Incidence and survival in patients with pharyngeal cancer in northern Finland

A population-based survey was conducted in northern Finland in order to study the incidence rate and survival in patients with pharyngeal cancer diagnosed between 1986 to 1996. A total of 95 new patients with hypopharyngeal, oropharyngeal or nasopharyngeal cancers were identified. The overall age-adjusted incidence rates (per 100,000 years) were 1.28 in men and 0.60 in women, giving an overall incidence rate of 0.89. Most of the tumours were diagnosed at stage IV, and the median disease-specific survival times were 27.6 months for the patients with oropharyngeal cancer, 13.5 months for nasopharyngeal cancer and 17.7 for hypopharyngeal cancer. The most important factors that were associated with a poor prognosis were stage IV in oropharyngeal [Hazard ratio (HR) 3.68, 95% confidence interval (CI) 0.97-13.92] and hypopharyngeal cancer (HR 3.99, CI 1.51-10.67) and age over 65 years in nasopharyngeal cancer (HR 9.28, CI 1.79-47.99).     

‘When will I see you again?’ Using local recurrence data to develop a regimen for routine surveillance in post‐treatment head and neck cancer patients

Objective: To develop an evidence‐based regimen for routine surveillance of post‐treatment head and neck cancer patients. Design: Review of 10 years of prospectively collected patient data. Main outcome measures: Time of first presentation of ‘new cancer event’ (either first recurrence or second primary tumour). We did not evaluate whether or not the detected new cancer events were curable. Results: Data from patients with primary squamous cell carcinoma of the larynx, oropharynx and hypopharynx were analysed. A total of 676 previously undiagnosed squamous cell carcinomas were recorded in these regions. In these patients there were 105 recurrences and 20 second primary cancers were recorded; 95^th percentile of “time to a new cancer event” was calculated in years. These were for larynx 4.7 years, oropharynx 2.7 years, hypopharynx 2.3 years. The time to new cancer event was similar for early and late laryngeal cancers. Only 36 (47%) of the hypopharyngeal cancers were treated with curative intent and of these 36% had a previously undiagnosed cancer event. Conclusion: Local data and published evidence support a follow‐up duration of 7 years for laryngeal primaries and 3 years for both oropharyngeal and hypopharyngeal primaries. Late stage oropharyngeal cancers may require longer follow up than early cancers. Patients who continue to smoke may need longer follow up. A change in local follow‐up protocol to this regimen would save 10 patient slots every week with no detriment to patient care. Clin. Otolaryngol. 2009, 34 , 546–551.     

Manometric abnormality in dysphagic patients after medullary cerebrovascular accidents

We investigated the pharyngeal swallowing function using videomanofluorometry (VMF) in patients after medullary cerebrovascular accidents. Upper esophageal sphincter pressure, which should drop when a bolus arrives at the hypopharynx, increased at the same time as the elevation of oropharyngeal and hypopharyngeal pressures. A reduction of oropharyngeal and hypopharyngeal swallowing pressures was also observed. Our results suggest that a misprogrammed excitatory output from the central pattern generators of the brain stem would cause an abnormal pressure-traveling pattern of pharyngeal swallowing. VMF was useful to assess the pharyngeal swallowing function and to determine the indications for cricopharyngeal myotomy for patients after medullary cerebrovascular accidents.     

Pepsin and Laryngeal and Hypopharyngeal Carcinomas

Laryngeal and hypopharyngeal carcinomas are common malignant tumors of the head and neck, and the incidence of both is increasing. Laryngopharyngeal reflux refers to the retrograde flow of gastric contents into the larynx, oropharynx, and/or nasopharynx. It remains controversial whether laryngopharyngeal reflux is a risk factor for laryngeal and hypopharyngeal cancers. The refluxing substances mainly include hydrochloric acid, pepsin, and occasionally bile acids and bile salts, as well as bacteria that colonize the gastrointestinal tract. Loss of epithelium in the mucous membrane of the larynx and hypopharynx is thought to be caused by pepsin. Here, we review the relationships between laryngopharyngeal reflux and both laryngeal and hypopharyngeal carcinomas, as well as the significance of pepsin, methods of clinical detection, and the mechanism of carcinogenesis.     

