A Potential Radiomics-Clinical Model for Predicting Failure of Lymph Node Control after Definite Radiotherapy in Locally Advanced Head and Neck Cancer.

Background and Objectives: To optimally predict lymph node (LN) failure after definite radiotherapy (RT) in head and neck cancer (HNC) with LN metastases, this study examined radiomics models extracted from CT images of different periods during RT. Materials and Methods: This study retrospectively collected radiologic and clinical information from patients undergoing definite RT over 60 Gy for HNC with LN metastases from January 2010 to August 2021. The same largest LNs in each patient from the initial simulation CT (CTpre) and the following simulation CT (CTmid) at approximately 40 Gy were indicated as regions of interest. LN failure was defined as residual or recurrent LN within 3 years after the end of RT. After the radiomics features were extracted, the radiomics alone model and the radiomics plus clinical parameters model from the set of CTpre and CTmid were compared. The LASSO method was applied to select features associated with LN failure. Results: Among 66 patients, 17 LN failures were observed. In the radiomics alone model, CTpre and CTmid had similar mean accuracies (0.681 and 0.697, respectively) and mean areas under the curve (AUC) (0.521 and 0.568, respectively). Radiomics features of spherical disproportion, size zone variance, and log minimum 2 were selected for CTpre plus clinical parameters. Volume, energy, homogeneity, and log minimum 1 were selected for CTmid plus clinical parameters. Clinical parameters including smoking, T-stage, ECE, and regression rate of LN were important for both CTpre and CTmid. In the radiomics plus clinical parameters models, the mean accuracy and mean AUC of CTmid (0.790 and 0.662, respectively) were more improved than those of CTpre (0.731 and 0.582, respectively). Conclusions: Both models using CTpre and CTmid were improved by adding clinical parameters. The radiomics model using CTmid plus clinical parameters was the best in predicting LN failure in our preliminary analyses.

Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery.

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.

A new histopathological location of parathyroid gland with high possibility of unintended parathyroidectomy.

Background: Unintended parathyroidectomy occasionally happens despite meticulous capsular dissection and the histopathological location of removed parathyroid glands were traditionally classified as extracapsular, subcapsular, and intrathyroidal location. This study aimed to investigate the new histopathological location of parathyroid gland with high possibility of unintended parathyroidectomy that was difficult to be found with naked eye despite capsular dissection. Methods: This study investigated unintended parathyroidectomy that occurred in 743 patients who received thyroid surgery by reviewing pathology reports and slides. The histopathological location of unintentionally removed parathyroid glands was classified as intracapsule and extracapsule, and the intracapsular glands were further classified as completely buried in the thyroid parenchyme, partially buried, and subcapsular locations. Results: The incidence of unintended parathyroidectomy was 12.8%. Among the 103 unintentionally removed parathyroid glands, 74 (71.8%) were found intracapsular and 29 were extracapsular. Among the intracapsular glands, 57 (55.4%) parathyroid glands were found in difficult locations such as completely buried (40.8%) and partially buried (14.6%). Conclusions: The partially buried parathyroid gland can act as a risk factor for unintended parathyroidectomy comparable to intrathyroidal parathyroid gland despite the surgeon's best effort with meticulous capsular dissection. However, continued advances in visualizing technique such as autofluorescence imaging may lower the chance of incidentally removed partially buried parathyroid glands in the future.

The Utility of Gastrointestinal Endoscopic Examination Versus Positron Emission Tomography-Computed Tomography in the Detection of Second Primary Lesions in Korean Patients With Head and Neck Cancer.

