Metabolic profiling analysis of head and neck squamous cell carcinoma.

OBJECTIVE: Tumor cells can acquire a large amount of energy and structural components by reprogramming energy metabolism; moreover, metabolic profiles slightly differ according to cancer type. This study compared and assessed the metabolic profile of head and neck squamous cell carcinoma (HNSCC) and normal tissues, which were collected from patients without cancer. SUBJECTS AND METHODS: Overall, 23 patients with HNSCC and 6 patients without cancer were included in the analysis. Metabolomic profiles were analyzed using capillary electrophoresis-mass spectrometry. Gene expression was evaluated using real-time reverse transcription-polymerase chain reaction. RESULTS: Glycolysis, the pentose phosphate pathway, tricarboxylic acid cycle, and glutamine metabolism were upregulated in HNSCC tissues based on gene expression analysis. HNSCC could then have enhanced energy production and structural component. The levels of lactate, succinate, glutathione, 2-hydroxyglutarate, and S-adenosylmethionine, considered as oncometabolites, increased and these had accumulated in HNSCC tissues. CONCLUSIONS: The level of metabolites and the expression of enzymes differ between HNSCC and normal tissues. Reprogramming metabolism in HNSCC provides an energy source as well as structural components, creating a system that offers rapid proliferation, progression, and is less likely to be eliminated.

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.

[The Warburg Effect and M2 Macrophage Polarization in Head and Neck Cancer].

Reprogramming of glucose metabolism in tumor cells is referred to as the Warburg effect. The Warburg effect is caused by tumor cells not only to adapt their metabolism to the demand for and limited supply of oxygen but also to obtain large amounts of nucleotides, amino acids and lipids for excessive proliferation of tumor cells. The Warburg effect results in increased production of lactic acid, as the final product of glycolysis, in the tumor microenvironment. Lactic acid secreted by tumor cells functions as an immunosuppressive mediator and converts macrophages into M2 macrophages. M2 macrophages reduce inflammatory responses and adaptive Th1 immunity, and promote angiogenesis and tissue remodeling. Tumor-associated macrophages(TAMs)polarize into the M2 phenotype and suppress the host anti-cancer immune response, leading to tumor progression. We have demonstrated that tumor-secreted lactic acid is linked to the induction of M2-macrophage polarization in human head and neck squamous cell carcinoma(HNSCC). FDG, which is a glucose analog, uptake measured by positron emission tomography/computed tomography(PET/CT)indicates the Warburg effect in tumor tissue. M2-macrophage polarization is promoted in HNSCC with increased glucose uptake, maximum standardized uptake value(SUVmax), mean SUV(SUVmean). Tumor cells mediate an immunosuppressive microenvironment via inducing M2-macrophage polarization by reprogramming of glucose metabolism, called Warburg effect.

Development of a vaccine based on bacteria-mimicking tumor cells coated with novel engineered toll-like receptor 2 ligands.

For a successful tumor vaccine, it is necessary to develop effective immuno-adjuvants and identify specific tumor antigens. Tumor cells obtained from surgical or biopsy tissues are a good source of tumor antigens but, unlike bacteria, they do not induce strong immune responses. Here, we designed 2 novel lipopeptides that coat tumor cell surfaces and mimic bacterial components. Tumor cells coated with these lipopeptides (called bacteria-mimicking tumor cells [BMTC]) were prepared and their efficacy as a tumor vaccine examined. Natural bacterial lipopeptides act as ligands for toll-like receptor 2 (TLR2) and activate dendritic cells (DC). To increase the affinity of the developed lipopeptides for the negatively charged plasma membrane, a cationic polypeptide was connected to Pam2Cys (P2C), which is the basic structure of the TLR2 ligand. This increased the non-specific binding affinity of the peptides for the cell surface. Two such lipopeptides, P2CSK11 (containing 1 serine and 11 lysine residues) and P2CSR11 (containing 1 serine and 11 arginine residues) bound to irradiated tumor cells via the long cationic polypeptides more efficiently than the natural lipopeptide MALP2 (P2C-GNNDESNISFKEK) or a synthetic lipopeptide P2CSK4 (a short cationic polypeptide containing 1 serine and 4 lysines). BMTC coated with P2CSR11 or P2CSK11 were efficiently phagocytosed by DC and induced antigen cross-presentation in vitro. They also induced effective tumor-specific cytotoxic T cell responses and inhibited tumor growth in in vivo mouse models. P2CSR11 activated DC but induced less inflammation-inducing cytokines/interferons than other lipopeptides. Thus, P2CSR11 is a strong candidate antigen-specific immuno-adjuvant, with few adverse effects.

