Neurofibromatosis type 2 with mild Pierre-Robin sequence showing a heterozygous chromosome 22q12 microdeletion encompassing NF2 and MN1.

Pierre-Robin sequence (PRS) is a rare, congenital defect presenting with micrognathia, glossoptosis, and airway obstruction with variable inclusion of a cleft palate. Overlapping PRS with neurofibromatosis type 2 (NF2) is a syndrome caused by a chromosome 22q12 microdeletion including NF2. We describe a patient with severe early-onset NF2 overlapping with PRS that showed micrognathia, glossoptosis, and a mild form of cleft palate. We detected a de novo chromosome 22q12 microdeletion including MN1 and NF2 in the patient. Previous cases of overlapping PRS and NF2 caused by the chromosome 22q12 microdeletions showed severe NF2 phenotypes with variable severity of cleft palate and microdeletions of varying sizes. Genotype-phenotype correlations and comparison of the size and breakpoint of microdeletions suggest that some modifier genes distal to MN1 and NF2 might be linked to the cleft palate severity.

Differences in responsiveness of intratympanic steroid injection for intractable vertigo in Meniere's disease.

OBJECTIVES: The efficacy of intratympanic steroid (ITS) injection for intractable Meniere's disease has been reported; however, its differences in responsiveness are not fully understood. This study investigated the clinical characteristics of patients who responded to ITS injection treatment. METHODS: This retrospective study included 32 patients with Meniere's disease who were unable to control frequent vertigo attacks despite conservative treatment for at least 3 months. They received an intratympanic injection of dexamethasone (3.3 mg/mL) in the affected side at least three times. We measured hearing threshold, subjective symptom scores, cervical and ocular vestibular evoked myogenic potential (cVEMP and oVEMP), and performed glycerol and bithermal caloric tests. RESULTS: Satisfactory control of vertigo for 1 year after the first round of injection was found in 18 patients (56.3%; the response group). However, the injections failed to control vertigo in the other 14 patients (43.8%; the non-response group), and they were then treated with middle ear micropressure therapy. The response group showed improvement in low-frequency hearing, whereas hearing acuity did not change in the non-response group. Significantly reduced amplitude of cVEMP on the affected side was found in 62.5% of patients in the response group; however, no patients in the non-response group showed reduced amplitude of cVEMP. CONCLUSIONS: ITS injection significantly improved the subjective symptoms for intractable Meniere's disease; however, the long-term effects were heterogeneous. Our results suggest that reduced amplitude in cVEMP is associated with the effectiveness of ITS injection treatment.

Hearing loss is associated with hippocampal atrophy and high cortisol/dehydroepiandrosterone sulphate ratio in older adults.

OBJECTIVES: Hearing loss (HL) has been recognised as a prodromal symptom of cognitive disorder with aging. It is still uncertain if HL leads to cognitive impairment directly or through an indirect mechanism. DESIGN: Participants of this study underwent an auditory test, blood tests, and brain MRI. The atrophy rate of the hippocampus (HP) was calculated using voxel-based specific areas. A partial correlation analysis whilst controlling for the effect of age was performed to analyse the factors affecting hearing levels and HP atrophy rate (HP%). STUDY SAMPLE: Thirty-six older adults with hearing impairment. RESULTS: The group of participants with moderate or severe HL (n = 22) had higher cortisol/dehydroepiandrosterone sulphate (C/D) ratio, geriatric depression score (GDS) and HP% than the mild HL or normal hearing group (n = 14, p < 0.05). The HP% showed a significant positive correlation with the C/D ratio, GDS and the hearing level of high frequency (HF) (p < 0.05). The C/D ratio was positively correlated with the HP% and the hearing level of the HF (p < 0.05). CONCLUSIONS: Our results suggest that the HL is associated with the atrophy of HP and high C/D ratios in older adults; however, HL may not be causally related to hippocampal atrophy.

