of each patient.

Pracy P, Loughran S, Good J, et al.
Hypopharyngeal cancer: United Kingdom National Multidisciplinary Guidelines.
J Laryngol Otol. 2016; 130(S2):S104-S110 [PubMed] Free Access to Full Article Related Publications
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. With an age standardised incidence rate of 0.63 per 100 000 population, hypopharynx cancers account for a small proportion of the head and neck cancer workload in the UK, and thus suffer from the lack of high level evidence. This paper discusses the evidence base pertaining to the management of hypopharyngeal cancer and provides recommendations on management for this group of patients receiving cancer care. Recommendations • Cross-sectional imaging with computed tomography of the head, neck and chest is necessary for all patients; magnetic resonance imaging of the primary site is useful particularly in advanced disease; and computed tomography and positron emission tomography to look for distant disease. (R) • Careful evaluation of the upper and lower extents of the disease is necessary, which may require contrast swallow or computed tomography and positron emission tomography imaging. (R) • Formal rigid endoscopic assessment under general anaesthetic should be performed. (R) • Nutritional status should be proactively managed. (R) • Full and unbiased discussion of treatment options should take place to allow informed patient choice. (G) • Early stage disease can be treated equally effectively with surgery or radiotherapy. (R) • Endoscopic resection can be considered for early well localised lesions. (R) • Bulky advanced tumours require circumferential or non-circumferential resection with wide margins to account for submucosal spread. (R) • Offer primary surgical treatment in the setting of a compromised larynx or significant dysphagia. (R) • Midline lesions require bilateral neck dissections. (R) • Consider management of silent nodal areas usually not addressed for other primary sites. (G) • Reconstruction needs to be individualised to the patients' needs and based on the experience of the unit with different reconstructive techniques. (G) • Consider tumour bulk reduction with induction chemotherapy prior to definitive radiotherapy. (R) • Consider intensity modulated radiation therapy where possible to limit the consequences of wide field irradiation to a large volume. (R) • Use concomitant chemotherapy in patients who are fit enough and consider epidermal growth factor receptor blockers for those who are less fit. (R).

Lim RS, Evans L, George AP, et al.
Do demographics and tumour-related factors affect nodal yield at neck dissection? A retrospective cohort study.
J Laryngol Otol. 2017; 131(S1):S36-S40 [PubMed] Related Publications
BACKGROUND: Nodal metastasis is an important prognostic factor in head and neck squamous cell carcinoma. This study aimed to determine the average nodal basin yield per level of neck dissection, and to investigate if age, gender, body mass index, tumour size, depth of tumour invasion and p16 status influence nodal yield.
METHOD: A retrospective review of 185 patients with head and neck squamous cell carcinoma generated 240 neck dissection specimens.
RESULTS: The respective mean nodal yields for levels I, II, III, IV and V were 5.27, 9.43, 8.49, 7.43 and 9.02 in non-cutaneous squamous cell carcinoma patients, and 4.2, 7.57, 9.65, 4.33 and 12.29 in cutaneous squamous cell carcinoma patients. Multiple regression analysis revealed that p16-positive patients with mucosal squamous cell carcinoma yielded, on average, 2.4 more nodes than their p16-negative peers (p = 0.04, 95 per cent confidence interval = 0.116 to 4.693). This figure was 3.84 (p = 0.008, 95 per cent confidence interval = 1.070 to 6.605) for p16-positive patients with oral cavity squamous cell carcinoma.
CONCLUSION: In mucosal squamous cell carcinoma, p16-positive status significantly influenced nodal yield, with the impact being more pronounced in oral cavity squamous cell carcinoma patients.

Jager EA, Ligtenberg H, Caldas-Magalhaes J, et al.
Validated guidelines for tumor delineation on magnetic resonance imaging for laryngeal and hypopharyngeal cancer.
Acta Oncol. 2016; 55(11):1305-1312 [PubMed] Related Publications
BACKGROUND: Validation of magnetic resonance imaging (MRI) and development of guidelines for the delineation of the gross tumor volume (GTV) is of utmost importance to benefit from the visibility of anatomical details on MR images and to achieve an accurate GTV delineation. In the ideal situation, the GTV delineation corresponds to the histopathologically determined 'true tumor volume'. Consequently, we developed guidelines for GTV delineation of laryngeal and hypopharyngeal tumors on MRI and determined the accuracy of the resulting delineation of the tumor outline on histopathology as gold standard.
MATERIAL AND METHODS: Twenty-seven patients with T3 or T4 laryngeal/hypopharyngeal cancer underwent a MRI scan before laryngectomy. Hematoxylin and eosin sections were obtained from surgical specimens and tumor was delineated by one pathologist. GTV was delineated on MR images by three independent observers in two sessions. The first session (del1) was performed according to clinical practice. In the second session (del2) guidelines were used. The reconstructed specimen was registered to the MR images for comparison of the delineated GTVs to the tumor on histopathology. Volumes and overlap parameters were analyzed. A target margin needed to assure tumor coverage was determined.
RESULTS: The median GTVs (del1: 19.4 cm(3), del2: 15.8 cm(3)) were larger than the tumor volume on pathology (10.5 cm(3)). Comparable target margins were needed for both delineation sessions to assure tumor coverage. By adding these margins to the GTVs, the target volumes for del1 (median: 81.3 cm(3)) were significantly larger than for del2 (median: 64.2 cm(3)) (p ≤ 0.0001) with similar tumor coverage.
CONCLUSIONS: In clinical radiotherapy practice, the delineated GTV on MRI is twice as large as the tumor volume. Validated delineation guidelines lead to a significant decrease in the overestimation of the tumor volume.