OBJECTIVE: Head and neck cancer often accompany a synchronous secondary primary lesion in the digestive tract. The aim of this study was to compare detection rates between positron emission tomography-computed tomography (PET-CT) and esophagogastroduodenoscopy (G-fiber) or colonoscopy (C-fiber) in the initial staging and to analyze risk factors for premalignant, malignant, and total synchronous secondary primary lesions. METHODS: A total of 739 patients with head and neck cancer who underwent PET-CT, G-fiber, or C-fiber were analyzed retrospectively. RESULTS: Positron emission tomography-CT did not definitely detect any premalignant synchronous secondary primary lesions (0 [0%] of 739) but definitely detected 10 malignant synchronous secondary primary lesions (10 [1.35%] of 739). Esophagogastroduodenoscopy or C-fiber detected all 20 premalignant synchronous secondary primary lesions (20 [2.71%] of 739) and all 37 malignant synchronous secondary primary lesions (37 [5.00%] of 739). The patients with nasopharynx cancer tended to have premalignant synchronous secondary primary lesions (odds ratio [OR]: 3.793; 95% CI: 1.414-10.171; P = .008). Those with distant metastasis tended to have premalignant (OR: 4.743; 95% CI: 1.508-14.916; P = .009), malignant (OR: 3.803; 95% CI: 1.486-9.731; P = .005), and total synchronous secondary primary lesions (OR: 2.753; 95% CI: 1.159-6.538; P = .022). CONCLUSIONS: Premalignant or malignant synchronous secondary primary lesions that were not definitely detected by PET-CT could be found in the endoscopic examination.

Generation of induced pluripotent stem cell line (KRIBBi004-A) from adult bone marrow CD34+ cells from a patient carrying 46,XX,t(1;5)(p31.1;35.1) karyotype.

Induced pluripotent stem cell (iPS) technology may be advantageous for the study of genetic aberrations in terms of recapitulating the full manifestation of pathological features in vitro, identifying underlying pathways, and developing personalized therapeutics rather than procuring somatic cells from patients. Here, we derived an iPSC line from a patient with reciprocal chromosome translocation, t(1;5)(p31.1;35.1), as a novel alternative model to identify clinical phenotypes induced by genetic instability. The resulting iPSC line generated from somatic cells with an existing instability showed representative characteristics of PSCs, and might serve as an unparalleled cellular resource for the development of a custom remedy.

ß2-adrenergic receptor expression and the effects of norepinephrine and propranolol on various head and neck cancer subtypes.

The present study aimed to investigate expression of ß2-adrenergic receptor (AR), the effect of the stress-related neurotransmitter norepinephrine (NE) on cell viability, proliferation and the therapeutic effect of propranolol, which is a typical ß-blocker in various type of head and neck cancers for the first time. The ß2-AR expression was investigated using immunohistochemistry and an immunoreactive scoring (IRS) system in 57 different head and neck cancer specimens, and reverse transcriptase-polymerase chain reaction and western blotting in four head and neck cancer cell lines (HNCCLs). Cell viability and proliferation assays were performed using 0, 1, 5 and 10 µM of NE and 1 µM of propranolol in four HNCCLs. The expression of ß2-AR was positive in the majority of head and neck cancer tissues (55/57, 96.5%); however, it was significantly higher in oral cavity cancer than in pharyngeal cancer (median IRS: 9 vs. 3; P<0.001). All HNCCLs exhibited ß2-AR expression, with a higher expression level detected in the oral cavity cancer cell line than in the others. NE stimulated viability (oral cavity, 206%; larynx, 156%; pharynx, 130%; nasal cavity, 137%; 10 µM NE) and proliferation (124, 176, 131 and 127%, respectively) in a dose-dependent manner in all HNCCLs. Conversely, propranolol attenuated such viability (55, 42, 18 and 22%, respectively) and proliferation (22, 40, 61 and 48%, respectively). In conclusion, the viability and proliferation of various head and neck cancers may be directly stimulated by stress and this may be attenuated by ß-blockers.

Effects of N-acetylcysteine inhalation therapy on the quality of life of patients with head and neck cancer who are receiving radiation therapy: a prospective non-randomized controlled multi-center study.