Diagnostic ability of contrast-enhanced computed tomography for metastatic cervical nodes in head and neck squamous cell carcinomas: significance of additional coronal reconstruction images.

PURPOSE: To evaluate the significance of additional coronal reconstruction images in the diagnostic ability of contrast-enhanced computed tomography (CECT) for metastatic cervical nodes in patients with head and neck squamous cell carcinomas (HNSCC). MATERIAL AND METHODS: We retrospectively assessed 97 metastatic and 141 reactive histologically proven cervical nodes of 38 patients with HNSCC, who underwent CECT before neck dissection. Observer #1, an expert radiologist in head and neck imaging, and observer #2, a general radiologist, reviewed all CECT images. The observers first assessed the presence of nodal metastasis using axial CECT alone (A-CECT). Three days later, they reassessed its presence using combined axial and coronal CECT (A&C-CECT). RESULTS: The sensitivity of A-CECT vs. A&C-CECT was 73.2% vs. 75.3% for observer #1 (p = 0.73) and 69.1% vs. 69.1% for observer #2 (p = 1.00), respectively. The specificity of A-CECT versus A&C-CECT was 92.2% vs. 97.2% for observer #1 (p < 0.05) and 92.9% vs. 95.7% for observer #2 (p = 0.22), respectively. The accuracy of A-CECT versus A&C-CECT was 84.5% vs. 88.2% for observer #1 (p < 0.05) and 83.2% vs. 85.3% for observer #2 (p = 0.30), respectively. The area under the curve (AUC) of A-CECT vs. A&C-CECT was 0.86 vs. 0.91 for observer #1 (p < 0.05) and 0.85 vs. 0.85 for observer #2 (p = 0.80), respectively. CONCLUSIONS: The specificity, accuracy, and AUC increased with the use of coronal images during the assessment by the expert radiologist. The appropriate use of coronal images allowed proper configuration recognition and improved diagnostic ability.

CT and MR imaging findings of infection-free and benign second branchial cleft cysts.

PURPOSE: The present study aimed to assess CT and MR imaging findings of infection-free and benign second branchial cleft cysts (SBCCs). METHODS: Eleven patients with histopathologically confirmed infection-free and benign SBCCs underwent preoperative contrast-enhanced CT (CECT) and/or MR imaging. We assessed qualitative (presence and extent of wall thickening, degree of contrast enhancement of the thickened wall on CECT images, and signal intensity of the thickened wall on T2-weighted images) and quantitative (maximum thickness of the thickened wall) imaging findings. RESULTS: Eccentric and smooth wall thickening was observed in 11/11 (100%) patients. The wall thickening extent (percentage of the thickened wall to the circumference of the wall) was small (1%-25%) in 4/11 (36%), moderate (26%-50%) in 6/11 (54%), extensive (51%-75%) in 1/11 (9%), and diffuse (76%-100%) in 0/11 (0%) patients. Mild homogeneous enhancement of the thickened wall on CECT images was observed in 7/7 (100%) patients. The signal intensity of the thickened wall on T2-weighted images was isointense relative to that of normal lymph nodes in 7/8 (88%) and mildly hyperintense in 1/8 (12%) patient. The maximum thickness of the thickened walls ranged from 2 to 4 (mean 3.4) mm. CONCLUSIONS: Infection-free and benign SBCCs are identifiable as cysts with eccentric and smooth wall thickening on CECT and MR images. The wall thickness was almost always less than half of the wall circumference, isointense relative to normal lymph nodes, and showed mild homogeneous enhancement.

M2-like macrophage polarization in high lactic acid-producing head and neck cancer.