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.

Development of a dendritic cell-targeting lipopeptide as an immunoadjuvant that inhibits tumor growth without inducing local inflammation.

Materials used for the past 30 years as immunoadjuvants induce suboptimal antitumor immune responses and often cause undesirable local inflammation. Some bacterial lipopeptides that act as Toll-like receptor (TLR) 2 ligands activate immune cells as immunoadjuvants and induce antitumor effects. Here, we developed a new dendritic cell (DC)-targeting lipopeptide, h11c (P2C-ATPEDNGRSFS), which uses the CD11c-binding sequence of intracellular adhesion molecule-1 to selectively and efficiently activate DCs but not other immune cells. Although the h11c lipopeptide activated DCs similarly to an artificial lipopeptide, P2C-SKKKK (P2CSK4), via TLR2 in vitro, h11c induced more effective tumor inhibition than P2CSK4 at low doses in vivo with tumor antigens. Even without tumor antigens, h11c lipopeptide significantly inhibited tumor growth and induced tumor-specific cytotoxic T cells. P2CSK4 was retained subcutaneously at the vaccination site and induced severe local inflammation in in vivo experiments. In contrast, h11c was not retained at the vaccination site and was transported into the tumor within 24 hr. The recruitment of DCs into the tumor was induced by h11c more effectively, while P2CSK4 induced the accumulation of neutrophils leading to severe inflammation at the vaccination site. Because CD11b+ cells, but not CD11c+ cells, produced neutrophil chemotactic factors such as macrophage inflammatory protein (MIP)-2 in response to stimulation with TLR2 ligands, the DC-targeting lipopeptide h11c induced less MIP-2 production by splenocytes than P2CSK4. In this study, we succeeded in developing a novel immunoadjuvant, h11c, which effectively induces antitumor activity without adverse effects such as local inflammation via the selective activation of DCs.

Botulinum toxin injection for abductor spasmodic dysphonia under cervical ultrasonography guidance.

Ultrasound (US) imaging effectively provides real-time anatomical information for clinical examinations. In otolaryngology, US imaging can visualize laryngeal muscles as well as cervical muscles. Here we present the case where US imaging was used while injecting botulinum toxin (BT) for the treatment of abductor spasmodic dysphonia, which provided definite results. We could visualize not only the injection pathway but also the infiltration of the BT solution into the posterior cricoarytenoid muscles. Therefore, our laryngeal US imaging is useful for both improving the success rate and avoiding injection complications of BT.

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.

Usefulness of intraoperative monitoring for mesenteric lymph node metastasis in transplanted free jejunum.

We herein report a rare case of a patient with hypopharyngeal squamous cell carcinoma (SCC) who presented with recurrent metastasis in the mesenteric lymph node of a transplanted jejunum. Removal of the metastatic lymph node required resection of the nutrient vessels which risked the current state of the transplanted jejunum. Importantly, although the nutrient vessels were resected, the jejunum did not become necrotic. This case and another similar case indicate that it may be possible to predict the viability of a transplanted jejunum where jejunal nutrient vessels must subsequently be resected. Key indicators for jejunal survival include determining jejunal blood flow by intraoperative indocyanine green fluorescence imaging, confirming good jejunal color and observation of peristaltic movement by intraoperative blood flow blockage of nutrient vessels. In conclusion, if intraoperative indocyanine green fluorescence imaging in the entire jejunum can be confirmed, there is a high possibility that the jejunum can be well preserved. The clinical presentation and clinical course are described with a proposed new schema of the resectable site of the transplanted jejunal mesentery.