喉咽癌内镜检查时显露方法及其对病变侵犯范围的评价

目的探讨喉镜检查时喉咽部位的显露方法,提高喉镜对喉咽癌局部侵犯范围判断的准确性。方法 113例喉咽癌患者术前行喉镜检查,喉镜检查时喉咽部的显露采用颈前皮肤牵拉法和吹气球法,观察这两种方法的联合应用对喉咽癌原发病灶和局部侵犯范围的判断情况。结果113例喉咽癌患者中,平静呼吸时仅有33例(29.2%)能够清楚显示喉咽部的具体情况,使用颈前皮肤牵拉法和吹气球法后,有106例(93.8%)能够清楚显示喉咽部的情况,明显优于平静状态下对病变的显露和判断(χ2=99.591,P<0.001)。这两种方法的联合应用对喉咽后壁和环后区是否受侵犯的判断具有明显的优势。结论喉镜检查是喉咽癌术前诊断的一种重要方法,通过使用颈前皮肤牵拉法和吹气球法能够将喉咽后壁和环后区充分分离,使喉咽各壁显露出来,从而明显提高喉咽癌术前分期的准确性。     

Inducible nitric oxide synthase expression in pharyngeal squamous cell carcinoma: relation to p53 expression,clinicopathological data,and survival

OBJECTIVE: To investigate the expression of inducible nitric oxide synthase (iNOS) in oropharyngeal and hypopharyngeal squamous cell carcinoma (SCC) and its relation to p53 expression, histologic differentiation, clinical data, and prognosis. STUDY DESIGN: A retrospective survey. METHODS: Primary tumors for analyses were obtained from 118 patients diagnosed with SCC of the oropharynx or hypopharynx between 1975 and 1998 in eastern Finland. Immunohistochemical analysis was used to evaluate the expression of iNOS and p53. The expression pattern of iNOS was related to p53 expression, clinical data, and survival. RESULTS: High iNOS score was associated significantly with high nuclear p53 expression index (P = .006) and positive cytoplasmic p53 expression (P = .025). The score for iNOS expression was significantly lower in the largest (T4) tumors (P = .043). No association was seen between iNOS score and N or M class, tumor stage, or histologic differentiation. The score for iNOS expression was not related to overall survival. CONCLUSIONS: The expressions of iNOS and p53 seem to be inter-related in pharyngeal SCC, although the causality remains to be clarified. The expression of iNOS shows no prognostic value in pharyngeal SCC.     

Three-year results of combined modality therapy in locally advanced, resectable squamous cell carcinoma of the head and neck

Results of a combined therapy, consisting of preoperative chemotherapy, radical resection and postoperative irradiation, of 51 locally advanced, previously untreated, resectable squamous cancers of the head and neck are reported. The overall response rate to chemotherapy was 58.5% (with 33% complete remissions) and higher in carcinomas of the oral cavity and hypopharynx than of the supraglottis and oropharynx. Three year survival was 53% for the entire group, 75% for hypopharyngeal, 58% for oral, 50% for supraglottic and 32% for oropharyngeal lesions, in responders to chemotherapy statistically significant higher than in non responders and only 18% in the fifteen patients who developed recurrences.     

口咽部鳞状细胞癌与性行为和人乳头状瘤病毒感染

高危型人乳头状瘤病毒感染(high risk human papillomavirus, HR HPV)是头颈部鳞状细胞癌发生的一个重要相关因素,特别是原发口咽部、缺少烟酒等危险因素的患者。口咽肿瘤中确认发现HR HPV,以及流行病学病例对照研究明确HR HPV与口咽癌发病风险的关系,已阐明了二者的联系。重点论述口咽癌患者与非口咽癌患者在口腔、喉腔和下咽部位的比较及性行为方式的影响。明确头颈肿瘤的性行为危险因素对未来肿瘤预防是必不可少的,同时以利于理解现有的HPV疫苗对未来头颈肿瘤预防的潜在作用。同时还扩展到性行为作为口咽癌发生的一个危险因素以及其作为HPV暴露标记的作用,强调HR HPV是通过性行为传播到上呼吸消化道,增加HPV相关的口咽癌的发病风险。     

Value of upper gastrointestinal endoscopic examination of head and neck cancer patients

Between January 1995 and March 1999, we performed the upper gastrointestinal endoscopic examinations on 287 patients with head and neck cancers and detected 23 cases (8%) of esophageal cancer and 8 cases (2.8%) of gastric cancer, showing how frequently esophageal cancer occurs in head and neck cancer. The esophageal cancer involved the oral cavity in 8 cases (9.5%), the oropharynx in 3 cases (8.6%), the hypopharynx in 10 cases (19.6%), and the larynx in 2 cases (2%). Esophageal cancer occurred most frequently in hypopharyngeal cancer, particularly the pyriform sinus type and the postcricoid type. We conclude that upper gastrointestinal endoscopic examination, including Lugol staining, is necessary in head and neck cancer patients.     