Reprogramming of glucose metabolism in tumor cells is referred to as the Warburg effect and results in increased lactic acid secretion into the tumor microenvironment. We have previously shown that lactic acid has important roles as a pro-inflammatory and immunosuppressive mediator and promotes tumor progression. In this study, we examined the relationship between the lactic acid concentration and expression of LDHA and GLUT1, which are related to the Warburg effect, in human head and neck squamous cell carcinoma (HNSCC). Tumors expressing lower levels of LDHA and GLUT1 had a higher concentration of lactic acid than those with higher LDHA and GLUT1 expression. Lactic acid also suppressed the expression of LDHA and GLUT1 in vitro. We previously reported that lactic acid enhances expression of an M2 macrophage marker, ARG1, in murine macrophages. Therefore, we investigated the relationship between the lactic acid concentration and polarization of M2 macrophages in HNSCC by measuring the expression of M2 macrophage markers, CSF1R and CD163, normalized using a pan-macrophage marker, CD68. Tumors with lower levels of CD68 showed a higher concentration of lactic acid, whereas those with higher levels of CSF1R showed a significantly higher concentration of lactic acid. A similar tendency was observed for CD163. These results suggest that tumor-secreted lactic acid is linked to the reduction of macrophages in tumors and promotes induction of M2-like macrophage polarization in human HNSCC.

[Eight Cases of Small Cell Neuroendocrine Carcinoma of the Head and Neck].

Small cell neuroendocrine carcinoma of the head and neck is a rarely occurring poorly differentiated and high-grade malignant neoplasm characterized by highly active proliferation of neuroendocrine tumor cells. There are no established therapies for this disease. To clarify the clinical course and develop effective treatment(s) for the carcinoma, we reviewed the data of 8 patients of small cell neuroendocrine carcinoma of the head and neck treated by us between 2006 and 2014 at the Department of Otolaryngology, Gifu University School of Medicine and our affiliated hospitals. The patients consisted of 3 men and 5 women, ranging in age from 38 to 84 years old (mean : 60.9 years). The tumor arose from the nasal cavity or the paranasal sinuses in 3 cases, from the parotid grand in 2 cases, from the oropharynx in 2 cases, and from the hypopharynx in 1 case. The tumor that arose from the hypopharynx was a combined small-cell carcinoma with squamous cell carcinomas, and the one that arose from the oropharynx had already metastasized to the brain. Most of the patients were treated by chemotherapy and radiotherapy based on the treatment employed for small cell carcinoma of the lung. Only the patient in whom the tumor arose from a paranasal sinus was treated by surgery despite the definitive diagnosis of small cell carcinoma. We selected CPT-11 and a platinum agent for 4 patients, and VP-16 and a platinum agent for 3 patients as the first-line chemotherapy. Although two patients showed carcinoma-free survival, one died of recurrence of the regional lymph node metastases and five died of distant metastases despite the absence of locoregional recurrence. The 5-year survival rate was a dismal 25%, suggesting that we need to establish effective treatment(s) for the control of distant metastases in cases of the small cell neuroendocrine carcinoma of the head and neck.

Gorham-Stout Disease of the Skull Base With Hearing Loss: Dramatic Recovery and Antiangiogenic Therapy.

Gorham-Stout disease (GSD) is a rare disorder of unknown etiology. We present a 6-year-old male with GSD involving the skull base who presented with recurrent cerebrospinal fluid (CSF) rhinorrhea, severe hearing loss, and facial palsy secondary to cerebellar herniation into the internal auditory canal. After 2 months of treatment with pegylated interferon (IFN) α-2b (50 µg/week), his hearing recovered dramatically. Two years later, new bone formation appeared radiologically and IFN was switched to sirolimus. One year after the switch, CSF rhinorrhea disappeared. Antiangiogenic therapy might inhibit proliferation of vascular endothelial cells in osteolytic lesions and lead to new bone formation.

[A case of idiopathic neck bleeding from a parathyroid cyst].

