Lymph node metastasis (LNM) is a strong prognostic factor in many solid cancers, including head and neck squamous cell carcinomas (HNSCC), and LNM can be dependent upon primary tumor biology, as well as tumor dimension. Here, we investigate the relative risk of LNM in accordance to tumor dimension and biology in HNSCC subsites.
Materials and Methods
Medical data of 295 HNSCC patients who had undergone the initial curative surgery (oral tongue 174, oropharynx 75, hypopharynx 46) were analyzed to identify the significant predictive factor for LNM. Tumor volume and thickness were set as tumor dimensional variables, and biological variables included lymphovascular, perineural invasion, and tumor differentiation. Statistical analyses were conducted to assess the predictability of LNM from variables, and subgroup analyses according to the tumor subsites. In addition, we evaluated the impacts of tumor dimension and biological variables on the treatment outcomes and survival in HNSCC subsites.
The overall tumor dimension and biological variables had a similar impact on the prediction of LNM in HNSCC (area under the curve, 0.7682 and 0.7717). The prediction sensitivity of LNM in oral tongue cancer was mainly dependent on tumor dimension, while LNM in oroand hypo-pharynx cancers was more influenced by biological factors. Survival analyses also confirmed that biological factor was more powerful in estimating disease-free survival of hypopharyngeal cancer patients, while tumor dimension was more significant in that of oral cancer patients.
Tumor dimension and biology have a significant, tumor subsite-dependent impact on the occurrence of LNM and disease-free survival in HNSCC.
Lymphatic metastasis; Head and neck neoplasms; Tumor burden; Tumor biological markers; Neoplasm metastasis
Lymph node metastasis (LNM) in many solid cancers is a well-known prognostic factor; however, it has been debated whether regional LNM simply reflects tumor aggressiveness or is a source for further tumor dissemination. Similarly, the metastatic process in head and neck cancer (HNC) has not been fully evaluated. Thus, we aimed to investigate the relative significance of LNM in metastatic cascade of HNC using functional imaging of HNC patients and molecular imaging in in vivo models. First, we analyzed 18Fluorodeoxyglucose positron emission tomography (PET) parameters of 117 patients with oral cancer. The primary tumor and nodal PET parameters were measured separately, and survival analyses were conducted on the basis of clinical and PET variables to identify significant prognostic factors. In multivariate analyses, we found that only the metastatic node PET values were significant. Next, we compared the relative frequency of lung metastasis in primary ear tumors versus lymph node (LN) tumors, and we tested the rate of lung metastasis in another animal model, in which each animal had both primary and LN tumors that were expressing different colors. As a result, LN tumors showed higher frequencies of lung metastasis compared to orthotopic primary tumors. In color-matched comparisons, the relative contribution to lung metastasis was higher in LN tumors than in primary tumors, although both primary and LN tumors caused lung metastases. In summary, tumors growing in the LN microenvironment spread to systemic sites more commonly than primary tumors in HNC, suggesting that the adequate management of LNM can reduce further systemic metastasis.
Advancements in medical endoscopy and techniques of rigid bronchoscopy for foreign body removal have enabled higher diagnostic accuracy, reduced morbidity and precise manipulation. However, in pediatric patients, endoscope-combined forceps may be too big to fit into the small sized airway. Here we present our method of endoscope assisted rigid bronchoscopy in pediatric patients and compare the clinical benefits with conventional naked-eye rigid bronchoscopy.
We used a 2.7 mm, 0° straight endoscope and small caliber grasping forceps with 3.0 to 4.5 mm sized rigid bronchoscopy for very young (<3 years of age) patients of foreign body aspiration. As an assistant held the rigid bronchoscope in situ, the operator could manipulate the endoscope and forceps bimanually. With endoscopic guidance, the foreign body retrieval was performed carefully. The clinical advantages were compared between our endoscope-assisted method (n=29) and the conventional bronchoscopy method (n=33) in terms of operation time and recovery (hospital stay).