Intrapharyngeal distribution of gastric acid refluxate

OBJECTIVES/HYPOTHESIS: Determination of intrapharyngeal distribution of gastric acid refluxate is needed to better understand the pathogenesis of reflux-attributed aerodigestive tract disorders. The aims of the study were to determine intrapharyngeal distribution of gastric acid refluxate and to determine whether this distribution can better differentiate patients from control subjects compared with data obtained from a single hypopharyngeal site. METHODS: We prospectively studied 10 healthy volunteers, 12 patients with reflux laryngitis, and 15 patients with vasomotor rhinitis using a concurrent dual pharyngeal/dual esophageal pH recording technique. We determined the hypopharyngeal and oropharyngeal pH profile, including number, duration, and distribution of reflux events irrespective of and in correlation with intraesophageal pH profile using four different pH thresholds. RESULTS: Few drops in pharyngeal pH were found to be true reflux events based on their correlation with esophageal pH events. For the pharyngeal pH threshold criterion of a drop to 4.0 or less, 6 of 12 patients with reflux laryngitis, 5 of 15 patients with vasomotor rhinitis, and 2 of 10 normal control subjects exhibited a total of 25 (range, 1-5) distal pharyngeal acid reflux events. Overall, 34% of these events reached the oropharyngeal pH recording site. Between-group comparison for all levels of pH threshold criteria did not show any significant difference of reflux parameters in the hypopharyngeal or in the oropharyngeal sites among the studied groups. CONCLUSIONS: Reflux of gastric acid into the pharynx may extend to the region of the oropharynx in both patients and control subjects. Overall distribution of acid refluxate to the oropharynx is low but as groups is similar between healthy individuals and patients with reflux laryngitis and those with vasomotor rhinitis. Parameters of oropharyngeal acid reflux such as number and duration do not differentiate patients from control subjects.     

The upper airway and sleep apnoea in the Prader-Willi syndrome

Obesity, short stature, hypotonia and excessive daytime sleepiness are characteristic features of the Prader-Willi syndrome. Excessive daytime sleepiness has been attributed to obstructive sleep apnoea (OSA). To investigate the role of anatomical factors in OSA in the Prader-Willi syndrome, clinical and ENT assessment, radiology of the upper airway and polysomnography including sleep oximetry were done in 14 subjects. Excessive daytime sleepiness was present in eight of 14 subjects as determined by a mean sleep latency to non-rapid eye movement stage I–II of < 5 min and/or self-rating sleepiness score > 9 (Epworth Sleepiness scale). Seven subjects were snorers or mouth breathers and dental abnormalities were present in 11. Sleep apnoea, as determined by a combined apnoea-hypopnoea index of more than 10 respiratory events per hour was present in 12 of 14 subjects. On clinical assessment, the nasopharynx, oropharynx and hypopharynx were small in one subject. No subject had redundant pharyngeal mucosa or an enlarged tongue. However, radiological studies performed in the awake supine posture showed a slight reduction in the cross-sectional area in nine subjects at the oropharyngeal level and in four subjects at the nasopharyngeal level as compared with normal control subjects. Sleep apnoea and minor radiological evidence of narrowing of the upper airway are common in the Prader-Willi syndrome, although clinical otolaryngological examination is often unremarkable. Excessive daytime sleepiness occurs in approximately 50% of all patients with Prader-Willi syndrome. Although obstructive sleep apnoea is one important factor related to sleepiness, an additional central disturbance of sleep mechanisms is present.     

Anatomic correlates of normal and diseased adenoids in children.