BACKGROUNDS AND PURPOSE: Radiation therapy is an important mode of treatment for patients with head and neck cancers, but some associated complications can reduce the quality of life. We investigated whether N-acetylcysteine inhalation therapy improved the quality of life of such patients. MATERIALS AND METHODS: We designed a prospective, non-randomized controlled multi-center study involving 10 institutions. We enrolled 120 patients (80 in the experimental group and 40 in the control group). Patients in the experimental group inhaled nebulized liquid N-acetylcysteine (2400 mg daily) for 8 weeks from the start of radiation therapy. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N 35. RESULTS: N-acetylcysteine inhalation was not associated with any side effect or discomfort. The reduction in painkiller use from the end of N-acetylcysteine inhalation therapy to the 1-month follow-up was greater in the experimental group than in the control group (P = 0.014). Dry mouth symptoms also improved significantly in the experimental group (P = 0.019). CONCLUSION: N-acetylcysteine inhalation improves the quality of life of patients with head and neck cancers who are receiving radiation therapy, without any specific side effect.

Biomimetic Gold Nanoshell-Loaded Macrophage for Photothermal Biomedicine.

The purpose of this study was to investigate the effect of photothermal treatment (PTT) with gold nanoshell (ANS) using a macrophage-mediated delivery system in a head and neck squamous cell carcinoma (HNSCC) cell line. To achieve this, ANS-loaded rat macrophages (ANS-MAs) were prepared via the coculture method with ANS. The human HNSCC (FaDu cell) and macrophage (rat macrophage; NR8383 cell) hybrid spheroid models were generated by the centrifugation method to determine the possibility of using ANS-MAs as a cancer therapy. These ANS-MAs were set into the tumor and macrophage hybrid spheroid model to measure PTT efficacy. Kinetic analysis of the spheroid growth pattern revealed that this PTT process caused a decreasing pattern in the volume of the hybrid model containing ANS-MAs (p < 0.001). Comparison with empty macrophages showed harmony between ANS and laser irradiation for the generation of PTT. An annexin V/dead cell marker assay indicated that the PTT-treated hybrid model induced increasing apoptosis and dead cells. Further studies on the toxicity of ANS-MAs are needed to reveal whether it can be considered biocompatible. In summary, the ANS was prepared with a macrophage as the delivery method and protective carrier. The ANS was successfully localized to the macrophages, and their photoabsorption property was stationary. This strategy showed significant growth inhibition of the tumor and macrophage spheroid model under NIR laser irradiation. In vivo toxicology results suggest that ANS-MA is a promising candidate for a biocompatible strategy to overcome the limitations of fabricated nanomaterials. This ANS-MA delivery and PTT strategy may potentially lead to improvements in the quality of life of patients with HNSCC by providing a biocompatible, minimally invasive modality for cancer treatment.

The Outcome of Early Ablative Fractional Laser Treatment for Thyroidectomy Scars.

BACKGROUND AND OBJECTIVES: Ablative fractional laser (AFL) systems are commonly used to treat various scars, and recent research has indicated that early treatment with AFL may have a preventive effect on scars. This study was designed to evaluate the efficacy of early treatment with a 10,600 nm carbon dioxide (CO2 ) AFL on thyroidectomy scars and compare it to late (conventional) treatment for the same and untreated controls. STUDY DESIGN/MATERIALS AND METHODS: We performed a prospective, evaluator-blinded, split-scar study on fresh thyroidectomy scars between July 2014 and July 2017. Scars were divided into two equal portions. Early AFL treatment had begun 1 month after surgery; five sessions on the right half of the scar was performed at 1-month intervals. Late AFL treatment followed for 1 month after the final early treatment session on the left half of the scar at the same interval. The scars were evaluated at 6 and 11 months postoperatively using scar analysis scales and patient questionnaires. RESULTS: Twenty-four out of 28 patients completed the study. The mean decrease in Vancouver Scar Scale (VSS) scores was significantly higher for the early treated right halves of the scars both at the 6th month (vs. untreated controls) and at the 11th month (vs. late treated controls). The VSS subset analysis showed that the early treated sides had significantly greater improvement in pliability and height than the control sides at each point of evaluation. CONCLUSIONS: Early postoperative AFL treatment is safe and effective in improving linear surgical scars, such as thyroidectomy scars, and may be a promising option for scar prevention. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Assessment of Chronological Volume Changes in Radial Forearm Free Flaps for Tongue Cancer.