Bimanual endoscope-assisted rigid bronchoscopy method was technically feasible and safe. The operation time was less, compared to the conventional technique and the patients recovered more quickly. In all cases, our method completely removed the foreign body without need of a second bronchoscopy procedure.
Bimanual endoscope-assisted retrieval of airway foreign body in very young age pediatric patients was superior to the conventional naked-eye method concerning accurate manipulation and safety.
Bronchoscopy; Endoscopes; Foreign bodies; Airway obstruction; Preschool child
Primary squamous cell carcinomas arising from the thyroid gland (SCCTh) is extremely rare diseases, which have never been fully studied. Thus, we performed a systematic review and individual participant data meta-analysis of published SCCTh cases, to understand the clinical characteristics and to identify the prognostic factors of primary SCCTh. A literature search was conducted within Medline, EMBASE, Cochrane library databases and KoreaMed using the following Medical Subject Headings (MeSH) keywords: “primary,” “squamous,” “carcinoma,” “cancer,” and “thyroid.” Eighty-four patients' individual data from 39 articles and five patients' data in our institute were selected for analysis (N = 89). The mean age at diagnosis was 63.0 years (range, 24–90) and female preponderance (M:F = 1:2) was noted. The commonest complaint was the anterior neck mass, followed by dyspnea or dysphagia, and extension to the adjacent structure was found in 72%. The median survival was 9.0 months (95% CI, 6.0–23.0) and 3-year survival rate (3YSR) was 37.6% by Kaplan–Meier method, but only 20.1% by a shared frailty model for adjusting heterogeneity. Complete resection (R0) of tumors was the only significant prognostic factor in multivariable analysis, and the benefit of adjuvant treatment was not proved. The prognosis of patients with SCCTh is very poor (20% in 3YSR), but complete resection of disease is correlated with improved survival. To achieve complete surgical eradication of tumors, early detection and accurate diagnosis should be emphasized.
Diagnosis; outcomes; squamous cell carcinomas; thyroid gland; treatment
To introduce a new injection material for vocal fold diseases, which could be readily translated to clinical practice, we investigated the effectiveness of platelet-rich plasma (PRP) injection on the injured vocal fold in terms of histological recovery.
Blood samples were drawn from New Zealand White rabbits and PRP was isolated through centrifugation and separation of the samples. Using a CO2 laser, we made a linear wound in the 24 vocal fold sides of 12 rabbits and injected each wound with PRP on one vocal fold side and normal saline (NS) on the other. Morphologic analyses were conducted at 2, 4, and 12 weeks after injection, and inflammatory response, collagen deposit, and changes in growth factors were assessed using H&E and masson trichrome (MT) staining and western blot assay.
PRP was prepared in approximately 40 minutes. The mean platelet concentration was 1,315,000 platelets/mm3. In morphological analyses, decreased granulation was observed in the PRP-injected vocal folds (P<0.05). However, the irregular surface and atrophic change were not difference. Histological findings revealed significant inflammation and collagen deposition in NS-injected vocal folds, whereas the PRP-injected vocal folds exhibited less (P<0.05). However, the inflammatory reaction and fibrosis were not difference. In western blot assay, increased amounts of growth factors were observed in PRP-injected vocal folds.
Injection of injured rabbit vocal folds with PRP led to improved wound healing and fewer signs of scarring as demonstrated by decreased inflammation and collagen deposition. The increased vocal fold regeneration may be due to the growth factors associated with PRP.
Vocal fold; Scar; Wound healing; Growth factor; Platelet-rich plasma
To overcome the potential disadvantages of the use of foreign materials and autologous fat or collagen, we introduce here an autologous plasma gel for injection laryngoplasty. The purpose of this study was to present a new injection material, a plasma gel, and to discuss its clinical effectiveness.