In order to better understand the pathogenesis and sequelae of obstructive adenoid hyperplasia in children, the anatomic relationships of the adenoids to the hard and soft palates, oropharynx, and nasopharynx were studied in vivo in 94 children. Direct, intraoperative palatal, nasopharyngeal, and oropharyngeal measurements were performed in 19 children with normal, nondiseased adenoids (controls [C]) and compared to 75 children undergoing adenoidectomy for obstructive adenoid hyperplasia (OAH) (n = 44) or chronic adenoid infection (CAI) (n = 31). As expected, the weight and volume of the adenoids removed were significantly greater in the OAH vs. CAI group (P < .001). Before adenoidectomy, the volume of the nasopharynx was significantly smaller in the OAH group; however, nasopharyngeal volumes after adenoidectomy were quite similar in all three groups and ranged from 5.4 to 6.2 cc. Only the change in the volume of the nasopharynx after adenoidectomy for obstruction was significant (2.5 +/- 1.2 cc, P < .01). Differences in oropharyngeal and palatal dimensions were not associated with longstanding obstruction from adenoid hyperplasia. These data indicate that the nasal obstruction from adenoid hyperplasia is due to an absolute increase in adenoid size rather than a relatively smaller nasopharynx. Differences in palatal and oropharyngeal dimensions usually described and attributed to longstanding nasal obstruction could not be demonstrated in this study.     

Long-term results of a multimodal intensification regimen for previously untreated advanced resectable squamous cell cancer of the oral cavity, oropharynx, or hypopharynx

BACKGROUND: Long-term disease control of an intensified treatment regimen for previously untreated stage III and IV resectable oral cavity, oropharyngeal, or hypopharyngeal squamous cell carcinoma was analyzed. METHODS: Forty-three patients with previously untreated, advanced stage, resectable squamous carcinomas of the oral cavity, oropharynx, or hypopharynx were enrolled in a prospective phase II institutional clinical trial at a tertiary care National Cancer Institute-designated comprehensive cancer center. It includes preoperative accelerated hyperfractionated radiotherapy with concurrent cisplatin followed immediately by surgery and intraoperative radiotherapy, and completed with early postoperative weekly paclitaxel, two additional cisplatin cycles, and concurrent once-daily radiotherapy beginning on day 28 after surgery. RESULTS: Forty-three patients enrolled in the study. Protocol compliance was 53%. The range of time at risk was 10.4 to 56.23 months (median, 45 months). The locoregional (93%) and systemic (91%) disease control rates were excellent. Overall long-term survival was 79%. CONCLUSIONS: An intensive treatment regimen that improves compliance and long-term disease control is clearly feasible for this patient population.     

Variability of genetic alterations in different sites of head and neck cancer

OBJECTIVE: Tumors arising from different sites of the head and neck area have different clinical behavior. However, most of the studies on genetic alterations in head and neck squamous cell carcinomas do not make a distinction between the sites within this area. The objective of this study is to compare the genetic alterations in three different sites of the head and neck (larynx, oropharynx, and hypopharynx). STUDY DESIGN: Prospective study. METHODS: Thirty-eight laryngeal, 29 oropharyngeal, and 37 hypopharyngeal carcinomas were studied. DNA from tumor and healthy tissue was evaluated for amplification of the oncogenes at 11q13 region (CCND1, FGF3, FGF4 and EMS1) and of the oncogenes MYC and ERBB1; for integration of the human papillomavirus (HPV) types 6b and 16; for loss of heterozygosity (LOH) at p53 and NAT2; and for the cellular DNA content. RESULTS: FGF3 and FGF4 showed a significantly higher frequency of amplification in hypopharyngeal tumors (P =.006 and P =.0002, respectively). CCND1 amplification had a nearly statistically significant (P =.072) higher frequency of amplification in hypopharyngeal tumors. Aneuploid tumors were found in a significantly lower proportion in the larynx (P =.03) compared with the other sites. For the other genetic alterations, no significant differences among the three sites were found. CONCLUSIONS: These results suggest that cancers originating from different sites in the head and neck may have different tumor biology. Therefore, they should be considered as different entities.     