Lee JH, Jeong JS, Kim SR, Lee YC
Small cell carcinoma of the pyriform sinus successfully treated with concurrent chemo-radiotherapy: A case report.
Medicine (Baltimore). 2016; 95(36):e4759 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Primary small cell carcinomas (SCCs) are uncommon in extrapulmonary sites and account for only 2.5% to 5.0% of all SCCs. SCCs in the pyriform sinus are rare and there is little information regarding this disease, especially on therapeutics. Herein, we present a case of successfully treated SCC in the right pyriform sinus that occurred in a patient with small cell lung carcinoma (SCLC) that completely resolved 4 years prior.
METHODS: A 1.5 × 1.5-cm mass in the right pyriform sinus was detected on imaging studies in a 71-year-old male at a regular check-up visit after being in remission from SCLC.
RESULTS: Based on histologic examination and immunohistochemistry, the tumor in the right pyriform sinus was diagnosed as an extrapulmonary SCC. Chemo-radiotherapy was applied to the SCC of the pyriform sinus with a regimen of etoposide and cisplatin. The patient exhibited complete response to treatment and has been disease free for 11 months.
CONCLUSION: This interesting case shows that chemotherapy with concurrent radiation may be an effective therapeutic modality for localized extrapulmonary SCC similar to localized SCLC, which is treated with concurrent chemo-radiotherapy as the standard therapeutic option.

Chen F, Chen C, Qu Y, et al.
Selenium-binding protein 1 in head and neck cancer is low-expression and associates with the prognosis of nasopharyngeal carcinoma.
Medicine (Baltimore). 2016; 95(35):e4592 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Selenium-binding protein 1 (SELENBP1) expression is reduced markedly in many types of cancers and low SELENBP1 expression levels are associated with poor patient prognosis.
METHODS: SELENBP1 gene expression in head and neck squamous cell carcinoma (HNSCC) was analyzed with GEO dataset and characteristics of SELENBP1 expression in paraffin embedded tissue were summarized. Expression of SELENBP1 in nasopharyngeal carcinoma (NPC), laryngeal cancer, oral cancer, tonsil cancer, hypopharyngeal cancer and normal tissues were detected using immunohistochemistry, at last, 99 NPC patients were followed up more than 5 years and were analyzed the prognostic significance of SELENBP1.
RESULTS: Analysis of GEO dataset concluded that SELENBP1 gene expression in HNSCC was lower than that in normal tissue (P < 0.01), but there was no significant difference of SELENBP1 gene expression in different T-stage and N-stage (P > 0.05). Analysis of pathological section concluded that SELENBP1 in the majority of HNSCC is low expression and in cancer nests is lower expression than surrounding normal tissue, even associated with the malignant degree of tumor. Further study indicated the low SELENBP1 expression group of patients with NPC accompanied by poor overall survival and has significantly different comparing with the high expression group.
CONCLUSION: SELENBP1 expression was down-regulated in HNSCC, but has no associated with T-stage and N-stage of tumor. Low expression of SELENBP1 in patients with NPC has poor over survival, so SELENBP1 could be a novel biomarker for predicting prognosis.

Wakasaki T, Gotoh S, Tomonobe E, et al.
Posterior Reversible Encephalopathy Syndrome During Combined Modality Therapy for Head and Neck Squamous Cell Carcinoma.
Ann Otol Rhinol Laryngol. 2016; 125(10):844-9 [PubMed] Related Publications
OBJECTIVES: Posterior reversible encephalopathy syndrome (PRES) is a rare and acute disease with central nervous system symptoms. Without appropriate therapy, patients may exhibit a poor prognosis. PRES should be recognized as a possible problem during therapy for head and neck squamous cell carcinoma (HNSCC).
METHODS: A 56-year-old female developed PRES during combined modality therapy for HNSCC. On the fourth day after surgery and following chemoradiotherapy, PRES developed with a sudden visual disorder, followed by headache located at the back of the head and convulsions accompanied by impaired consciousness. We diagnosed PRES based on the clinical manifestations and magnetic resonance imaging data.
RESULTS: The patient recovered from PRES by appropriate treatment.
CONCLUSION: This is the first case report of PRES developed during treatment for HNSCC. Masked by other cerebrovascular disorders, more cases of PRES could exist than usually expected; therefore, we should consider PRES as a differential diagnosis for central nervous system disorders developing during high-intensity therapy.

Koopmann M, Weiss D, Steiger M, et al.
Thyroid cartilage invasion in laryngeal and hypopharyngeal squamous cell carcinoma treated with total laryngectomy.
Eur Arch Otorhinolaryngol. 2016; 273(11):3789-3794 [PubMed] Related Publications
The objective of this study is to analyze the accuracy of computed tomography in detecting malignant thyroid cartilage invasion. In a retrospective chart review, 120 patients with carcinoma of the larynx and hypopharynx underwent computed tomography before total laryngectomy. These data were compared with the histological specimens. Multidetector computed tomography (MDCT) scan had a positive predictive value (PPV) of 76 % and a negative predictive value (NPV) of 69 %. The specificity of MDCT was 89 % and sensitivity was 46 %. Comparison between radiologic suspected cartilage invasion and histologic results showed a significant correlation (p < 0.02). We found no significant impact of cartilage invasion concerning survival rates (5-year overall survival p = 0.683; 5-year disease-free survival p = 0.711). Preoperative CT scan is an important instrument in detecting neoplastic cartilage invasion.