OBJECTIVE: The radial forearm free flap (RFFF) is a commonly used free flap for tongue cancer. Postoperative changes in the volume of free flap are known to influence the functional restoration of the resected tongue. This study aimed to estimate chronological volume changes in RFFFs for tongue cancer and to determine the clinical factors affecting these changes. METHODS: Clinical data for 19 patients who underwent RFFF reconstruction for tongue cancer between May 2004 and September 2013 were retrospectively reviewed. The flap volume was measured 3, 6, 12, 24, and 36 months after surgery using CT and the Picture Archiving and Communication System software. RESULTS: Relative to volumes at 3 months, median flap volumes decreased to 98.55, 70.16, 62.86, and 58.84% at 6, 12, 24, and 36 months, respectively. None of the evaluated parameters were correlated with volume changes. CONCLUSIONS: Over time, the volume of RFFF in the tongue decreased. Considering this, free flap reconstruction should be carried out in tongue cancer surgery.

Objective Assessment of Postoperative Swallowing Difficulty Through Ultrasound in Patients Undergoing Thyroidectomy.

Swallowing discomfort is a common postoperative complaint in patients undergoing thyroidectomy. Contraction of the strap muscles might cause resistance to elevation of the laryngotracheal unit, and downward movement of the laryngotracheal unit may lead to swallowing discomfort. However, few studies have evaluated the mechanism related to limited laryngotracheal elevation after thyroidectomy. We aimed to objectively verify the presence of postoperative impaired laryngotracheal elevation through ultrasound evaluation in patients undergoing thyroidectomy and evaluate its relationship with limitation of laryngotracheal elevation. This is a prospective clinical study. Among patients undergoing hemithyroidectomy and total thyroidectomy, the patients who were followed up for ≥ 6 months were selected (N = 40). Ultrasound evaluation was done preoperatively and at 1, 3, and 6 months postoperatively. Laryngotracheal movement was recorded and the length of elevation was measured. Symptom after thyroidectomy was evaluated through swallowing-related items of thyroidectomy-related voice questionnaire. Ultrasound evaluation verified the presence of limited laryngotracheal elevation postoperatively in patients undergoing thyroidectomy. After thyroidectomy, the swallowing-related score was significantly increased, and was recovered time-dependently at 1 month. Laryngotracheal elevation showed significant decrease after thyroidectomy. The symptom score of swallowing was significantly correlated with the length of laryngotracheal elevation. Post-thyroidectomy ultrasound evaluation verified that laryngotracheal elevation was significantly impaired. Presence of adhesion between the laryngotracheal unit and the superficial soft tissue was the probable cause of the limitation at 6 months after thyroidectomy. The length of laryngotracheal elevation was related to the symptom score of swallowing after thyroid surgery.

Characteristics of residual lymph nodes after six months of antituberculous therapy in HIV-negative individuals with cervical tuberculous lymphadenitis.