CIP2A在下咽癌中的表达及临床意义

目的 探讨下咽癌组织中蛋白磷酸酶2A的癌性抑制因子(CIP2A)的表达与患者临床病理特征和预后的关系。方法 于川北医学院附属医院病理科收集2016年1月至2020年12月下咽癌组织标本共58例,其中配对癌旁组织标本20例,同时选取30例正常下咽组织纳入分析。结果 免疫组化SP显示,CIP2A在下咽癌组织中的表达水平显著高于在癌旁及正常下咽组织中的表达水平(P<0.001)。CIP2A的表达与患者是否饮酒、病理分化程度、临床分期、是否有淋巴结转移有明显关系(P<0.05),而与性别、年龄、是否吸烟、临床分型无明显关系。单因素Log-rank检验分析显示患者年龄、临床分期、CIP2A表达与患者预后相关(P<0.05)。进一步Cox风险比例回归模型分析发现CIP2A表达是影响下咽癌预后的独立危险因素。结论 蛋白磷酸酶2A的癌性抑制因子CIP2A在下咽癌组织中异常表达提示其可能参与了肿瘤的发生发展,CIP2A高表达的下咽癌患者预后较差,故CIP2A有望成为下咽癌患者诊断、治疗与预后的分子标志物之一。     

Predictive factors for diagnosis of advanced-stage squamous cell carcinoma of the head and neck

OBJECTIVE: To identify the predictive factors (with emphasis on diagnostic delay) associated with the diagnosis of an advanced-clinical stage head and neck cancer. DESIGN: Cross-sectional study of patients with head and neck cancer originally recruited for a case-control study. SETTING: Three referral oncological centers in metropolitan areas in southern Brazil: S?o Paulo, Curitiba, and Goiania. PATIENTS: The study population comprised 679 patients recently diagnosed as having a previously untreated head and neck squamous cell carcinoma. MAIN OUTCOME MEASURE: Diagnosis of advanced disease (clinical stage III-IV) head and neck cancer. RESULTS: Patients with laryngeal and hypopharyngeal cancers were more likely to be diagnosed as having advanced disease than those with lip, oral, and oropharyngeal cancers (88.0% vs 74.6%) (P<.001). Patient delay was inversely associated with clinical stage at diagnosis in patients with the same cancers, while professional delay was directly associated with a higher risk of advanced clinical stage at diagnosis (P =.001 and P =.006, respectively). In the analysis of laryngeal and hypopharyngeal cancer, both patient and professional delays were associated with advanced disease, with patient delay being a stronger predictive factor than professional delay. CONCLUSIONS: Clinical stage at diagnosis was associated with sociodemographic characteristics, patient delay, and professional delay. Our results indicate that continued educational programs for the population and health care professionals regarding the identification of early symptoms of head and neck cancers are warranted.     

Malignant neoplasms of the oral cavity and oropharynx treated in Brazil: what do hospital cancer records reveal?

IntroductionHead and neck cancer has an impact on the global burden of diseases, representing an important cause of morbidity and mortality in Brazil, as well as worldwide.ObjectiveTo learn and describe the clinical, epidemiological and care configuration provided to patients with cancer of the oral cavity and oropharynx recorded in Brazil, diagnosed from 2007 to 2016.MethodsThis is a cross-sectional study, carried out using secondary hospital-based data, using the indirect documentation technique.ResultsThere were 52,799 hospital records of oral cavity cancer and 34,516 cases of oropharyngeal cancer in the assessed period. There was a predominance of male patients, aged 50–59 years, mostly Caucasians, and with a low level of schooling. Throughout the period there was a significant reduction in the positive history of alcohol and tobacco consumption, except for alcoholic beverages in oral cavity cancer. Most patients were diagnosed at an advanced stage of the disease (III or IV). Most patients with oral cavity cancer had no evidence of the disease on follow-up, while most patients with oropharyngeal cancer died. The first most frequent treatment offered to patients with oral cavity cancer was surgery, while for patients with oropharyngeal cancer it chemoradiotherapy predominated.ConclusionDespite the fact that, in general, there was a reduction in the records of patient alcohol and tobacco consumption, the increase in the number of medical consultations, the predominantly late diagnosis and the patients’ low level of schooling indicate the need for health education, primary prevention and early diagnosis of cancer of the oral cavity and oropharynx.     

