May Nutritional Status Positively Affect Disease Progression and Prognosis in Patients with Esophageal and Pharyngeal Cancers? A Scoping Review of the Current Clinical Studies.

BACKGROUND: Malnutrition in esophageal and pharyngeal cancer patients constitutes a common and serious concern, which significantly reduces patients' prognoses. Cancers of the esophagus and the pharynx can considerably impair feeding in patients, resulting in severe undernutrition. This is a scoping review that intends to critically analyze the most well-designed clinical studies investigating the potential beneficial impact of diverse nutritional assessment tools on the prognosis of patients with esophageal and pharyngeal cancers. METHODS: The most accurate and remarkable scientific databases were comprehensively explored utilizing relative keywords to detect clinical studies that investigate whether nutritional status may affect disease prognosis. RESULTS: Several assessment tools have evaluated and highlighted the potential beneficial impact of nutritional status on disease progression and patients' prognosis in both esophageal and pharyngeal cancers. Regarding esophageal cancer, CONUT, PNI, PG-SGA, and NRS-2002 are more commonly used, while albumin is also frequently evaluated. Regarding pharyngeal cancers, fewer studies are currently available. PNI has been evaluated, and its significance as a factor for shorter survival' times has been highlighted. The Comprehensive Nutritional Index has also been evaluated with positive results, as well as NRS 2002, GPS, and body-weight status. However, there is currently a lack of studies with an adequate number of women with cancer. An international literature gap was identified concerning follow-up studies with adequate methodology. CONCLUSIONS: Nutritional status may significantly affect disease progression and patients' survival, highlighting the significance of a great nutritional status in individuals with esophageal and pharyngeal cancers. Further large-scale and well-designed prospective surveys should be performed to verify the potential beneficial effects of adequate nourishment in people suffering from cancer of the esophagus and pharynx.

ALDH2 polymorphism, alcohol intake and the attributable burden of cancer in East Asia: systematic review, meta-analysis, and modeling study.

PURPOSE: To estimate the burden of alcohol-attributable cancer in East Asian populations accounting for aldehyde dehydrogenase-2 (ALDH2) genotype-specific cancer risk and alcohol exposure. METHODS: We conducted a systematic review and meta-analysis of eight databases on cancer risk to derive alcohol dose-response curves by ALDH2 genotype. A simulation-based approach using the Global Burden of Disease (GBD) modeling framework was applied to estimate the population attributable fraction, incidence, and disability-adjusted life-years (DALYs) lost to alcohol-attributable cancer. RESULTS: We included 34 studies (66,655 participants) from China, Japan, and South Korea in the meta-analysis. Alcohol dose-response curves for liver, esophageal, and oral cavity/pharynx cancer showed an increased risk for people with the inactivated ALDH2 genetic polymorphism, resulting in a higher burden of alcohol-attributable cancer compared to GBD estimates. Our methods estimated annual incidence of cancer of 230,177 cases, an underestimate of 69,596 cases compared to GBD estimates. Similarly, total DALYs lost annually were underestimated by 1.20 million. CONCLUSIONS: The burden of liver, esophageal, and oral cavity/pharynx cancer attributable to alcohol is underestimated in populations with the ALDH2 genetic polymorphism when compared to current estimates.

Factors Related to Human Papillomavirus Positivity among Oral Cavity and Pharynx Cancers from Surveillance, Epidemiology and End Results (SEER) Program Data.