BACKGROUND: The therapeutic response of cervical tuberculous lymphadenitis (CTBL) may be delayed or paradoxical, with the frequent development of residual lymph nodes (LNs) during and after antituberculous treatment. We investigated the incidence of residual LNs and the clinical, radiological, microbiological, and pathologic responses of patients with CTBL after 6 months of antituberculous therapy. METHODS: The medical records of HIV-negative adult patients with CTBL diagnosed between July 2009 and December 2017 were analyzed. After 6 months of first-line antituberculous treatment, computed tomography (CT) scans were conducted to evaluate for residual LNs. Fine-needle aspiration biopsy (FNAB) was carried out if a patient presented with residual LNs > 10 mm in diameter with central necrosis, peripheral rim enhancement, or perinodal inflammation on CT scan. RESULTS: Residual LNs were detected in 35 of 157 patients who underwent follow-up CT scans and were more commonly observed in younger patients who completed the treatment (mean years ± standard deviation [SD]: 33 ± 13 vs. 44 ± 16, p < 0.001). The recurrence rate was approximately 5%, which was not significantly different in both groups. Among the 15 patients who underwent FNAB, 3 (30%) presented with granuloma, and 2 of 15 and 10 of 14 patients had positive AFB and TB PCR results, respectively. The TB culture results of 15 patients were negative. CONCLUSIONS: Residual LNs may still be observed after 6 months of antituberculous treatment. Although the radiologic and pathologic findings after treatment are still indicative of TB, not all residual LNs indicate recurrence or treatment failure. A six-month therapy may be sufficient for cervical tuberculous lymphadenitis.

Anoctamin-1 affects the migration and invasion of anaplastic thyroid carcinoma cells.

Anaplastic thyroid carcinoma (ATC) is a rare malignancy with very poor prognosis. The exact cause underlying its strong aggressive nature is not clear. Here, we discovered the elevated expression of anoctamin-1 (ANO1; Ca2+-activated Cl- channels) in advanced-stage ATC tissue. Using different ATC cell lines, the degree of expression of ANO1 was found to be related to the degree of ATC cell invasion by quantitative reverse transcription polymerase chain reaction and western blotting. Suppression of ANO1 activity either by selective inhibitor (T16Ainh-A01) or by siRNA significantly attenuated the migration and invasion of ATC cells. In conclusion, ANO1 appears to increase the ability of ATC cells to invade and migrate. Our results also suggest that the expression of ANO1 in patients with ATC may be helpful in predicting the prognosis of ATC.

Clinical Analysis of Pediatric Thyroid Cancer: A Single Medical Institution Experience of 18 Years.

OBJECTIVE: The incidence of pediatric thyroid cancer is relatively low compared to the disease in adults. This study aims to present the data in our institution on pediatric thyroid cancer patients, with particular emphasis on the risk factors of recurrence together with treatment outcomes. SUBJECTS AND METHODS: Between January 2000 and July 2018, patients <20 years who were diagnosed with thyroid carcinoma and primarily treated with surgery at a major large-volume tertiary medical center specializing in thyroid cancer were enrolled. A total of 83 patients were eligible for this study. RESULTS: The majority of the studied patients were girls and adolescents (age ≥13 years). Papillary thyroid carcinoma (PTC) was the most common pathology (n = 74). PTC tumors >1 cm showed higher rate of lymph node metastasis and extrathyroidal extension than tumors ≤1 cm. All patients survived with nine PTC patients who displayed treatment failure. Age, tumor size, multifocality, lateral lymph node metastasis, and postoperative thyroglobulin levels were significant prognosticators for disease recurrence. CONCLUSION: Pediatric thyroid cancer is relatively rare and should be considered a specific disease entity with respect to the thyroid cancer in adults, since there are several distinctive characteristics.

Pre-diagnostic beta-blocker use and head- and neck cancer risk: A nationwide population-based case-control study.