Comprehensive Genome profile testing in head and neck cancer.

OBJECTIVE: Head and neck cancer (HNC) is a tumor occurring in various primary sites with limited chemotherapy options for its treatment. Recently, comprehensive genomic profiling (CGP) testing has become clinically widespread. In this study, we examined the utility of CGP in diagnosing and treating HNC. METHODS: This study included 29 patients with HNC who underwent CGP testing at the Gifu University Hospital between December 2019 and April 2022. We analyzed the types of gene mutations and tumor mutational burden (TMB) based on the CGP results. Squamous cell carcinoma accounted for 55.2%, and other cancers accounted for 44.8%. And we investigated the correlation of prognosis with gene mutations and TMB. RESULTS: Gene mutations were detected in TP53(48.3%), CDKN2A (27.6%), CDKN2B (17.2%), NOTCH1 (17.2%), PIK3CA (17.2%), ARID1A (13.8%), and NF1 (13.8%). TP53, CDKN2A and CDKN2B mutations significantly decreased survival rate in HNC. Five cases (17.2%) were TMB-high and 82.8% were TMB-low. In SCC cases treated with immune checkpoint inhibitors, TMB-high had better Overall survival than TMB-low. And all patients with TMB-high were oropharyngeal cancer. CONCLUSION: Although there were no cases in which effective treatment was actually performed based on the results of CGP, many gene mutations have been detected and several gene mutations correlated with prognosis. Furthermore, TMB can be used as a biomarker to predict the therapeutic effects of immune checkpoint inhibitors in cases of SCC.

Bilateral Recurrent Laryngeal Nerve Paralysis Manifesting as Long COVID.

Management with ventilation is used for severe cases of coronavirus disease 2019 (COVID-19). After extubation, recurrent laryngeal nerve paralysis due to various factors may occur. Almost all cases of paralysis develop unilaterally; however, bilateral recurrent laryngeal nerve paralysis occurs rarely. Such cases may be fatal due to upper air obstruction, and patients are forced to adhere to restrictions after a tracheotomy. The present case illustrates bilateral recurrent laryngeal nerve paralysis that occurred 48 hours after withdrawal from the ventilator. A 75-year-old woman with a history of hypertension came to our hospital with a history of fever and cough for five days. She was diagnosed with pneumonia due to COVID-19 via polymerase chain reaction using her saliva, and ground-glass opacity was found in both lung fields on chest X-ray and computed tomography (CT). Mechanical ventilation, steroids, remdesivir, and baricitinib were administered. The patient's fever and oxygenation status improved with these treatments, and she was weaned from the ventilator on the eighth day of hospitalization. She had no symptoms immediately. However, 48 hours after extubation, bilateral recurrent laryngeal nerve paralysis was suspected. Thus, oral intubation was immediately introduced and a tracheostomy was performed. Vocal cord movement disorders continued for eight weeks, and during that period, the patient displayed hoarseness and suffered from dysphagia. We considered that nerve disorders from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in addition to the compression by the endotracheal tube, caused bilateral recurrent laryngeal nerve paralysis. The neural injury by SARS-CoV-2 may prolong and manifest as "Long COVID."

Immune-modified Glasgow prognostic score: A new prognostic marker for head and neck cancer.

BACKGROUND: The modified Glasgow prognostic score (mGPS) includes C-reactive protein and serum albumin levels and is a useful prognostic tool for malignant tumors. The immune system affects cancer progression and recurrence and treatment response. We hypothesized that increasing the lymphocyte count improves mGPS, and we created a new prognostic marker termed immune-mGPS (imGPS). METHODS: This study included 461 patients with head and neck squamous cell carcinoma (HNSCC). The imGPS was calculated as the conventional mGPS with one additional point for a low lymphocyte count (<1250/µL). RESULTS: Addition of the lymphocyte count to mGPS significantly increased the area under the time-dependent receiver operating characteristic curve for overall and progression-free survivals. The added predictive abilities of this tool were supported by improvement in both net reclassification and integrated discrimination. CONCLUSION: imGPS is a more accurate predictor of clinical outcome in patients with HNSCC than mGPS.

