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
The aim of this study was to compare a negative pressure drain with a natural drain in order to determine whether a negative pressure drainage tube causes an increase in the drainage volume.
Materials and Methods
Sixty-two patients who underwent total thyroidectomy for papillary thyroid carcinoma (PTC) were enrolled in the study between March 2010 and August 2010 at Gyeongsang National University Hospital. The patients were prospectively and randomly assigned to two groups, a negative pressure drainage group (n=32) and natural drainage group (n=30). Every 3 hours, the volume of drainage was checked in the two groups until the tube was removed.
The amount of drainage during the first 24 hours postoperatively was 41.68±3.93 mL in the negative drain group and 25.3±2.68 mL in the natural drain group (p<0.001). After 24 additional hours, the negative drain group was 35.19±4.26 mL and natural drain groups 21.53±2.90 mL (p<0.001). However, the drainage at postoperative day 3 was not statistically different between the two groups. In addition, the vocal cord palsy and temporary and permanent hypocalcemia were not different between the two groups.
These results indicate that a negative pressure drain may increase the amount of drainage during the first 24-48 hours postoperatively. Therefore, it is not necessary to place a closed suction drain when only a total thyroidectomy is done.
Total thyroidectomy; drainage; papillary thyroid carcinoma
Although human papillomavirus (HPV) infection is considered as a favorable prognostic factor in oropharyngeal cancer, the prognosis of HPV-associated tonsil cancer has rarely been studied especially when surgery was the main treatment. In this study, the authors investigated the effect of p16 over-expression (HPV infection) on tonsil cancer prognosis according to the type of treatment, HPV presence by PCR, and expression of p53 and epidermal growth factor receptor (EGFR) by immunohistochemistry (IHC).
Medical records of 33 tonsil cancer patients were reviewed. Using formalin-fixed and paraffin-embedded tumor specimens, PCR-based genotyping of HPV and IHC of p16, p53 and EGFR were performed. The effects of HPV presence and the expression of IHC markers were analyzed on the recurrence-free survival. Five-year disease-free survival (DFS) rates were evaluated according to p16 expression status.
An over-expression of p16 was observed in 27 (81.9%) out of 33 cases. Surgery-based treatment was provided for 21 (63.6%) patients. There was no association between p16 immunoreactivity and HPV presence, nor with p53 and EGFR expression. Regardless of main treatment modalities, five-year DFS did not differ by p16 expression status (P=0.051). However, over-expression of p16 was associated with a lower recurrence in multivariable analyses (P=0.046).
Regardless of main treatment modalities, an over-expression of p16 (HPV infection) is associated with a lower recurrence in tonsil cancers. However it is not associated with simple HPV presence or p53 and EGFR over-expression.
Human papillomavirus; Oropharyngeal neoplasms; Therapeutics; Immunohistochemistry; Prognosis; p16 (INK4A)
The aims of this study were to determine the benefits of short-term empirical proton pump inhibitor (PPI) medication on laryngopharyngeal reflux (LPR) and to determine whether scores on the reflux symptom index (RSI) and the reflux finding score (RFS) could be combined to identify subgroups of patients that will more likely to improve with this medication.
Fifty-one Korean Otolaryngology Board-certified specialists joined this prospective, multi-center, and open-label observational study. A total of 1,142 adult patients with LPR was enrolled for 12 weeks of rabeprazol medication. According to pre-treatment scores on RSI and RFS, patients were divided into 4 subgroups. RFS and RSI were measured repeatedly with a month interval along the treatment period. Changes of RSI and RFS were analyzed in an overall study cohort as well as in each subgroup.
Approximately 40% (n=455) of enrolled patients were followed up until 12 weeks of PPI treatment. Significant improvement in RSI was obtained in 29%, 58%, and 75% of patients after 4, 8, and 12 weeks of PPI medication. RFS was improved in 16%, 42%, and 57% of the patients with 4, 8, and 12 weeks of PPI medication. All subgroups showed improvement regardless of their pre-treatment scores on the RSI and RFS.
Even though RSI and RFS may be used as a general guideline for LPR management, pre-treatment RSI and RFS are not useful in predicting the patients' response to short-term PPI medication in the usual pattern of practice for LPR, which is mostly based on the physical evaluation and history taking.
Laryngopharyngeal reflux; Proton pump inhibitors; Rabeprazole; Short-term therapy; Predictors of response
High incidence of hypocalcemia after thyroidectomy is a major determinant in delay of discharge. Even though many studies have focused on the search for reliable early predictors of postoperative hypocalcemia, definitions of hypocalcemia are diverse; therefore, interpretation and application of previously reported findings may not be easy. We aimed to elucidate diverse patterns of post-thyroidectomy hypocalcemia and to provide reliable early predictors for these different types of hypocalcemia.
Retrospective chart review was performed and eligible 112 patients of thyroidectomy were categorized into four groups according to symptomatic and/or biochemical hypocalcemic criteria. A mismatch of occurrence and the timing of symptomatic or biochemical abnormalities were evaluated. Predictive values of commonly used biomarkers were compared in each group; levels of serum total calcium and ionized calcium, and intact parathyroid hormone (PTH).
Among 62 hypocalcemic patients, 45 patients (72.5%) experienced both symptomatic and biochemical abnormalities during hospitalization. A mismatch on the timing of initial detection of symptomatic and biochemical hypocalcemia was observed in 21 patients (46.6%). Intact PTH level measured at 1 hour was a useful indicator in prediction of symptomatic hypocalcemia with 79.7-87.4% of diagnostic accuracy. Serum ionized calcium measured next morning after surgery was a reliable predictor of biochemical hypocalcemia with 77.9-94.8% of diagnostic accuracy.