ß-blockers have been reported to exhibit potential anticancer effects in various cancer studies. However, few clinical studies concerning head and neck cancer have been conducted. We hypothesized that ß-blockers could decrease the incidence of head and neck cancer. Therefore, we investigated the association between ß-blocker treatment and head and neck cancer incidence.Between January 2006 and December 2015, we selected 12,127 patients with head and neck cancer for this nationwide study using data from the Korean Health Insurance Review and Assessment Service. The patients were matched 1:5 with 60,635 control participants according to age, sex, and, region. Logistic regression analysis was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of cancer associated with ß-blocker treatment. In the analysis, a crude (simple), adjusted model (adjusted model for age, sex, income, region of residence, hypertension, diabetes, and hyperlipidemia) was used.The OR for head and neck cancer incidence was not lower in the ß-blocker cohort (OR: 1.18; 95% CI: 1.105-1.26), especially for the oral cavity (OR: 1.165; 95% CI: 1.013-1.340), hypopharynx (OR: 1.555; 95% CI: 1.232-1.963), nasopharynx (OR: 1.251; 95% CI: 1-1.564), and paranasal sinus (OR: 1.378; 95% CI: 1.027-1.849). The duration of ß-blocker use was not related to head and neck cancer incidence.This study did not provide evidence that ß-blockers can decrease the risk of head and neck cancer.

Guidelines for the Surgical Management of Oral Cancer: Korean Society of Thyroid-Head and Neck Surgery.

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to provide guidance on the implementation of a surgical treatment of oral cancer. MEDLINE databases were searched for articles on subjects related to "surgical management of oral cancer" published in English. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. The quality of evidence was rated with use RoBANS (Risk of Bias Assessment Tool for Nonrandomized Studies) and AMSTAR (A Measurement Tool to Assess the Methodological Quality of Systematic Reviews). Evidence-based recommendations for practice were ranked according to the American College of Physicians grading system. Additional directives are provided as expert opinions and Delphi questionnaire when insufficient evidence existed. The Committee developed 68 evidence-based recommendations in 34 categories intended to assist clinicians and patients and counselors, and health policy-makers. Proper surgical treatment selection for oral cancer, which is directed by patient- and subsite-specific factors, remains the greatest predictor of successful treatment outcomes. These guidelines are intended for use in conjunction with the individual patient's treatment goals.

Comparison of functional outcomes after total thyroidectomy and completion thyroidectomy: Hypoparathyroidism and postoperative complications.

OBJECTIVE: This study aimed to investigate differences in functional outcomes of postoperative complications and hypoparathyroidism between patients who underwent completion thyroidectomy (CT) after thyroid lobectomy or total thyroidectomy (TT) as an initial treatment. MATERIALS AND METHODS: We retrospectively analyzed the differences of functional outcomes after completion thyroidectomy and total thyroidectomy without lymph node dissection. We reviewed the medical records of 396 patients who underwent CT or TT for thyroid disease at Korea University Guro Hospital from March 2002 to August 2016. RESULTS: Of the 396 patients, 32 underwent CT and 364 underwent TT. There were 72 male patients and 324 female patients. Transient hypoparathyroidism was observed in 4 (9.4%) of the CT patients and 97 (26.6%) of the TT patients, with a statistically significant difference (p=0.031). Permanent hypoparathyroidism was observed in 1 patient (3.1%) in the CT group and in 13 patients (3.6%) in the TT group, which was not significantly different. There were no significant differences in the postoperative complication of temporary recurrent laryngeal nerve injury, wound infection, and hematoma between two patients group. CONCLUSION: The incidence of transient hypoparathyroidism in CT patients was significantly lower than in TT patients. These safety and functional superiority of CT should be considered when determining the scope and extent of operation in patients requiring surgery for thyroid disease.

Extranodal involvement of diffuse large B-cell lymphoma in the head and neck: An indicator of good prognosis.