Carcinoma of the posterior wall of the hypopharynx: surgical treatment with larynx preservation

IntroductionPosterior pharyngeal wall is the most rare subsite for hypopharyngeal carcinomas. Because of its rarity, there are few studies published in the literature specifically concerning posterior pharyngeal wall carcinoma.ObjectivesTo report our functional results in patients with the carcinoma of the posterior wall of the hypopharynx after surgical treatment by resection via a lateral or infrahyoid pharyngotomy approach, with the preservation of the larynx and reconstruction with a radial forearm free flap.MethodsThe study included 10 patients who underwent surgery for a carcinoma of the posterior wall of the hypopharynx over a 6 year period. The associated postoperative morbidity was investigated and functional results were analyzed.ResultsNine patients had T3 lesions and one patient had a T2 lesion. The preferred approach to access the hypopharynx was a lateral pharyngotomy in 5 patients and lateral pharyngotomy combined with infrahyoid pharyngotomy in 5 patients with superior extension to oropharynx. The pharyngeal defects were reconstructed successfully with radial forearm free flaps. Four patients received adjuvant radiotherapy only, and 4 patients with N2b and N2c neck diseases received adjuvant chemoradiotherapy. The mean duration of hospitalization was 15.6 days (range, 10–21 days). All patients achieved oral intake in a median time of 74 days (range, 15–180). Decannulation was achieved in all patients and the median time for decannulation was 90 (range, 21–300 days). The mean followup duration was 38.3 months (range, 10–71 months) and 8 patients survived. One patient died due to regional recurrence in the retropharyngeal lymph nodes and 1 patient died due to systemic metastasis.ConclusionPrimary surgery is still a very effective treatment modality for the carcinoma of the posterior wall of the hypopharynx and does not permanently compromise the swallowing and laryngeal functions if pharyngeal reconstruction is performed with a free flap.     

Evaluation of the usefulness of upper gastrointestinal endoscopy and the ValsamouthⓇ by an otolaryngologist in patients with Hypopharyngeal cancer

ObjectiveThe aim of this retrospective study is to evaluate the usefulness of upper gastrointestinal endoscopy and the Valsamouth^? by an otolaryngologist in patients with hypopharyngeal cancer to assess the risk.MethodsThe study group comprised 41 patients with untreated hypopharyngeal cancer that was precisely diagnosed by an otolaryngologist using upper gastrointestinal endoscopy and the Valsamouth^? at our hospital from January 2016 to December 2017. With upper gastrointestinal endoscopy and the Valsamouth^?, the oral cavity, oropharynx, larynx, hypopharynx, and esophagus were observed in this order. Narrow-band imaging, and subsequently, white-light observation were performed. At the hypopharynx, vocalization, and subsequently, the Valsalva maneuver were performed. After observing the esophagus, Lugol chromoendoscopy of the esophagus was performed.ResultsThe mean age of the 38 men and 3 women included in the study was 69.7 ± 10.0 years (range, 51–94 years). As for the T category of hypopharyngeal cancer, T1 cancer was observed in 9 patients, T2 cancer in 14, T3 cancer in 11, and T4 cancer in 7. With vocalization, the grade of visualization in the hypopharynx was 1 in 30 patients (73.2%), 2 in 11 patients (26.8%), and 3 or more in 0 patients (0.0%). With the Valsalva maneuver, the grade of visualization in the hypopharynx was 1 in 1 patient (2.4%), 2 in 15 patients (36.6%), 3 in 8 patients (19.5%), 4 in 11 patients (26.8%), and 5 in 6 patients (14.6%). The grade of visualization in the hypopharynx on average was 1.27 after vocalization and 3.15 after the Valsalva maneuver (p < 0.001). With vocalization, the percentage of patients in whom the entire image of hypopharyngeal cancer could be observed was 0.0% for grade 1 and 18.2% for grade 2. With the Valsalva maneuver, the percentage of patients in whom the entire image of hypopharyngeal cancer could be observed was 0.0% for grade 1, 40.0% for grade 2, 50.0% for grade 3, 86.1% for grade 4, and 100% for grade 5. Synchronous esophageal cancers were detected in 17.1% (7/41) of the patients. The grade of Lugol-voiding lesions was A in 5.6%, B in 52.8%, and C in 41.7%.ConclusionThe examination with upper gastrointestinal endoscopy and the Valsamouth^? by an otolaryngologist is feasible in patients with hypopharyngeal cancer. This procedure can detect synchronous esophageal cancer, allowing the risk of metachronous cancer in the head and neck or the esophagus to be recognized after the treatment.