BACKGROUND: As human papillomavirus positive (HPV+) oral cavity and pharynx cancer (OCPC) incidence increases significantly, our objective was to determine whether selected sociodemographic and clinical factors were associated with HPV+ OCPCs overall and by oropharyngeal and non-oropharyngeal sites. METHODS: Surveillance, Epidemiology and End Results (SEER) Program data were used in this study. Specifically, univariate and logistic regression models were used to examine the relationships between HPV+ and HPV- OCPC cases and age, sex, race, ethnicity, marital status, factors of neighborhood socioeconomic status (i.e., nSES/Yost index) and rurality/urbanity, first malignancy status, histology, reporting source, stage at diagnosis, and OCPC anatomic site. The same approach was used to identify risk factors for HPV positivity for oropharyngeal and non-oropharyngeal OCPCs separately. RESULTS: In all OCPCs, cases that were male, <80 years old, lived in the four highest nSES categories, diagnosed with a non-"gum and other mouth" OCPC (ref = hypopharynx), not locally staged at diagnosis, and a first malignancy had higher odds of being HPV+. Cases that were American Indian/Alaska Native and Asian or Pacific Islander (ref = White), Spanish-Hispanic-Latino ethnicity, non-married/partnered, and not reported by a hospital/clinic had lower odds of being HPV+. Associations were maintained in oropharyngeal OCPCs and only age and race remained significant for non-oropharyngeal OCPCs. CONCLUSIONS: Sociodemographic and clinical differences in HPV+ and HPV- OCPC, overall and for (non)oropharyngeal, cases exist. IMPACT: Identification of OCPC and (non)oropharyngeal risk factors for HPV positivity may assist in discovering high-risk groups that should receive enhanced public health efforts to reduce the U.S. OCPC burden.

Swallowing functional outcomes and nutritional status in head and neck cancer radiotherapy: longitudinal study.

OBJECTIVE: To explore the relationships between swallowing functional outcomes and nutritional status in patients with head and neck cancer undergoing radiotherapy (RT). METHODS: This longitudinal study included 122 patients. Data were collected at three time points: baseline (T1), the third week of RT (T2) and the completion of RT (T3). The Common Terminology Criteria for Adverse Events was used to assess the symptom of dysphagia and other toxicities; the MD Anderson Dysphagia Inventory (MDADI) was used to assess the patient-perceived swallowing functional outcomes; the nutritional status was evaluated by the weight ratio and the Patient-Generated Subjective Global Assessment (PG-SGA). The generalised estimating equation (GEE) was used to measure the correlation of MDADI with the weight ratio or PG-SGA and also to analyse the influential factors of swallowing functional outcomes. RESULTS: The participants' acute dysphagia rates were 5.7% at T1, 69.7% at T2 and 77.9% at T3. The swallowing functional outcomes worsen over RT (p<0.001) and were associated with weight ratio (ß=0.032, p=0.008) and PG-SGA (ß=-0.115, p<0.001). GEE models showed that patients with cancer of the pharynx region, advanced stage, chemoradiotherapy and high RT dose perceived worse swallowing functional outcomes. Oral mucositis, pharynx mucositis and salivary gland inflammation were positively correlated with swallowing functional outcomes, and the pharynx mucositis presented the highest absolute value of ß. CONCLUSION: The swallowing functional outcomes were negatively correlated with nutritional status. Healthcare professionals should identify early on the population at higher risk and focus on multiple toxicities, especially the management of pharynx mucositis, to improve nutritional status.

Safe Use of Nivolumab in a Patient with Epipharyngeal Carcinoma and Preexisting Ulcerative Colitis: A Histologically Proven Case Report.

Nivolumab, an antibody against human programmed cell death 1 (PD-1), enhances pre-existing immune responses and has antitumor activity. However, it may also cause undesirable immune-related adverse events (irAEs), such as anti-PD-1-related colitis. In addition, Nivolumab can worsen pre-existing autoimmune diseases. Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Its exact cause is unknown, but it may involve the dysregulation of the mucosal immune response. Thus, it is of great interest whether nivolumab can affect UC activity. This is the first report of a patient with epipharyngeal carcinoma and ulcerative colitis who was confirmed to have been safely treated with nivolumab based on autopsy findings.

Synergistic effect of cisplatin chemotherapy combined with fractionated radiotherapy regimen in HPV-positive and HPV-negative experimental pharyngeal squamous cell carcinoma.