Joo YH, Cho KJ, Lee YS, et al.
Prognostic impact of perineural invasion in hypopharyngeal squamous cell carcinoma.
Acta Otolaryngol. 2016; 136(10):1069-73 [PubMed] Related Publications
OBJECTIVES: The aim of this study was to evaluate the role of PNI in HPSCC.
METHODS: The medical records of 105 patients who underwent surgery-based treatment for HPSCC were reviewed. Clinicopathologic parameters including disease-specific survival were correlated with PNI.
RESULTS: PNI was identified in 27 of the 105 (25.7%) cases of HPSCC. Correlation analysis demonstrated that PNI in HPSCC was significantly correlated with pN classification (10.3% in N0/N1 vs 34.8% in N2/N3, p = 0.006). Patients with PNI had decreased 5-year disease-specific survival with borderline significance (p = 0.065). In a sub-set of 31 patients who did not receive post-operative radiotherapy, PNI was determined to be a significant prognostic predictor (p = 0.033). In multivariate analysis, extracapsular invasion was the only independent prognostic factor for disease-specific survival (p = 0.001).
CONCLUSION: Perineural invasion (PNI) should be considered an independent predictor for cervical lymph node involvement. PNI status in primary hypopharyngeal squamous cell carcinoma (HPSCC) specimens should be considered in decisions concerning adjuvant radiotherapy.

Imai T, Goto T, Matsumoto K, et al.
Late-onset dysphagia caused by severe spastic peristalsis of a free jejunal graft in a case of hypopharyngeal cancer.
Auris Nasus Larynx. 2016; 43(6):693-7 [PubMed] Related Publications
Free jejunal transfer is the main technique used for reconstructing a circumferential defect caused by total pharyngo-laryngo-cervical-esophagectomy in certain cancer cases. We report a rare case of severe late-onset dysphagia caused by autonomous spastic peristalsis, which led to complete obstruction of the free jejunal route. A 70-year-old man underwent treatment for hypopharyngeal cancer involving total pharyngolaryngectomy with free jejunal transfer. After uneventful peri- and postoperative recovery, he developed sudden-onset severe dysphagia 22 months later. Gastrografin fluoroscopy revealed abnormal peristalsis and contraction of the transferred jejunum, leading to complete obstruction. Nutritional treatment, application of depressants of peristalsis, and xylocaine injection into the outer space of the jejunal mucosa all failed to alleviate the dysphagia. Surgical treatment involving a longitudinal incision of the jejunal graft, and interposing a cutaneous flap, as a fixed wall, between the incised jejunal margins to prevent obstruction was performed. After further reconstructive surgery involving using a pectoralis major musculocutaneous flap and a split-thickness skin graft to close a refractory jejunum-skin fistula, the dysphagia was permanently alleviated. To our knowledge, this is the first report of severe dysphagia caused by peristalsis of a free jejunal graft.

Zhang C, Zhu M, Chen M, et al.
Free flap combined with pectoralis major flap for reconstruction after total laryngopharyngectomy in patients with advanced hypopharyngeal carcinoma.
Acta Otolaryngol. 2016; 136(8):841-6 [PubMed] Related Publications
CONCLUSION: The findings suggest that a pectoralis major flap combined with a free flap is a safe and reliable method of reconstruction after total pharyngolaryngectomy; with this technique, one can help these patients remain disease free, with normal swallowing function, for a relatively acceptable survival duration.
OBJECTIVES: To determine the functional and oncological outcomes of a combined flap for the extensive defects after total pharyngolaryngectomy in patients with advanced squamous cell carcinoma of the hypopharynx (SCCHP).
METHOD: This study determined the perioperative morbidity and functional and oncologic outcomes of 21 patients with advanced SCCHP who underwent total laryngopharyngectomy and reconstruction using a combination of a pectoralis major flap and a free flap.
RESULTS: The free flap and pectoralis major flap were used to reconstruct the defects for all 21 patients. Fourteen patients were reconstructed with jejunal free flaps and pectoralis major flaps; in the remaining seven patients, anterolateral thigh flaps and pectoralis major flaps were used. All the combined flaps worked well, and patients recovered normal swallowing function a mean 19.4 days after surgery. After an overall mean follow-up time of 31.3 months, 30% of patients were still alive at the time of this analysis, with no evidence of disease.

Wakisaka N, Hirai N, Kondo S, et al.
T-status and an oral fluoropyrimidine, S-1, adjuvant chemotherapy are prognostic factors in reduced-RADPLAT for resectable hypopharyngeal cancer.
Acta Otolaryngol. 2016; 136(8):834-40 [PubMed] Related Publications
CONCLUSION: Reduced-RADPLAT for HPC achieved comparative survival and locoregional control rates with lower toxicities compared with concurrent chemoradiotherapies including original RADPLAT. S-1 adjuvant chemotherapy showed a survival benefit.
OBJECTIVES: To evaluate the efficacy and toxicities of targeted intra-arterial (IA) infusion of cisplatin with concurrent radiotherapy with a reduced dose (reduced-RADPLAT) for resectable hypopharyngeal cancer (HPC).
METHODS: Between 1999-2012, 50 patients with stage II-IVA HPC primarily treated by reduced-RADPLAT were analyzed. They were treated by 2-5 courses of IA cisplatin infusion (100 mg per body) with simultaneous systemic infusion of sodium thiosulfate concurrent with conventional radiotherapy (66-70 Gy). After 2003, S-1, an oral fluoropyrimidine, adjuvant chemotherapy was administered to all eligible patients.
RESULTS: During a median follow-up of 48.6 months, the estimated 3- and 5-year overall survival (OS), progression-free survival (PFS), locoregional control, and laryngoesophageal dysfunction-free survival (LEDFS) rates were 76.0% and 62.0%, 58.0% and 50.0%, 66.0% and 62.0%, and 56.0% and 54.0%, respectively. Grade 3 toxicities were observed in 30.0%. No patient had grade 4 or higher toxicities. No patient required tube feeding or tracheotomy at 3 months after treatment. T4-lesions and S-1 administration were significant factors predicting poor and good OS, PFS, and LEDFS, respectively.