For the safety of patients, the possibility of both symptomatic and biochemical hypocalcemia should be considered together before deciding early discharge. Using intact PTH for symptomatic hypocalcemia and day-1 ionized serum calcium level for biochemical hypocalcemia will be helpful for the reliable prediction of heterogeneous nature of postoperative hypocalcemia.
Hypocalcemia; Parathyroid hormone; Thyroidectomy; Early diagnosis; Postoperative complicationns
These days, the main injection laryngoplasty technique is cricothyroid (CT) approach. However, patients who have previously undergone other neck treatments, such as thyroidectomy or neck dissection have distorted anatomical landmark makes this approach more difficult. The aim of this study is to determined the efficiency of transcartilaginous (TC) approah as compared with CT approach for unilateral vocal fold paralysis patients, especially for previously neck treated patients.
From March 2005 to February 2008, 137 consecutive injection laryngoplasties were performed in patients with unilateral glottic insufficiency. Percutaneous injection was performed under local anesthesia into the vocalis muscle, using disposable 25 G 4 cm long needles through the cricothyroid membrane or directly through the thyroid cartilage. Of the 137 patients, 124 completed acoustic, perceptual, stroboscopic, and subjective evaluations prior to the injection and at 3 months after the injection.
In the 124 patients, the CT and TC approaches were used in 94 and 30 patients, respectively. Acoustic and perceptual parameters (GRBAS, MPT, jitter, shimmer), voice handicap index, and grades of mucosal waves and glottic closure were significantly improved after the injection in both the CT and TC groups (P<0.05). Only two patients (6.6%) had penetration difficulties, because of ossification of the thyroid cartilage. The overall success rates of the CT and TC approaches were 86.2%, 93.3%, respectively. However, the success rate of the TC approach in patients who had previously undergone neck treatments was significantly higher than that of the CT approach (100% vs. 65% P<0.05).
Based on the preliminary results of this trial, injection laryngoplasty using a TC approach was an effective alternative to the CT approach, especially in patients who had previously undergone neck surgeries.
Injection laryngoplasty; Thyroid cartilage; Vocal cord paralysis
This paper investigates the effectiveness of measures related to vocal tract characteristics in classifying normal and pathological speech. Unlike conventional approaches that mainly focus on features related to the vocal source, vocal tract characteristics are examined to determine if interaction effects between vocal folds and the vocal tract can be used to detect pathological speech. Especially, this paper examines features related to formant frequencies to see if vocal tract characteristics are affected by the nature of the vocal fold-related pathology. To test this hypothesis, stationary fragments of vowel /aa/ produced by 223 normal subjects, 472 vocal fold polyp subjects, and 195 unilateral vocal cord paralysis subjects are analyzed. Based on the acoustic-articulatory relationships, phonation for pathological subjects is found to be associated with measures correlated with a raised tongue body or an advanced tongue root. Vocal tract-related features are also found to be statistically significant from the Kruskal-Wallis test in distinguishing normal and pathological speech. Classification results demonstrate that combining the formant measurements with vocal fold-related features results in improved performance in differentiating vocal pathologies including vocal polyps and unilateral vocal cord paralysis, which suggests that measures related to vocal tract characteristics may provide additional information in diagnosing vocal disorders.
To evaluate the prognostic value of volume-based metabolic parameters measured with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in patients with clinically node-negative (cN0) oral tongue squamous cell carcinoma (OTSCC) as compared with other prognostic factors.
Materials and Methods
In this study, we included a total of 57 patients who had been diagnosed with cN0 tongue cancer by radiologic, 18F-FDG PET/CT, and physical examinations. The maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors were measured with 18F-FDG PET. The prognostic significances of these parameters and other clinical variables were assessed by Cox proportional hazards regression analysis.
In the univariate analysis, pathological node (pN) stage, American Joint Committee on Cancer (AJCC) stage, SUVmax, SUVavg, MTV, and TLG were significant predictors for survival. On a multivariate analysis, pN stage (hazard ratio = 10.555, p = 0.049), AJCC stage (hazard ratio = 13.220, p = 0.045), and MTV (hazard ratio = 2.698, p = 0.033) were significant prognostic factors in cN0 OTSCC patients. The patients with MTV ≥ 7.78 cm3 showed a worse prognosis than those with MTV < 7.78 cm3 (p = 0.037).
The MTV of primary tumor as a volumetric parameter of 18F-FDG PET, in addition to pN stage and AJCC stage, is an independent prognostic factor for survival in cN0 OTSCC.
18F-FDG PET/CT; Oral tongue squamous cell carcinoma; SUV; Metabolic tumor volume; Total lesion glycolysis; Prognosis prediction
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
Advances in reconstruction and conservative surgery and the importance of quality of life (QOL) encouraged this reevaluation of surgery-based treatments for oropharyngeal cancer. We tried to compare treatment outcome and QOL after surgery-based versus radiation-based treatment in oropharyngeal cancer.
The 133 eligible patients were divided into surgery-based and radiotherapy (RT)-based treatment groups. Medical records were reviewed, and EORTC QLQ-C30 and HN65 questionnaires were completed for survivors. Three-year overall survivals, disease-free survivals, locoregional control rates, and QOL scores were compared between the two groups.
Demographic data and overall stages were not significantly different between the two groups, and all survival rates were non-significantly different, either. The scores for most QOL items were equivalent, however, for a few items, scores were significantly better in surgery-based group.
The surgery-based group achieved equivalent treatment outcomes and slightly better QOL scores than the RT-based group. The results of this study suggest that surgery could still be considered as a first-line therapy for oropharyngeal cancer.
Treatment outcome; Quality of life; Oropharyngeal cancer; Surgery; Radiation
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 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
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