Bleeding from parathyroid cysts is rare. The retropharyngeal space has a very soft structure and if bleeding spreads to this space, airway obstruction can easily occur. We report on a 50-year-old female case with idiopathic neck bleeding from a left parathyroid cyst without any episode of injury. The patient complained of neck swelling after exercise and went to a nearby hospital. At the hospital, the doctor thought this swelling was caused by retropharyngeal bleeding from a tumor behind the left thyroid gland. Embolization of the left thyroid artery was performed. However, the next day, airway obstruction.was occurred and she was brought to our hospital. An emergency operation was performed to open the left neck swelling region. The operation findings and pathological examination showed that the bleeding was caused by a parathyroid cyst and airway obstruction had occurred because of retropharyngeal edema. In this case, the bleeding may have been caused by torsion of the neck when the patient exercised. The retropharyngeal edema probably resulted from the delay of delivery of the lymphatic and venous return and the arterial embolization. 1 year after the operation, the patient is very well and there has been no recurrence.

Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity.

The activation of oncogenic signaling pathways induces the reprogramming of glucose metabolism in tumor cells and increases lactic acid secretion into the tumor microenvironment. This is a well-known characteristic of tumor cells, termed the Warburg effect, and is a candidate target for antitumor therapy. Previous reports show that lactic acid secreted by tumor cells is a proinflammatory mediator that activates the IL-23/IL-17 pathway, thereby inducing inflammation, angiogenesis and tissue remodeling. Here, we show that lactic acid, or more specifically the acidification it causes, increases arginase I (ARG1) expression in macrophages to inhibit T-cell proliferation and activation. Accordingly, we hypothesized that counteraction of the immune effects by lactic acid might suppress tumor development. We show that dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinases, targets macrophages to suppress activation of the IL-23/IL-17 pathway and the expression of ARG1 by lactic acid. Furthermore, lactic acid-pretreated macrophages inhibited CD8+ T-cell proliferation, but CD8+ T-cell proliferation was restored when macrophages were pretreated with lactic acid and DCA. DCA treatment decreased ARG1 expression in tumor-infiltrating immune cells and increased the number of IFN-γ-producing CD8+ T cells and NK cells in tumor-bearing mouse spleen. Although DCA treatment alone did not suppress tumor growth, it increased antitumor immunotherapeutic activity of Poly(IC) in both CD8+ T cell- and NK cell-sensitive tumor models. Therefore, DCA acts not only on tumor cells to suppress glycolysis but also on immune cells to improve the immune status modulated by lactic acid and to increase the effectiveness of antitumor immunotherapy.

Effect of lyophilized powder made from enzymolyzed honeybee larvae on tinnitus-related symptoms, hearing levels, and hypothalamus-pituitary-adrenal axis-related hormones.

OBJECTIVES: Tinnitus interferes with sleep and concentration which is associated with depression; however, no drug has been effective in treating tinnitus. Our purpose is to evaluate our hypothesis that the treatment with lyophilized powder of enzymolyzed honeybee larvae as a complementary medicine may provide a therapeutic effect on tinnitus-related symptoms. DESIGN: Sixty tinnitus sufferers participated in a randomized double-blind placebo-controlled trial using the lyophilized powder of enzymolyzed honeybee larvae or a placebo. The Tinnitus Handicap Inventory, a visual analog scale to rate the severity of tinnitus, hearing levels, and hypothalamus-pituitary-adrenal axis-related hormones drawn early in the morning were measured upon entry into the study and after 12 wk of follow-up. RESULTS: The lyophilized powder of enzymolyzed honeybee larvae was not superior to placebo with regard to the total score on the Tinnitus Handicap Inventory and the visual analog scale. However, subjects in the honeybee larvae group showed significant improvements in some items about depression associated with tinnitus, whereas subjects in the placebo group showed no improvement in any items. The honeybee larvae group showed significant improvements in the hearing levels at 2 and 4 kHz in the audiogram of the better ear. The intervention of the lyophilized powder of enzymolyzed honeybee larvae was associated with lower serum cortisol levels, serum prolactin levels, and cortisol/dehydroepiandrosterone sulfate ratios. The ratios in the placebo group significantly were increased. CONCLUSIONS: Our results suggest that the lyophilized powder of enzymolyzed honeybee larvae represents an effective complementary medicine to alleviate depression associated with tinnitus by regulating the activity of the hypothalamus-pituitary-adrenal axis.