Hoch S, Bohne F, Franke N, et al.
Extent of Salvage Neck Dissection in Advanced Oro- and Hypopharyngeal Cancer.
Anticancer Res. 2016; 36(3):981-6 [PubMed] Related Publications
BACKGROUND/AIM: Primary radiochemotherapy (RCT) is becoming increasingly important in patients with oro- and hypopharyngeal cancer. However, debate exists on the extent of salvage neck dissection (ND) in those patients. The purpose of the present study was to evaluate the regional control after salvage ND.
PATIENTS AND METHODS: Clinical, histological and radiological data, results of 51 patients with oro- or hypopharyngeal cancer and N2 neck who underwent selective ND in case of radiological evidence of residual neck disease, were retrospectively analyzed.
RESULTS: Altogether 52 metastases were detected in 20 (39.2%) patients by histological examination. They were localized in level II (n=23), III (n=13), IV (n=11) and V (n=5). Regional recurrence occurred in 4 patients (7.8%) in previous dissected neck levels in the follow-up.
CONCLUSION: Selective ND of suspicious neck levels for residual disease after RCT of oro- and hypopharyngeal cancer seems to be a sufficient treatment.

Guo W, Luo D, Lin M, et al.
Pretreatment Intra-Voxel Incoherent Motion Diffusion-Weighted Imaging (IVIM-DWI) in Predicting Induction Chemotherapy Response in Locally Advanced Hypopharyngeal Carcinoma.
Medicine (Baltimore). 2016; 95(10):e3039 [PubMed] Free Access to Full Article Related Publications
The aim of this study was to predict response to induction chemotherapy in patients with locally advanced hypopharyngeal carcinoma by IVIM values.Twenty-eight patients with locally advanced hypopharyngeal carcinoma underwent IVIM studies using 12 different b values (b = 0, 10, 20, 30, 50, 70 100, 150, 200, 400, 800, and 1000 s/ mm). All patients underwent 2 MRI studies: a baseline exam before any treatment and a mid-treatment exam 3 weeks after induction chemotherapy. In the IVIM approach, D, f, and D were extracted from a bi-exponential fit. For comparison, the ADC map were extracted from a mono-exponential fit. At the end of induction chemotherapy, patients were classified as responders or nonresponders group according to the Response Evaluation Criteria in Solid Tumors criteria (RECIST), based on their MRI measurement. The patients were classified into high grade group (G1), moderate grade group (G2), and low grade group (G3) according to the tumor pathological grading. The predictive value of IVIM parameters were examined with Student's t test, analysis of variance (ANOVA), and receiver operating characteristic (ROC) curves.After 2 cycles of induction chemotherapy, 18 patients were categorized into the responder group whereas the other 10 patients were considered nonresponders. Compared with the pretreatment value, the post-treatment ADC value and D value was significantly higher and the posttreatment D value was significantly lower (all P <  0.05). In contrast, post-treatment f parameter only changed slightly (P > 0.05). Compared with nonresponders, a notably lower pretreatment ADC value, D value, posttreatment D value, and higher posttreatment ADC value, D value, ΔADC, ΔD, and ΔD were observed in responders (all P < 0.05), but no significant change in Δ f among the 2 group (P > 0.05). The ROC curve analysis indicated that the cutoff of pretreatment D value in best predicting tumor's chemotherapeutic response was 0.847 × 10 mm/s, and the corresponding AUC, sensitivity, and specificity were 0.806, 75.0%, and 88.9%, respectively. Although pretreatment IVIM-derived parameters had no significant differences between high grade, moderate grade, and low grade group, a trend towards lower D was observed with increasing tumor grading from G3 to G1.IVIM-DWI can potentially predict the treatment response to induction chemotherapy for hypopharyngeal carcinoma.