HPV infection renders oropharyngeal squamous cell carcinomas more radiosensitive, which results in a favorable prognosis for HPV-positive patients treated with radiation alone or with concurrent platinum-based chemotherapy. The degree of radiosensitivity in fractionated regimens has not yet been fully explored; therefore, in this study, the radiosensitivity of HPV-negative tumors (FaDu) was compared to that of HPV-positive tumors (2A3) subjected to concurrent cisplatin chemotherapy and fractionated versus isoeffective single-dose tumor irradiation in immunodeficient mice. HPV-positive tumors were approximately 5 times more radiosensitive than HPV-negative tumors, irrespective of the irradiation regimen. In both tumor models, concurrent cisplatin chemotherapy and the fractionated regimen induced significant tumor radiosensitization, with a 3- to 4-fold increase in the tumor growth delay compared to that of single-dose irradiation. Furthermore, the degree of radiosensitization induced by cisplatin chemotherapy concurrent with the fractionated irradiation regimen was much higher in HPV-positive tumors, where a synergistic antitumor effect was observed. Specifically, after combined therapy, a 26% higher survival rate was observed in mice with HPV-positive tumors than in mice with HPV-negative tumors. These data suggest that HPV-positive tumors are more radiosensitive to fractionated regimen than to single-dose irradiation with concurrent cisplatin chemotherapy acting synergistically to irradiation.

A Huge Oropharyngeal Pyogenic Granuloma in a Patient Presenting with Dysphagia.

A 39-year-old woman experienced dyspnea and progressive dysphagia for 1 year. Dysphagia appeared for solid foods at the beginning but advanced for liquids. She described 17 kg weight loss in the past 6 months and her current weight was 38 kg [body mass index (BMI) 16 kg/m2]. Dyspnea presented with effort and lying was included after 1 month. There was no disease or surgery except chronic hepatitis C in her medical history. Physical examination revealed hyponasal speech and a mass beside the tongue base. A smoothly surfaced 4 × 3-cm vascular mass in oropharynx was determined in endoscopic examination. The mass was mobile and occupied 80% of oropharyngeal area. Contrast-enhanced computed tomography revealed hypervascular 4 × 4 × 3 cm pedunculated (8 × 13 mm) mass arising from the right tongue base. The mass and the surrounding mucosa with a thin layer of tongue musculature were excised using cold instrumentation and bipolar cautery. Histologically the mass was reported as pyogenic granuloma (PG). This is the first study to report on oropharyngeal PG causing obvious weight loss in literature.

A huge retropharyngeal lipoma: a rare cause of dysphagia: a case report and literature review.

Dysphagia is commonly seen after a cerebral vascular accident. It is rarely caused by lipomas of the retropharyngeal region which are rare benign mesenchymal neoplasms. We report a case of a 53-year-old man who presented with a history of ptyalism and dysphagia occurring after a brain stroke. Flexible nasal endoscopy revealed a pooling of saliva in both pyriform sinuses. Cervical and neurological examinations were unremarkable. Computed tomography (CT) scan suggested the diagnosis of retropharyngeal lipoma. The mass was resected by trans-cervical approach. The histological examination confirmed the diagnosis of a retropharyngeal lipoma. The postoperative course was unremarkable. Although lipomas in the retropharyngeal space are rare, clinicians should evoke this diagnosis when treating a patient presenting with dysphagia, even if there is a medical history of cerebral vascular accident.

Treatment considerations for cervical and cervicothoracic spondylodiscitis associated with esophageal fistula due to cancer history or accidental injury: a 9-patient case series.