[Surgery in the lateral area of the cervicothoracic border].

Surgery is not usually indicated for the involvement of cervical lymph node metastasis to the subclavian vein. Although surgery is indicated for the involvement of cervical lymph node metastasis to the venous angle, the usual visual field associated with cervical lymph node dissection cannot sufficiently visualize the subclavian vein, and the possibility exists of causing great vessel injury when involved lymph nodes are large and their mobility is restricted. In such cases, surgical excision may be avoided based on the expectation that ligating or cutting the internal jugular vein will be difficult. We examined 10 patients who underwent surgery for the adhesion or invasion of the primary tumor or involved lymph nodes to the venous angle or subclavian vein. The clavicle was removed or displaced to secure the visual field. The sternoclavicular joint was conserved and the clavicle, separated from the first rib, was lifted in 4 patients, while the medial two thirds of the clavicle was removed in 6 patients. Involved lymph nodes could be securely dissected without causing great vessel injury. A chylous leak occurred in one patient undergoing the procedure on the left side.

Serum Fibrinogen Level and Cytokine Production as Prognostic Biomarkers for Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVES: No clinically useful prognostic factors have been identified for idiopathic sudden sensorineural hearing loss (ISSNHL). The current study therefore sought to identify useful prognostic factors for idiopathic sudden sensorineural hearing loss from blood biomarkers while attempting to classify the pathogenic mechanism and formulate treatment strategies based on these results. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. METHODS: A total of 47 patients with acute phase ISSNHL were treated with steroid at an initial dose of 1 mg/kg/day and hyperbaric oxygen therapy and followed up for 6 months. Serum fibrinogen levels, peripheral blood mononu- clear cells (PBMCs), and interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α production levels from PBMCs were measured, after which patient's pre- and post- treatment hearing was compared. RESULTS: In the overall cohort, the mean improvement level, mean recovery rate, and mean fibrinogen level was 20.3 dB, 46.2%, 292.0 mg/mL, respectively. The mean levels of IL-1ß, IL-6, and TNF-α produced by peripheral blood mononu- clear cells cultured under lipopolysaccharide stimulation were 318.4, 498.1, and 857.6 pg/mL, respectively. High fibrinogen levels were associated with poor hearing progno- sis. Lipopolysaccharide-stimulated cytokine production by PBMCs did not correlate with hearing changes; however, the prognosis was significantly better in patients with low fibrinogen levels and high IL-1ß levels produced by PBMCs than in other patients. CONCLUSIONS: Our results suggest that patients with simple inflammatory-type ISSNHL responded well to standard therapy. Therefore, serum fibrinogen levels and PBMCs cytokine production may help determine the management of ISSNHL based on its pathogenic mechanism.

Genetic Panel Test of Double Cancer of Signet-Ring Cell/Histiocytoid Carcinoma of the Eyelid and Papillary Thyroid Carcinoma: Case Report and Literature Review.

Signet-ring cell/histiocytoid carcinoma (SRCHC) is a rare, aggressive neoplasm that often originates in the eyelid. We present a rare case of a 64-year-old male with SRCHC and papillary thyroid carcinoma (PTC) that underwent exome panel sequencing with next-generation sequencing (NGS). In addition, we reviewed reports of genetic mutations in SRCHC and compared them with our results. The imaging findings allowed us to recognize the differences in pathology between the left and right cervical nodes. For first-line treatment, an extended total maxillectomy with orbital exenteration and dissection of the left neck was performed. Two months later, total thyroidectomy and right neck dissection were performed. Two years after surgery, multiple bone metastases occurred. An exome panel sequence with NGS was used to determine the chemotherapy regimen. Notably, somatic mutations in cadherin 1 (CDH1), human epidermal growth factor receptor 2 (ERBB2), neurofibromin 1 (NF1), and tumor protein p53 (TP53) were detected. These mutations are rarely detected in PTC; therefore, cervical metastases are assumed to originate from SRCHC. To our knowledge, there have been no reports of simultaneous cancer of SRCHC and PTC. Somatic mutations in CDH1, ERBB2, NF1, and TP53 were detected in the exome panel sequence of the metastatic lymph nodes of SRCHC and correlated with previous reports of SRCHC.