Ng SH, Liao CT, Lin CY, et al.
Dynamic contrast-enhanced MRI, diffusion-weighted MRI and (18)F-FDG PET/CT for the prediction of survival in oropharyngeal or hypopharyngeal squamous cell carcinoma treated with chemoradiation.
Eur Radiol. 2016; 26(11):4162-4172 [PubMed] Related Publications
OBJECTIVES: We prospectively investigated the roles of pretreatment dynamic contrast-enhanced MR imaging (DCE-MRI), diffusion-weighted MR imaging (DWI) and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG PET)/CT for predicting survival of oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) patients treated with chemoradiation.
METHODS: Patients with histologically proven OHSCC and neck nodal metastases scheduled for chemoradiation were eligible. Clinical variables as well as DCE-MRI-, DWI- and (18)F-FDG PET/CT-derived parameters of the primary tumours and metastatic neck nodes were analysed in relation to 3-year progression-free survival (PFS) and overall survival (OS) rates.
RESULTS: Eighty-six patients were available for analysis. Multivariate analysis identified the efflux rate constant (K ep)-tumour < 3.79 min(-1) (P = 0.001), relative volume of extracellular extravascular space (V e)-node < 0.23 (P = 0.004) and SUVmax-tumour > 19.44 (P = 0.025) as independent risk factors for both PFS and OS. A scoring system based upon the sum of each of the three imaging parameters allowed stratification of our patients into three groups (patients with 0/1 factor, patients with 2 factors and patients with 3 factors, respectively) with distinct PFS (3-year rates = 72 %, 38 % and 0 %, P < 0.0001) and OS (3-year rates = 81 %, 46 % and 20 %, P < 0.0001).
CONCLUSIONS: K ep-tumour, V e-node and SUVmax-tumour were independent prognosticators for OHSCC treated with chemoradiation. Their combination helped survival stratification.
KEY POINTS: • K ep -tumour, V e -node and SUV max -tumour are independent predictors of survival rates. • The combination of these three prognosticators may help stratification of survival. • MRI and FDG-PET/CT play complementary roles in prognostication of head and neck cancer.

Gupta V, Sharma AK, Pattnaik B, Kudria KC
Spontaneous ante-grade enteral migration of jejunostomy tube: A rare complication.
J Cancer Res Ther. 2015 Oct-Dec; 11(4):1033 [PubMed] Related Publications
Ante-grade migration of a feeding jejunostomy tube is a rare occurrence. A 47-year-old lady with hypopharyngeal malignancy underwent surgical placement of jejunostomy tube. Eight months later, she came with disappearance of the tube from skin surface. Clinical examination revealed skin erosion and disappearance of previously placed tube. Abdominal radiograph showed radio.opaque tube in the abdomen in its entirety. The patient underwent reoperation to establish enteral feeding route and at the same time retrograde extraction of the tube (from proposed site for placement of jejunostomy tube). Use of proper fixation, placement of tube with dilated distal ends can potentially prevent these complications.

Huang YC, Lee YC, Tseng PH, et al.
Regular screening of esophageal cancer for 248 newly diagnosed hypopharyngeal squamous cell carcinoma by unsedated transnasal esophagogastroduodenoscopy.
Oral Oncol. 2016; 55:55-60 [PubMed] Related Publications
OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is common in hypopharyngeal squamous cell carcinoma (HSCC) patients. This prospective study is to reveal the prevalence of simultaneous ESCC in newly diagnosed HSCC patients by unsedated transnasal esophagogastroduodenoscopy (EGD) and to analyze the clinical predictors for simultaneous esophageal lesions and their survival.
MATERIALS AND METHODS: 248 patients with newly diagnosed HSCC and without previous head and neck cancer between 2007 and 2014 were prospectively evaluated for HSCC and simultaneous esophageal lesions by unsedated transnasal EGD. The clinical factors for simultaneous esophageal lesions were evaluated. Survival analysis of the HSCC patients receiving complete treatment was done.
RESULTS: The mean age was 58years. 170 HSCC (68.5%) were classified as T3-T4. The procedures were successfully performed (98.4%), except 4 huge tumors. 174 HSCC (85.7%, out of 203 tumors biopsied) were pathologically proved malignancy by this technique. Regarding esophageal lesions (45.5%), ESCC occurred in 36 patients (14.8%), dysplasia without ESCC occurred in 23 (9.4%) and Lugol voiding lesion without ESCC or dysplasia occurred in 52 (21.3%). Alcohol drinking (adjusted OR: 6.95, p<0.05) and N3 classification (adjusted OR: 2.41, p<0.05) of HSCC were the independent risk factors for the presence of esophageal lesions. The overall survival of the HSCC patients with ESCC was significantly lower than those without ESCC (p=0.013).
CONCLUSIONS: Unsedated transnasal EGD is a promising technique for diagnosis of HSCC and simultaneous ESCC. Simultaneous esophageal lesions including ESCC (15%) are common in newly diagnosed HSCC patients, especially with alcohol drinking or N3 disease.

Takehana K, Kodaira T, Tachibana H, et al.
Retrospective analysis of the clinical efficacy of definitive chemoradiotherapy for patients with hypopharyngeal cancer.
Jpn J Clin Oncol. 2016; 46(4):344-9 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
OBJECTIVE: A retrospective analysis was performed to evaluate the clinical efficacy of definitive chemoradiotherapy including intensity-modulated radiotherapy for patients with hypopharyngeal cancer.
METHODS: Previously untreated 204 patients with hypopharyngeal cancer were treated with definitive chemoradiotherapy. Of note, 66-70 Gy was delivered to the primary and involved nodes and 36-54 Gy was delivered to the prophylactic lymph node using standard fractionated radiotherapy. One hundred and forty-six patients received induction chemotherapy as a larynx preservation strategy, followed by definitive radiotherapy with or without concurrent chemotherapy. Intensity-modulated radiotherapy was also performed after 2006.
RESULTS: The median follow-up time of this cohort was 43.4 months (range; 6.9-151.0). The 3-year overall survival, progression-free survival and larynx preservation survival rates were 78.8% (95% confidence interval; 73.0-85.0), 58.4% (95% confidence interval; 51.8-65.9) and 67.5% (95% confidence interval; 61.0-74.7), respectively. Multivariate analyses identified the following significant prognostic factors: an advanced age, the T category and N category for overall survival, the T category and N category for progression-free survival and the T category for larynx preservation survival. Acute toxicities of Grade 3 or higher were observed in 47 patients (23.0%). Two patients (1.0%) had Grade 4 pharyngeal edema. Suspicious treatment-related death due to lethal pharyngeal hemorrhage occurred in 1 (0.4%) patient. The rates of Grade 2 xerostomia in patients treated with intensity-modulated radiotherapy were 28.1, 17.4 and 9.5% at 6 months, 1 and 2 years after the completion of radiotherapy, respectively.
CONCLUSIONS: The efficacy and safety of definitive chemoradiotherapy are considered feasible with sufficient laryngeal preservation.