BACKGROUND: The combination of cervical spondylodiscitis and esophageal fistula is rare but life-threatening. Due to both the rarity of these conditions' coincidence and the complexity and heterogeneity of individual cases, there is no optimal treatment or management approach. The aims of this study are to obtain an overview of patients' outcomes and to discuss treatment options. METHOD: This study is a retrospective analysis of patients who presented with cervical spondylodiscitis and associated esophageal fistula between January 2010 and November 2018. We examined reports of 59 patients who suffered from cervical spondylodiscitis and included nine patients (15.25%) who had an esophageal fistula as the underlying cause. We assessed clinical findings, treatment, and outcome. RESULTS: Three of the nine patients were female, and the mean age of the sample was 64.56 years. Six of the patients had a history of esophagopharyngeal cancer and had undergone tumor resection followed by radiotherapy. Two of the remaining patients' fistulas were caused by an iatrogenic injury during cervical spine surgery and a swallowed toothpick; in the final case, the origin remained unclear. Five patients presented with tetraparesis or tetraplegia, and the other four patients were neurologically intact. In seven cases, dorsal instrumentation was initially performed. Three patients secondarily received a ventral approach for debridement, and one received explantation of the ventral implants. Two patients died during the hospital stay, and three were transferred to a palliative care unit. Thus, the spondylodiscitis and esophageal fistula were cured in only four patients. At discharge, two patients were neurologically intact, two others remained in tetraparesis. CONCLUSIONS: Cervical spondylodiscitis in association with an esophageal fistula carries high morbidity and high mortality. Because patients whose infections are not cured have high morbidity, we recommend using interdisciplinary and individual management, including definite surgical treatment of the discitis and fistula, in every case.

A suspected case of drug-induced tubulointerstitial nephritis by pilocarpine hydrochloride.

A 63-year-old man with pharyngeal cancer had been prescribed pilocarpine hydrochloride for xerostomia after concomitant chemoradiotherapy. After 6 months of taking pilocarpine hydrochloride, he was referred to our hospital due to gradually developing renal insufficiency. The patient underwent detailed urinalysis, blood chemistry analysis, immune-serology testing. A renal biopsy was also performed. He was diagnosed with chronic tubulointerstitial nephritis (TIN) caused by lymphocytic infiltration of the interstitium, tubular atrophy, and interstitial fibrotic changes. Infections, autoimmune diseases, and genetic factors were ruled out as causes of TIN; a drug-induced lymphocyte stimulation test confirmed that he had high stimulation index scores for pilocarpine hydrochloride and a normal range stimulation score for other supplements. These results indicated that the TIN could have been induced by pilocarpine hydrochloride. Drug discontinuation partly improved his renal function and tubule marker levels. To our knowledge, this is the first report of TIN following administration of pilocarpine hydrochloride. This finding could contribute to future treatment decisions for patients with TIN and those using pilocarpine hydrochloride.

Parapharyngeal Ganglioneuroma Detected by 18F-FDG PET/CT in a Patient With Hodgkin Lymphoma.

A 38-year-old woman with anterior mediastinal Hodgkin lymphoma underwent F-FDG PET/CT, revealing abnormal uptake at the left retrostyloid parapharyngeal space. After chemotherapy, follow-up PET/CT showed regression of previously avid lesions but not the left retropharyngeal mass. Subsequent MRI revealed findings suggestive of neurogenic tumor. Transoral biopsy revealed ganglioneuroma, which is uncommon in the parapharyngeal space, although usually of benign nature. This case therefore highlights the importance of PET/CT in both initial diagnostic screening for tumor development and posttreatment evaluation of ambiguous lesions.

Cervical osteomyelitis: A new identity of dreaded complication following pharyngeal cancer treatment.

BACKGROUND: Cervical osteomyelitis following the treatment of pharyngeal cancer with laryngectomy and chemoradiotherapy is poorly reported. METHODS: Six cases of cervical osteomyelitis occurring over a 1-year period are described herein. These are reviewed alongside four cases reported previously in the literature. RESULTS: Among the total 10 cases, the average age of the patients was 58.7 years. The period between laryngectomy and the diagnosis of cervical osteomyelitis was on average 3 years and 1 month and the male to female sex ratio was 9:1. Two patients had a history of cervical fistula with an esophageal prosthesis, one had a spontaneous cervical fistula, one had a pharyngeal cutaneous fistula, and one had an esophageal prosthesis without any fistula. At the time of diagnosis, seven had a history of cervical pain (70%) and nine had a neurological deficit (90%). Seven patients (70%) underwent surgery; one (10%) was contraindicated for a general anesthetic and two (20%) died before any intervention. The indication for surgery was a neurological deficit for six patients (60%) and the requirement for lavage and debridement for two patients (20%). The average length of antimicrobial treatment was 12.7 weeks. The outcome was favorable for six patients. Four patients died. CONCLUSIONS: Cervical osteomyelitis is a serious but rarely reported complication following the treatment of pharyngeal cancer with chemoradiotherapy and laryngectomy. Cervical pain was the first sign to appear, sometimes 1year before any other sign. Physicians should be aware of this dreaded complication, which is probably underdiagnosed and is related to an increased mortality rate.