Materials and Methods
From 2 mL of blood, the platelet poor serum layer was collected and heated at 100℃ for 12 min to form a plasma gel. The plasma gel was then injected into a targeted site; the safety and efficacy thereof were evaluated in 30 rats. We also conducted a phase I/II clinical study of plasma gel injection laryngoplasty in 11 unilateral vocal fold paralysis patients.
The plasma gel was semi-solid and an easily injectable material. Of note, plasma gel maintains the same consistency for up to 1 year in a sealed bottle. However, exposure to room air causes the plasma gel to disappear within 1 month. In our animal study, the autologous plasma gel remained in situ for 6 months in animals with minimal inflammation. Clinical study showed that vocal cord palsy was well compensated for with the plasma gel in all patients at two months after injection with no significant complications. Jitter, shimmer, maximum, maximum phonation time (MPT) and mean voice handicap index (VHI) also improved significantly after plasma gel injection. However, because the injected plasma gel was gradually absorbed, 6 patients needed another injection, while the gel remained in place in 2 patients.
Injection laryngoplasty with autologous plasma gel may be a useful and safe treatment option for temporary vocal cord palsy.
Plasma gel; injection; vocal cord palsy; laryngoplasty; acoustical analysis
The aim of this study was to assess the clinical role of 18F-FDG PET/CT for the evaluation of lymph node metastasis in periorbital malignancies, compared with CT alone.
Materials and Methods
We analyzed eighteen PET/CT and CT scans in 15 patients with biopsy-proven periorbital malignancies. We compared the diagnostic capabilities of PET/CT and CT with regard to nodal metastasis by level-by-level analysis and by N staging prediction. The reference standards were surgical pathology (n = 7) from dissected lymph node specimens and the results from radiological follow-up (n = 11, mean 20.5 months; range 10-52 months). Moreover, any changes in patient care as prompted by PET/CT were recorded and compared with treatment planning for CT alone.
PET/CT had a sensitivity of 100%, while CT had a sensitivity of 57% (p = 0.03) for nodal metastasis by level-by-level analysis. PET/CT had a specificity of 97%, positive predictive value of 93%, negative predictive value of 100%, and diagnostic accuracy of 98%, while the CT values for these same parameters were 97%, 89%, 82%, and 84%, respectively. PET/CT correctly predicted N staging with an accuracy of 100%, while CT was only 83% accurate (p = 0.01). Regarding the impact on patient care, the extent of surgery for regional lymph nodes and the treatment decision were modified by PET/CT in 39% of patients.
PET/CT could provide useful information in the management of regional lymph node metastases in patients with periorbital malignancies.
18F-FDG; PET/CT; Computed tomography (CT) scans; Lymphatic Metastasis; Eyelid Neoplasm
Salivary duct carcinoma (SDC) is a highly aggressive subtype of salivary gland cancers and there is no established standard therapy for this disease. Thus, development of molecular markers for SDC will be important to guide the diagnosis and therapy of this aggressive tumor.
We performed next-generation sequencing using the Ion Torrent AmpliSeq cancer panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes, and we analyzed copy number variations (CNVs) of 21 genes by NanoString nCounter for 37 patients with SDC. Fluorescent in situ hybridization was also conducted to confirm ERBB2 gene amplification. Clinical records and tumor histopathology of the patients were retrospectively reviewed.
Genetic alterations were detected in 29 of 37 (78.3%) tumors, including mutations in PIK3CA (N = 9, 24.3%), ERBB2 (N = 4, 10.8%), and EGFR (N = 4, 10.8%). To our knowledge, this is the first time that ERBB2 mutations have been reported in this tumor type. Both PIK3CA and ERBB2 mutation status were associated with poor overall survival, but without statistical significance. ERBB2 amplification was strong and common in SDC and almost all cases also exhibited EGFR and ERBB3 amplifications.
This study reports the largest and most comprehensive analysis of DNA aberrations in SDC. Our results show that PIK3CA and/or ERBB2 alterations in the development of SDC might be a useful diagnostic tool and could serve as a potential therapeutic target.