Vageli DP, Prasad ML, Sasaki CT
Gastro-duodenal fluid induced nuclear factor-κappaB activation and early pre-malignant alterations in murine hypopharyngeal mucosa.
Oncotarget. 2016; 7(5):5892-908 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
We recently described the role of gastro-duodenal fluids (GDFs) in generating changes consistent with hypopharyngeal neoplasia through activation of NF-κB pathway, using an in vitro model of human hypopharyngeal normal keratinocytes. Here, we further provide evidence that gastro-duodenal reflux is a risk factor for early pre-malignant alterations in hypopharyngeal mucosa (HM) related to an activated NF-κB oncogenic pathway, using both an in vitro and a novel in vivo model of C57Bl/6J mice. Histological, immunohistochemical and automated quantitative analysis documents significant NF-κB activation and early pre-malignant alterations in HM topically exposed to GDFs, compared to acid alone and other controls. Early pre-malignant histologic lesions exhibited increased Ki67, CK14 and ΔNp63, cell proliferation markers, changes of cell adhesion molecules, E-Cadherin and β-catenin, and STAT3 activation. The in vivo effect of NF-κB activation is positively correlated with p-STAT3, Ki67, CK14 or β-catenin expression, while GDFs induce significant transcriptional activation of RELA(p65), bcl-2, TNF-α, STAT3, EGFR and wnt5A, in vivo. Our in vivo model demonstrates selectively activated NF-κB in response to topically administrated GDFs, leading to early pre-malignant events in HM.

Qiu X, Chen J, Zhang Z, et al.
Aberrant GRK6 promoter methylation is associated with poor prognosis in hypopharyngeal squamous cell carcinoma.
Oncol Rep. 2016; 35(2):1027-33 [PubMed] Related Publications
Hypopharyngeal squamous cell carcinoma (HSCC) is one of the most common head and neck cancers with high invasiveness and poor prognosis. To identify targeted therapeutics against metastasis, a better understanding of the regulation of HSCC cell invasion is needed. In recent years, G protein-coupled receptor kinases (GRKs) have been implicated in cancer metastasis through phosphorylation of the activated form of G protein coupled receptors (GPCRs). However, there is little information regarding GRKs expression in HSCC. In the present study, we examined GRK6 expression in HSCC and also assessed the possible cause of its aberrant expression, as well as its clinical significance. Real-time quantitative PCR (qPCR) and western blotting were performed to analyze the expression of GRK6 in HSCC tissues and corresponding non-malignant tissues. Subsequently, paired HSCC and corresponding non-malignant tissues were evaluated for the methylation status of GRK6 gene promoter using methylation-specific PCR (MSP). Furthermore, we investigated the methylation status and the clinicopathological significance of GRK6 in 45 paired HSCC and corresponding non-malignant tissues. The suppression of GRK6 in hypopharyngeal cell line FaDu by GRK6-shRNA lentivirus transfection was utilized to detect the role of GRK6 in hypopharyngeal cancer progression. Our results showed that the expression of GRK6 mRNA and protein was significantly lower in HSCC than in corresponding adjacent non-tumor tissues, and this downregulation was found to be in accordance with aberrant methylation of the gene. Hypermethylation of the gene was observed in 77.8% (35/45) of the HSCC tissues, while it was found in only 42.2% (19/45) of the corresponding non-malignant tissues. GRK6 methylation was related to depth of tumor invasion and TNM stage. Upon treatment with 5-aza-2'-deoxycytidine, GRK6 expression was upregulated in FaDu cells, and cell invasion was signinficantly inhibited. Furthermore, the suppression of GRK6 by shRNA transfection enhanced FaDu cells invasion. Our results indicate that the aberrant methylation of GRK6 gene promoter may underlie its downregulation in HSCC, and may play an important role in the metastasis of HSCC.

Lee WI, Ameratunga M, du Plessis J, Gan H
Hypopharyngeal large cell neuroendocrine carcinoma.
BMJ Case Rep. 2015; 2015 [PubMed] Related Publications
Neuroendocrine carcinoma (NEC) of the head and neck is rare. We report a case of a 56-year-old man with a 6-week history of dysphagia, a neck mass and weight loss. He was diagnosed with a hypopharyngeal large cell NEC (LCNEC) with metastases to multiple sites. He received two cycles of cisplatin and etoposide. Subsequent restaging scan revealed progressive disease. The patient declined further chemotherapy and died shortly after. This is the third case of LCNEC of hypopharynx reported in the English literature and the first to progress on platinum-based chemotherapy. Although LCNEC of the head and neck is still classified as an atypical carcinoid, there is increasing evidence it is a distinct clinicohistopathological entity that carries an especially poor prognosis. Currently, there is a paucity of data to guide treatment of this rare malignancy.