[Glossopharyngeal neuralgia associated with syncopes and secondary to neck carcinoma]. / Neuralgia glosofaringea asociada a sincopes y secundaria a carcinoma de cuello.

TITLE: Neuralgia glosofaringea asociada a sincopes y secundaria a carcinoma de cuello.

Paediatric parapharyngeal ganglioneuroma.

A 17-year-old man initially presented to his primary care physician with throat pain for 1 week and was started on amoxicillin. After four additional days of ongoing pain and difficulty swallowing with decreased oral intake, he presented to the emergency department. Exam showed fullness to the right posterior oropharynx and palpable mass in the right neck without stridor. Initial imaging was soft tissue neck CT with contrast, which showed cystic 8 cm mass in the parapharyngeal space. Patient additionally underwent MRI, which showed an 8.6 cm mass in the right posterior oropharynx with obliteration of the vallecula. Differential diagnosis included abscess; therefore, ear, nose, and throat (ENT) specialist was consulted for possible drainage. Intraoperatively, there was no abscess; alternatively a biopsy was obtained, which was identified by pathology as a ganglioneuroma. Patient was referred to paediatric ENT specialist, underwent extensive resection confirming diagnosis of ganglioneuroma and did well postoperatively.

Electrochemotherapy with cisplatin or bleomycin in head and neck squamous cell carcinoma: Improved effectiveness of cisplatin in HPV-positive tumors.

Human papillomavirus (HPV) is an important etiological factor in head and neck squamous cell carcinomas (SCCs). Standard treatment of HPV-positive tumors with platinum-based radio(chemo)therapy results in a better outcome than in HPV-negative tumors. Electrochemotherapy is becoming an increasingly recognized mode of treatment in different cancers; thus, its use in the management of head and neck SCC is of considerable interest. However, response to electrochemotherapy according to HPV status of the tumors has not been evaluated yet. Thus, our aim was to compare the effect of electrochemotherapy with cisplatin or bleomycin between HPV-negative and HPV-positive human pharyngeal SCC derived cell lines and tumor models. HPV-positive cells and tumors were found to be more sensitive to electrochemotherapy with cisplatin than HPV-negative ones, whereas sensitivity to electrochemotherapy with bleomycin was similar irrespective of the HPV status. The higher sensitivity of HPV-positive cells and tumors to electrochemotherapy with cisplatin is likely due to the higher level and slower repair of DNA damage. In HPV-negative tumors, a higher number of complete responses was recorded after bleomycin-based rather than cisplatin-based electrochemotherapy, while in HPV-positive tumors electrochemotherapy with cisplatin was more effective.

[Retrospective analysis of 188 cases of parapharyngeal space tumors].