Salivary duct carcinoma; Next-generation sequencing; Molecular markers; PIK3CA; ERBB2; EGFR
Spontaneous regression of a malignant tumor is the phenomenon of disappearance of cancer cells without any treatments and it can be induced by an enhanced tumor-targeting immune response. However, there has not been a comprehensive immunological overview to compare the tumor-regressed lymph nodes and metastatic lymph nodes in the same patient.
We conducted a histologic analysis of various immune cells in an Asian female patient with buccal cancer (squamous cell carcinomas), in which the spontaneous regression of metastatic lymphadenopathy was confirmed by surgical pathology. The immune cell profiles between the metastatic nodes and the tumor-regressed nodes were compared. Tumor regression was confirmed by hematoxylin & eosin and cytokeratin/Ki-67 staining. Distinct differences were observed in Foxp3(+) regulatory T (Treg) cells and CD56(+) natural killer (NK) cells; a higher density of Foxp3(+) Treg cells was found in metastatic lymph nodes and more infiltration of CD56(+) NK cells in tumor regressed lymph nodes. Other immune cell populations (CD4, CD8, CD20, CD68, CD86, CD123, CD11c, and mannose receptor) showed no discernible differences in marker expression in the nodes examined.
Less recruitment of Treg and high infiltration of NK cells were key features in tumor-regressed lymph nodes. Modulation of Treg or NK cells may be a good therapeutic method to control lymph node metastasis.
Neoplasms; Lymph nodes; Lymphatic metastasis; Spontaneous neoplasm regression; Cellular immunity
The authors would report the results of definitive radiation therapy (RT) for early glottic cancer by two different radiation dose schedules.
From February of 1995 till June of 2008, 157 patients with T1-2N0 glottic cancer were treated with curative RT at Samsung Medical Center. All patients had squamous cell carcinoma, and there were 89 patients (56.7%) with T1a, 36 (22.9%) with T1b, and 32 (20.4%) with T2. Two different radiation dose schedules were used: 70 Gy in 35 fractions to 64 patients (40.8%, group A); and 67.5 Gy in 30 fractions to 93 patients (59.2%, group B). The median treatment durations were 50 days (range, 44 to 59 days) and 44 days (range, 40 to 67 days) in the groups A and B, respectively.
The median follow-up durations were 85 and 45 months for the groups A and B. No severe late complication of RTOG grade 3 or higher was observed, and there was no difference in acute or chronic complication between the groups. Twenty-four patients experienced treatment failure: local recurrence only in 19 patients; regional recurrence only in one; combined local and regional recurrence in four; and systemic metastasis in none. The overall 5-year disease-free survival and disease-specific survival rates were 84.7% and 94.8%. The disease-free survival rate in the group B was better (78.3% vs. 90.8%, P=0.031). This difference was significant only in T1 stage (83.4% vs. 94.6%, P=0.025), but not in T2 (62.7% vs. 60.6%, P=0.965). Univariate analysis showed that the tumor extent, cord mobility, T-stage, and the dose schedule had significant influence on the disease-free survival, and multivariate analysis showed that only the tumor extent and the dose schedule were associated with the disease-free survival.
Superior disease-free survival could be achieved by 2.25 Gy per fraction without increased toxicity over shorter RT duration, when compared with 2.0 Gy per fraction.
Laryngeal neoplasms; Radiotherapy; Dose fractionation
This is to report treatment results of major salivary gland cancer by surgery with or without postoperative radiation therapy (PORT).
Between March 1995 and January 2006, 94 patients with primary major salivary cancer underwent curative surgical resection at Samsung Medical Center. The parotid gland was the most commonly involved (73, 77.7%), followed by the submandibular and the sublingual. Neck dissection was added in 28 patients, and PORT was individually recommended to those with risk factors. Seventy-five (79.8%) patients received PORT. PORT volume included primary tumor bed and pathologically involved regional lymphatics, and no additional effort was made for elective nodal irradiation. The median total doses were 56.0 Gy to primary site and 58.7 Gy to regional lymphatics.