Janoray G, Pointreau Y, Garaud P, et al.
Long-term Results of a Multicenter Randomized Phase III Trial of Induction Chemotherapy With Cisplatin, 5-fluorouracil, ± Docetaxel for Larynx Preservation.
J Natl Cancer Inst. 2016; 108(4) [PubMed] Related Publications
BACKGROUND: The purpose of GORTEC 2000-01 was to compare the long-term efficacy and safety of induction chemotherapy with cisplatin (P) and 5-fluorouracil (F) with or without docetaxel (T) for larynx preservation.
METHODS: Operable patients with untreated stage III or IV larynx or hypopharynx invasive squamous cell carcinoma who required total laryngectomy were randomly assigned to three cycles of induction chemotherapy with either TPF or PF, followed by radiation therapy for responders. The primary endpoint was three-year larynx preservation rate. Secondary endpoints included larynx dysfunction-free survival (LDFFS), overall survival (OS), disease-free survival (DFS), loco-regional control rate (LCR), cause of death, and later toxicity rates. Survival and other data were analyzed by Kaplan-Meier methods. All statistical tests were two-sided.
RESULTS: Two hundred thirteen patients were treated with median follow-up of 105 months. The five- and 10-year larynx preservation rates were 74.0% (95% CI = 0.64 to 0.82) vs 58.1% (95% CI = 0.47 to 0.68) and 70.3% (95% CI = 0.58 to 0.8) vs 46.5% (95% CI = 0.31 to 0.63, P = .01) in the TPF vs PF arm, respectively. The five- and 10-year LDFFS rates were 67.2% (95% CI = 0.57 to 0.76) vs 46.5% (95% CI = 0.36 to 0.57) and 63.7% (95% CI = 0.52 to 0.74) vs 37.2% (95% CI = 0.24 to 0.52, P = .001), respectively. OS, DFS, and LCR were not statistically improved in the TPF vs the PF arm. Statistically fewer grade 3-4 late toxicities of the larynx occurred with the TPF regimen compared with the PF arm (9.3% vs 17.1%, G-test, P = .038).
CONCLUSION: Long-term follow-up confirms that induction chemotherapy with TPF increased larynx preservation and larynx dysfunction-free survival. In this larynx preservation approach using induction chemotherapy, TPF should be recommended, followed by radiation therapy.

Subramaniam N, Hiremath B
Leukemoid reaction as a paraneoplastic syndrome in hypopharyngeal squamous cell carcinoma with cutaneous metastasis: an exceedingly rare occurrence.
BMJ Case Rep. 2015; 2015 [PubMed] Related Publications
Head and neck squamous cell carcinoma is considered a locoregional disease, with a distinct chance of metastasis, however, skin is an unusual site. Haematological paraneoplastic syndromes are even rarer, and may be the only presenting feature in these malignancies, producing diagnostic confusion. Cutaneous metastasis, in addition to signifying poor response to treatment and prognosis, can cause diagnostic difficulty if the metastasis is located with an occult primary, and is associated with a higher incidence of multiple synchronous primaries. This article describes a 52-year-old patient with multiple swellings on the left side of the neck and hoarseness of voice. On evaluation, the multiple swellings were found to be cutaneous metastasis from a hypopharyngeal squamous cell carcinoma, with a leukemoid reaction. He opted for palliative radiotherapy and succumbed to his illness within 3 months of presentation. This article discusses the importance of this unusual presentation and diagnostic difficulties associated with it.

Palao-Suay R, Rodrigáñez L, Aguilar MR, et al.
Mitochondrially Targeted Nanoparticles Based on α-TOS for the Selective Cancer Treatment.
Macromol Biosci. 2016; 16(3):395-411 [PubMed] Related Publications
The aim of this work is the preparation of an active nanovehicle for the effective administration of α-tocopheryl succinate (α-TOS). α-TOS is loaded in the core of nanoparticles (NPs) based on amphiphilic pseudo-block copolymers of N-vinyl pyrrolidone and a methacrylic derivative of α-TOS. These well-defined spherical NPs have sizes below 165 nm and high encapsulation efficiencies. In vitro activity of NPs is tested in hypopharynx squamous carcinoma (FaDu) cells and nonmalignant epithelial cells, demonstrating that the presence of additional α-TOS significantly enhances its antiproliferative activity; however, a range of selective concentrations is observed. These NPs induce apoptosis of FaDu cells by activating the mitochondria death pathway (via caspase-9). Both loaded and unloaded NPs act via complex II and produce high levels of reactive oxygen species that trigger apoptosis. Additionally, these NPs effectively suppress the vascular endothelial growth factor (VEGF) expression of human umbilical vein endothelial cells (HUVECs). These results open the possibility to use this promising nanoformulation as an α-TOS delivery system for the effective cancer treatment, effectively resolving the current limitations of free α-TOS administration.