The relevance of hypothalamus-pituitary-adrenocortical axis-related hormones to the cochlear symptoms in Ménière's disease.

OBJECTIVE: To investigate the association of the HPA (hypothalamus-pituitary-adrenocortical) axis-related hormones with the progression of cochlear symptoms in patients with Ménière's disease. DESIGN: Clinical assessments (Tinnitus Handicap Inventory: THI, visual analog scale to rate the degree of the tinnitus: VAS, hearing levels in pure-tone audiometry) were conducted upon entry into the study (baseline) and at 12 weeks follow-up (week 12). Blood sampling to measure HPA axis-related hormones took place between 9:00 and 10:00 a.m. at baseline and at 12 weeks follow-up. STUDY SAMPLES: This study consisted of 20 unilateral Ménière's disease patients and 21 patients with other diseases with unilateral sensorineural hearing loss and tinnitus. RESULTS: A significant deterioration of the hearing level at high frequency range, especially at 2 kHz, was found during the 12 weeks follow-up in the Ménière's disease group (p < 0.05). The average hearing levels significantly correlated with the serum cortisol level at baseline and week 12 in the Ménière's disease group, especially regarding the high frequency levels (p < 0.01). CONCLUSIONS: Our results suggest that the cortisol levels influence the endolymphatic homeostasis resulting in a deterioration of hearing at high frequency with upstaging of Ménière's disease.

[Superior semicircular canal dehiscence syndrome treated by calcium phosphate cement canal plugging: a case report].

Superior semicircular canal dehiscence (SCD) syndrome exhibits pressure- and/or sound-induced oscillopsia and vertigo due to an absence of bone overlaying the superior semicircular canal. A 33-year-old man with right-ear SCD reported dizziness in a noisy hall three years earlier followed by dizziness during flatulence, straining or coughing, and right-ear autophony. Audiography showed a right-ear low-frequency air-bone gap, with positive Tullio phenomenon and a Valsalva maneuver against closed glottis causing torsional-vertical nystagmus. Temporal-bone computed tomography (CT) led to a diagnosis of right-ear SCD syndrome. Surgical dehiscence plugging with calcium phosphate cement via the middle fossa resolved vestibular and cochlear symptoms in the more than two years since.

Open penetrating external laryngotracheal injury and abdominal trauma by suicide attempt successfully treated with immediate intervention: A case report.

An open penetrating external laryngotracheal injury (PE-LTI) is a rare life-threatening injury requiring immediate intervention. Penetrating injuries may cause tissue loss, which makes wound closure difficult sometimes. Here, we report the case of an open PE-LTI and abdominal trauma by suicide attempt. A 38-year-old Asian man with depression was found in his home after having cut his own neck and abdomen. He was transported to a regional trauma center and immediately intubated. On arrival, his blood pressure was 120/90 mmHg and heart rate was 120 beats/min. Physical examination revealed three cuts each on the neck and abdomen and no dysphonia. The patient's condition was diagnosed as an open PE-LTI, classified as group 5 on the Schaefer classification system and zone II on the Roon and Christensen classification system. He was also evaluated for possible mesenteric injury. We performed an emergency primary laryngotracheal repair and exploratory laparotomy. There was no obvious blood vessel injury, but soft and cartilage tissues were crushed and disconnected completely. On day 8, he underwent wound closure and tracheostomy on the caudal side of the wound. He was successfully weaned from mechanical ventilation on day 9, transferred to the general ward on day 13, decannulated on day 63, and discharged from the hospital thereafter for subacute care. In this case of severe neck injury with complete laryngotracheal separation, tissue losses were relatively minimal. Wound closure presumably occurred early in the absence of blood vessel injury.