OBJECTIVE: In this study, we analyzed clinicopathological characteristics and survival outcomes according to extranodal involvement of diffuse large B-cell lymphoma (DLBCL) in the head and neck. METHODS: A retrospective analysis was conducted on 110 patients from 2004 to 2014 with CD20-positive DLBCL involving the head and neck area. Patients were categorized into two groups, extranodal and nodal, according to involvement of extranodal sites in the head and neck. Outcome measurements for the groups included clinical response to treatment and recurrence rates. RESULTS: Palatine tonsils were the most frequently involved extranodal site in the head and neck (29.1%). Among clinicopathological parameters, proportion of patients with lactate dehydrogenase over 350 IU/L (p=0.033), cell of origin (p<0.001), and treatment outcomes (p=0.007) were significantly different between the two groups. Among cell origin markers CD10, Bcl6, and MUM1, MUM1 was significantly correlated with extranodal involvement (p=0.029). Recurrence rates were similar between groups, while disease-specific survival was significantly higher in the extranodal group (p=0.011). Disease-specific survival of the extranodal group was also higher than the nodal group with extranodal involvement of other body sites (p=0.010). Among patients with negative expression of CD10 (p=0.015), Bcl6 (p=0.018), and MUM1 (p=0.005), survival was longer in the extranodal than the nodal group. CONCLUSIONS: DLBCL patients with extranodal involvement of the head and neck may have longer survival outcomes than patients with solely nodal involvement. Increased survival may be more prominent in patients with negative expression of CD10, Bcl6, and MUM1.

Clinicopathological significance of cancer-associated fibroblasts in papillary thyroid carcinoma: a predictive marker of cervical lymph node metastasis.

PURPOSE: Most tumors have obvious biologically active fibroblasts known variously as myofibroblasts or cancer-associated fibroblasts (CAFs) in the stroma. CAFs have been known as an important factor of cancer invasion and metastasis. This study aimed to investigate the presence of CAFs in patients with papillary thyroid carcinoma (PTC) and evaluate the correlation between CAFs and cervical lymph node (LN) metastasis in PTC through immunohistochemistry. METHODS: The medical records of 128 patients who were diagnosed with PTC from January 1, 2010 to December 31, 2010 were reviewed, and 78 patients who underwent total thyroidectomy with or without neck dissection, were included in this study. A retrospective pathological evaluation was performed to verify the presence of CAFs. CD34 and α-smooth muscle actin (SMA) were used as markers of CAFs. RESULTS: Among 78 patients with PTC, 65 had desmoplastic stromal reaction around the PTC. Through immunohistochemical study of anti-CD34 and α-SMA antibodies, CAFs were found in 42 (64.6%) cases with desmoplastic stroma around the PTC. Univariate analysis showed that tumor size and CAFs were the risk factors of LN metastasis in patients with PTC, while multivariate analysis revealed that CAFs were the only independent risk factor of LN metastasis in patients with PTC. CONCLUSION: This study revealed the presence of CAFs in PTC. Furthermore, CAFs were found to be a risk factor of LN metastasis in PTC. Therefore, CAFs may be used as a predictive marker for LN metastasis in patients with PTC.

Low expression of CD40L in tumor-free lymph node of oral cavity cancer related with poor prognosis.

BACKGROUND: Recently, the genetic alterations associated with tumor progression and impaired host immunity against transformed cells draw increased attention. Here, we characterized the differential gene expression patterns and protein expression in tumor-free lymph node from recurrent and non-recurrent tumors to identify independent prognostic markers for oral squamous cell carcinoma (OSCC). METHODS: A cDNA microarray analysis was performed to identify the differentially expressed genes in regional tumor-free lymph nodes from OSCC patients with and without recurrence. Then, the protein expression of the selected genes was analyzed by immunohistochemistry in 60 OSCC patients to determine their association with survival. RESULTS: Widespread down-regulation of genes involved in antigen processing and recognition in lymph nodes was a distinctive feature. In univariate Kaplan-Meier analysis, lower expression of CD40L and CD80 in tumor-free lymph nodes was significantly correlated with poorer survival. In multivariate Cox regression analysis, CD40L was identified as an independent prognostic marker of disease-free survival. CONCLUSION: Our data indicate that impaired host immunity (decreased CD40L expression) along with the TNM staging might be an important factor determining the prognosis of OSCC.