Objective:To explore the diagnosis,treatment,surgical approach and prognosis of parapharyngeal space tumors.Method:The clinical data of 188 patients with parapharyngeal space tumor who were treated from January 2007 to December 2016 were analyzed retrospectively.All patients underwent imaging examination before operation.Surgical approach was as follows:transcervical approach applied in 159 cases,endoscopic-assisted transnasal approach in 9 cases,transcervical-transmandibular approach in 8 cases,transcervical-transparotid approach in 8 cases,transoral approach in 7 cases,and infratemporal fossa approach in 4 case.Result:Of the 188 cases,the tumor was benign in nature in 168 cases(89%)and malignant in 20 cases(11%).Complications occurred in 28(15%)patients,with the most common symptom being hoarseness.168 cases of benign tumors were followed up for 10 months to 10 years,and 3 cases were lost and 4 cases had recurrence.All cases underwent re-operation.Patients with malignant tumors received combined treatment after surgery,and 3 cases were lost to follow-up,1 case died of recurrence 9 months after surgery,the rest survived.Conclusion:Surgery is the preferred method for treating parapharyngeal space tumors and postoperative recurrence rate is pretty low.Endoscopy provides a new surgical management method,helping to reduce postoperative complications and recurrence rate.

Association of a Proactive Swallowing Rehabilitation Program With Feeding Tube Placement in Patients Treated for Pharyngeal Cancer.

Importance: A proactive speech and language pathology (SLP) program is an important component of the multidisciplinary care of patients with head and neck squamous cell carcinoma (HNSCC). Swallowing rehabilitation can reduce the rate of feeding tube placement, thereby significantly improving quality of life. Objective: To evaluate the initiation of a proactive SLP rehabilitation program at a single institution and its association with rates of feeding tube placement and dietary intake in patients with HNSCC. Design, Setting, and Participants: Cohort study at a tertiary care and referral center for patients with HNSCC serving the northern Chicago region. Patients were treated for squamous cell carcinomas of the hypopharynx, oropharynx, and nasopharynx from 2004 to 2015 with radiation or chemoradiation therapy in the definitive or adjuvant setting. Patients who received less than 5000 cGy radiation or underwent reirradiation were excluded. Interventions: A proactive SLP program for patients with HNSCC was initiated in 2011. Study cohorts were divided into 2 groups: 2004 through 2010 and 2011 through 2015. Main Outcomes and Measures: Primary outcome variables were SLP referral placement and timing of the referral. Secondary outcomes were feeding tube placement and ability to tolerate any oral intake. Results: A total of 254 patients met inclusion criteria (135 before and 119 after implementation of SLP program; median age, 60 years [range, 14-94 years]; 77% male). With the initiation of a proactive SLP program, pretreatment evaluations increased from 29 (21.5%) to 70 (58.8%; risk ratio [RR], 2.74; 95% CI, 1.92-3.91), and rate of referral overall at any time increased from 60.0% to 79.8% (RR, 1.33; 95% CI, 1.13-1.57). Feeding tube placement rates decreased from 45.9% (n = 62) to 29.4% (n = 35; RR, 0.64; 95% CI, 0.46-0.89). Among patients receiving a swallow evaluation, feeding tube requirements were less frequent for those receiving a pretreatment evaluation (31 of 99 [31%]) than for those referred during (11 of 18 [61%]) or after (38 of 59 [64%]) treatment. The rate of tolerating any oral intake at the end of treatment improved from 71.1% (n = 96) in the preimplementation period to 82.4% (n = 98; RR, 1.16; 95% CI, 1.01-1.33). Conclusions and Relevance: A proactive SLP program can be successfully established as part of the multidisciplinary care of patients with HNSCC and improve patient quality of life.

Bilateral pyriform sinus parathyroid adenomas.

Parathyroid glands undergo a variable descent during embryologic development and can be found anywhere in the neck from the level of the mandible to the mediastinum. To the best of our knowledge, we present the first report of a patient who was found to have bilateral parathyroid adenomas in her pyriform sinuses. A middle-aged woman with renal failure and secondary hyperparathyroidism presented with dysphagia and was found to have bilateral pyriform sinus masses on endoscopy. We performed direct laryngoscopy and surgical excision of these masses, and they were found to be parathyroid adenomas. Her dysphagia improved postoperatively, and she continues to be followed by her endocrinologist, who manages her secondary hyperparathyroidism medically. The differential diagnosis for hypopharyngeal masses is wide and should include parathyroid adenomas, even in patients with bilateral masses.