After median follow-up of 49 months, 21 patients had relapsed: 20 in PORT; and one in surgery alone group. As the first site of failure, distant metastasis was the most common (17 patients). Local recurrence occurred in three, and regional relapse in one. The lung was the most common site (10 patients), followed by the bone, and the brain. Five-yr disease free survival (DFS), local control, and overall survival (OS) rates were 74.4% and 94.7%, 96.0% and 100%, and 78.2% and 100% in PORT and surgery alone groups, respectively. On multivariate analysis, DFS was significantly affected by pN+ (hazard ratio [HR], 3.624; P=0.0319), while OS was by pN+ (HR, 7.138; P=0.0034) and perineural invasion (HR, 5.073; P=0.0187).
Based on our experience, the patients with early stage major salivary gland cancer with low risk can be effectively treated by surgery alone, and those who with risk factors can achieve excellent local and regional control by adding PORT. Omitting elective neck irradiation in patients with N0 disease seems a feasible strategy under accurate clinical evaluation. An effort is needed to decrease distant metastasis through further clinical trials.
Salivary gland cancer; Postoperative radiation therapy; Elective neck irradiation; Local control; Distant metastasis
The primary aim of this study was to determine whether 18F-FDG-PET/CT (PET/CT) scans provide additional diagnostic information in addition to the direct laryngoscopic examination (L/E) and contrast-enhanced CT (CT) in patients with glottic cancer during the initial evaluation.
Fifty-five consecutive patients with glottic cancer of the larynx that had L/E, CT and PET/CT were enrolled. The diagnostic value of each modality was compared for their accuracy in predicting the extent of the primary tumors on sub-site based analysis and the final tumor staging. The reference standards were either the surgical pathology findings or clinical/radiological follow-up outcome. Changes in patient care based on PET/CT results were compared with the treatment decisions based on L/E with CT.
For primary tumor sub-site based analysis, the sensitivity was significantly higher for L/E (92.8%) than for PET/CT (79.4%, P=0.028). The comparisons between L/E vs. CT and CT vs. PET/CT did not reach statistical significance. As an initial tumor-staging method the L/E had a diagnostic accuracy of 76.4%, compared to 61.8% for CT and 41.8% for PET/CT. The L/E and CT were better than the PET/CT (P=0.0009 and 0.049) for the initial TNM staging. PET/CT scanning changed the clinical decision-making based on the L/E with CT results in 12.7% of cases, of whom 5.5% had no additional PET/CT related benefit.
The results of this study showed that PET/CT imaging added no clinical information benefit compared to the L/E and CT for the initial evaluation of patients with glottic cancer.
Positron emission tomography; Tomography; X-ray computed; Laryngoscopy; Laryngeal neoplasms; Glottis
The objective of this study was to evaluate the feasibility of sentinel lymph node biopsy by using a radiotracer lymphatic mapping technique in patients with squamous cell carcinoma of the oral cavity, and the diagnostic value of this technique. We studied twenty patients with previously untreated squamous cell carcinomas of the oral cavity and N0 necks. After the peritumoral injection of 99mTc filtered tin colloid preop-eratively, lymphoscintigraphy and intraoperative mapping using a gamma detector were performed to localize sentinel nodes. An open biopsy of the sentinel node was followed by complete neck dissection. We identified the sentinel nodes in 19 of 20 patients (95.0%) by lymphoscintigraphy and in all (100%) by intraoperative gamma detector. In all cases, the status of the sentinel node accurately predicted the pathologic status of the neck with the false negative rate being 0%. The negative predictive value for the absence of cervical metastases was 100%. In conclusion, our radio-localization technique of sentinel nodes using 99mTc filtered tin colloid in N0 squamous cell carcinomas of the oral cavity is technically feasible and appears to accurately predict the presence of the occult metastatic disease.
Sentinel Lymph Node Biopsy; Lymphatic Metastasis; Mouth Neoplasms; Radionuclide Imaging