Katsoulakis E, Riaz N, Hu M, et al.
Hypopharyngeal squamous cell carcinoma: Three-dimensional or Intensity-modulated radiotherapy? A single institution's experience.
Laryngoscope. 2016; 126(3):620-6 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
OBJECTIVES/HYPOTHESIS: Compare outcomes of hypopharyngeal carcinoma that received conventional radiotherapy versus intensity-modulated radiotherapy (IMRT).
STUDY DESIGN: Retrospective single-institution trial.
METHODS: Between April 1990 and May 2011, 100 patients with hypopharyngeal cancer underwent curative radiotherapy (RT) at our institution: 50 with IMRT and 50 with conventional RT. The median age was 63 years. There were 12 T1, 22 T2, 37 T3, and 28 T4 patients. The majority of patients (82%) had nodal disease: 54% N2 and 8% N3. The majority of patients (83%) received chemotherapy. Of the patients who received chemotherapy, 84% received a platinum-based regimen. The median RT dose was 7,000 cGy. The majority of patients (62%) had prophylactic percutaneous endoscopic gastrostomy tube placement. Toxicities were reviewed. Local control (LC), locoregional control (LRC), freedom from distant metastasis (FFM) rates, functional larynx preservation (LP), laryngectomy-free survival (LFS), and overall-survival (OS) curves were generated using the Kaplan-Meier method. The log-rank test was used to test prognostic variables.
RESULTS: With a median follow up of 48.4 months, the 3/5-year LC, LRC, FFM, LP, LFS and OS rates were 74%/69%, 77%/74%, 70%/66%, 51%/29%, 49.6%/31.8%, and 49%/34%, respectively. The median OS was 2.9 years. The 3-year LC rate for IMRT was 77% versus 81% for conventional RT (P = .91); 3-year LRC for IMRT was 85% versus 76% for conventional RT (P = .32). There was no increased local failure with IMRT. There was no difference in the rate of stricture with IMRT (32%) versus conventional RT (25.3%) (P = .86).
CONCLUSIONS: IMRT achieved comparable LC and LRC rates to conventional RT.
LEVEL OF EVIDENCE: 4 Laryngoscope, 126:620-626, 2016.

Lim SH, Lee SJ, Ahn MJ, et al.
Different clinical outcomes between locally advanced hypopharyngeal and oropharyngeal cancer treated with definitive concurrent chemoradiotherapy: implication for subgroup selection for induction chemotherapy.
Jpn J Clin Oncol. 2016; 46(1):40-5 [PubMed] Related Publications
OBJECTIVE: The purpose of this study is to compare the long-term clinical outcome of hypopharynx cancer and oropharynx cancer treated with concurrent chemoradiotherapy.
METHODS: A total of 213 patients with locally advanced hypopharyngeal squamous cell carcinoma (n = 79) or oropharygeal squamous cell carcinoma (n = 134) were included. All patients were treated with upfront concurrent chemoradiotherapy between 1995 and 2012.
RESULTS: The median overall survival and progression-free survival differed significantly between the two groups (P < 0.05). Overall survival and progression-free survival rates at 3 years were 52% and 42% for hypopharynx cancer, and 75% and 72% for oropharynx cancer, respectively. There was no significant difference in the overall incidence of distant metastases but more locoregional recurrences occurred in patients with hypopharynx cancer compared with those with oropharynx cancer with a statistical significance (P < 0.001).
CONCLUSIONS: Patients diagnosed with locally advanced hypopharyngeal had relatively poor survival after upfront concurrent chemoradiotherapy. More intensive treatment such as induction chemotherapy before concurrent chemoradiotherapy might be needed to improve survival outcome in this subgroup of patients.

Arslanoğlu S, Eren E, Özkul Y, et al.
Management of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma.
Eur Arch Otorhinolaryngol. 2016; 273(2):511-5 [PubMed] Related Publications
The objective of this study was to determine the incidence of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma; and the association between clinicopathological parameters and thyroid gland invasion. Medical records of 75 patients with laryngeal and hypopharyngeal squamous cell carcinoma who underwent total laryngectomy with thyroidectomy were reviewed, retrospectively. Preoperative computed tomography scans, clinical and operative findings, and histopathological data of the specimens were evaluated. There were 73 male and two female patients with an age range of 41-88 years (mean 60.4 years). Hemithyroidectomy was performed in 62 (82.7 %) and total thyroidectomy was performed in 13 patients (17.3 %). Four patients had histopathologically proven thyroid gland invasion (5.3 %). In three patients, thyroid gland involvement was by means of direct invasion. Thyroid gland invasion was significantly correlated with thyroid cartilage invasion. Therefore, prophylactic thyroidectomy should not be a part of the treatment policy for these tumors.

Rzepakowska A, Osuch-Wójcikiewicz E, Bruzgielewicz A, Niemczyk K
Non-epithelial neoplasms of the larynx and hypopharynx - 12 - years of experience.
Otolaryngol Pol. 2015; 69(5):9-15 [PubMed] Related Publications
OBJECTIVE: The non-epithelial neoplasms of larynx and hypopharynx are of rare incidence but may originate from various histological tissues. These effect in the difficulty of final diagnosis and often delay the proper treatment.
MATERIAL AND METHODS: There was performed retrospective analysis of patients with histopathologicaly confirmed non-epithelial neoplasms of larynx or hypopharynx between 2001 and 2013, that included the evaluation of epidemiology, diagnostic methods and treatment.
RESULTS: Non-epithelial neoplasms of larynx and hypopharynx were established in 18 patients (9 women, 9 men), mean age - 60,3 years. The malignant neoplasms were diagnosed in 10 patients and benign - in 8. The soft tissue neoplasms were the most common - 8 patients. There were also 4 lymphomas, 4 chondrosarcomas, 1 paraganglioma and 1 malignant melanoma. Tumors manifested clinically as covered by unchanged mucosa. Characteristic features were observed on computed tomography for certain cases of these neoplasms. The results of the tumor biopsy were in most of the cases not diagnostic. Intralaryngeal microsurgery was applied in benign neoplasms, chemiotherapy - for lymphomas and total laryngectomy for chondrosarcomas and malignant melanoma.

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