Posterior ischemic optic neuropathy following postoperative bleeding and internal jugular vein compression.

Perioperative blindness, especially posterior ischemic optic neuropathy (PION), is an uncommon but potentially devastating complication. We report a case of a 65-year-old male patient who underwent laryngopharyngectomy, bilateral neck dissection, and free jejunum flap reconstruction, but then experienced PION in his right eye following postoperative bleeding and bilateral internal jugular veins (IJVs) compression. Despite systemic corticosteroid therapy, his visual recovery prognosis was poor. The specific mechanism responsible for PION remains unclear, and no therapy has been shown to improve this condition. As such, prevention of perioperative PION remains the only available strategy. Surgeons should be aware of this rare potential complication and its risk factors and strive to avoid it. As postoperative bleeding and IJV compression are one of important risk factors for PION, avoiding these are critical.

A Case of Thyroid Carcinoma Showing Thymus-Like Differentiation With Breast Cancer Susceptibility Gene 2 Mutation: A Case Report and Literature Review.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant tumor that originates from ectopic thymic or residual embryonic tissues. CASTLE is specified as a synonym for intrathyroidal thymic carcinoma. The patient is a 66-year-old male. Surgery was performed on the thyroid tumor with tracheal infiltration, and pathological examination revealed CASTLE. Multidisciplinary treatment, including chemoradiotherapy, was performed for recurrent tumors, and he has been alive for 90 months since the initial treatment. The cancer genome panel identified mutations in AT-rich interaction domain 1A(ARID1A)and breast cancer susceptibility gene 2 (BRCA2), but there were no available clinical trials or recommended drugs. BRCA2 may be involved in CASTLE. Herein, we review the literature and report the treatment method and gene mutation for recurrent metastatic cases of CASTLE, for which standard treatment has not been established.

Nonsurgical Treatment Strategies for Elderly Head and Neck Cancer Patients: An Emerging Subject Worldwide.

Consistent with the increasing rate of head and neck cancers among elderly adults, there has been an increase in the rate of those receiving nonsurgical treatments to maintain their function and quality of life. However, various problems, such as poor tolerance to chemoradiotherapy-related toxicity, are of greater concern in elderly adults than in younger individuals. In this review, we describe adverse events that should be particularly noted in elderly patients and provide an overview of countermeasures in nonsurgical treatments. We mainly focus on cisplatin-based chemoradiotherapy-the primary treatment for head and neck squamous cell carcinoma (HNSCC). Furthermore, we review the molecular targeted drugs and immune checkpoint inhibitors for elderly patients with HNSCC. Although the number of older patients is increasing worldwide, clinical trials aimed at determining the standard of care typically enroll younger or well-conditioned elderly patients. There is still very little evidence for treating elderly HNSCC older patients, and the question of optimal treatment needs to be explored.

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.

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.

Efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck cancer.

OBJECTIVE: We investigated the efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck cancer, as an alternative to cisplatin and 5-fluorouracil. METHODS: A total of 31 patients were enrolled in this study. S-1 was administered orally twice a day for 14 days followed by a 2-week rest. Nedaplatin was intravenously administered on day 4. If possible, two courses of chemotherapy were performed. The radiotherapy was started concurrently with the administration of S-1. RESULTS: The overall complete response rate was 81%. The 2-year overall survival rate was 96%. The 2-year relapse-free survival rate was 94%. The main adverse events were hematological toxicity, mucositis and dermatitis. CONCLUSIONS: Our findings suggest that this therapeutic regimen has either an equal or lower toxicity than the conventional cisplatin and 5-fluorouracil, and that it has equal efficacy with regard to the clinical response and short-term outcome. Moreover, it is possible to successfully perform this treatment in an outpatient setting.

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.