"Flow-void" sign at MR imaging: a rare finding of extracranial head and neck schwannomas.

The authors present two cases of extracranial head and neck schwannomas that exhibited the "flow-void" sign at MR imaging. In the described cases, MR images showed intratumoral signal voids, which corresponded to dilated vessels. Dynamic contrast-enhanced CT also demonstrated dilated vessels within the tumors on the arterial phase and tumor parenchymal enhancement on the delayed phase. Histopathologic examinations of excised specimens revealed thin-walled, dilated abnormal vessels with or without hyaline degeneration. Schwannoma should be considered when MR images demonstrate the "flow-void" sign in extracranial head and neck tumors.

The association of the plasma vasopressin level during attacks with a prognosis of Meniere's disease.

An elevation of the plasma arginine vasopressin (AVP) level has frequently been observed in Meniere's disease patients. However, little is known regarding the mechanism behind this elevation. The plasma AVP levels in acute phase were determined in 21 Meniere's disease patients and 16 patients with other types of vertigo. The plasma AVP levels of Meniere's disease patients in the acute phase were significantly higher than in those of other vertigo patients (p < 0.01). In Meniere's disease patients with abnormally high levels of AVP (more than 3.5 pg/ml) in the acute phase, 36% of patients were resistant to conservative treatments for frequent vertigo attacks for the follow-up period of at least 2years. A significant correlation was observed between the plasma AVP in the acute phase and the highest hearing threshold level at a frequency of 1kHz for the follow-up period of at least 1 year (r=0.45, p < 0.05). These results suggest that the elevation in plasma AVP level in the acute phase is associated with the prognosis of Meniere's disease.

The importance of FDG-PET/CT parameters for the assessment of the immune status in advanced HNSCC.

OBJECTIVE: Cancer cells secrete large amounts of lactic acid via aerobic glycolysis. We have shown that lactic acid plays an important role as a proinflammatory and immunosuppressive mediator and promotes tumor progression. Fluorine-18 fluorodeoxyglucose (FDG) uptake detected by positron emission tomography/computed tomography (PET/CT) is considered as a good indicator of aerobic glycolysis in cancer. In this study, we examined the relationships between systemic inflammatory parameters and FDG-PET/CT parameters in advanced head and neck squamous cell carcinoma (HNSCC). Furthermore, we investigated the relationships between FDG-PET/CT parameters and M2-macrophage polarization in HNSCC by assessing the ratio of CD163, a M2-macrophage marker, to CD68, a pan-macrophage marker. METHODS: This study included 73 advanced HNSCC patients. We assessed the C-reactive protein (CRP) level, white blood cell (WBC) count, neutrophil count, lymphocyte count, and monocyte count as systemic inflammatory markers. Additionally, we assessed the maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) as FDG-PET/CT parameters. RESULTS: The CRP level, WBC count, and neutrophil count were correlated with whole-body FDG-PET/CT parameters. The CD163/CD68 ratio was correlated with SUVmax and SUVmean. Our results suggest that systemic inflammation, which is associated with neutrophils, develops in patients with HNSCC having tumors with a larger volume and increased glucose uptake and that M2-macrophage polarization is promoted in HNSCC with increased glucose uptake, SUVmax, and SUVmean. FDG-PET/CT has the potential to reflect cancer-related chronic inflammation and immunosuppressive conditions in cancer patients. CONCLUSIONS: FDG-PET/CT parameters appear to be useful in assessing the immune status in HNSCC.