Atypia of undetermined significance on thyroid fine needle aspiration: surgical outcome and risk factors for malignancy

PURPOSE: This study was performed to analyze the surgical pathology results of the "atypia of undetermined significance" (AUS) category from thyroid fine needle aspiration (FNA) and to describe the characteristics to distinguish a malignant from a benign nodule. METHODS: A retrospective analysis was done on 116 patients who underwent thyroid surgery from December 2008 to December 2012, following a diagnosis of AUS from preoperative thyroid FNA. We investigated the age, gender, size and site of the nodules, ultrasonographic criteria, cytological features, the number of atypia results after repeated FNAs, surgical method, and final pathologic results. RESULTS: Sixty-five out of 116 patients underwent total thyroidectomy and the rest had partial thyroidectomy. The final pathologic results were 41 malignancies (35.3%) and 75 benign diseases (64.7%). AUS was divided into group 1: 'cannot rule out malignancy' or group 2: 'cannot rule out follicular neoplasm'. After surgery, group 1 revealed papillary thyroid cancer in most cases and group 2 revealed follicular adenoma in most cases. Age over 40 years, ultrasonographic findings suggestive of malignancy, more than 2 results of atypia from repeated FNAs and nodules less than 2 centimeters were risk factors for malignancy on univariate analysis. Multivariate analysis showed that ultrasonographic findings suggestive of malignancy was a significant risk factor for malignancy. CONCLUSION: For proper evaluation of the risk for malignancy in thyroid AUS patients, the ultrasonographic criteria should be considered along with other clinicopathological findings such as age, nodule size, number of atypia, cytologic features.

Risk Factor of Invasive Breast Cancer in Patients with Preoperative Diagnosis of Ductal Carcinoma in Situ

PURPOSE: Ductal carcinoma in situ (DCIS), unlike invasive ductal carcinoma, does not require sentinel lymph node biopsy or axillary lymph node dissection because the possibility of axillary lymph node metastasis is low. However, occasionally, despite preoperative diagnosis of DCIS, invasive ductal carcinoma can be diagnosed by postoperative biopsy. Therefore, a study of the associated risk factors is necessary. METHODS: 198 patients with an initial diagnosis of DCIS, treated between February 2005 and December 2009, were retrospectively analyzed. Associations between clinical and pathologic factors were analyzed for significance using univariate and multivariate analyses. RESULTS: Of the 198 patients, 57 (28.8%) were found to have invasive disease on final pathology. Multivariate analysis revealed 4 independent predictors of invasive cancer upon final pathology: diagnosis by needle biopsy (OR, 3.165; P=0.008), positive p53 on preoperative biopsy (OR, 2.494; P=0.019) DCIS size (>2 cm) on microscopic finding (OR, 2.683; P=0.014), and relatively young age (OR, 0.958, P=0.046). Of the 13 patients with positive axillary lymph nodes, 11 (84.6%) were shown to have invasive cancer on final pathology (P<0.001). CONCLUSION: In cases of preoperative diagnosis based on needle biopsy, positive p53, large tumor, and relatively young age, an SLNB procedure can be considered because in almost 30% of the patients an invasive carcinoma is found after surgery.

Expression of Nonsteroidal Anti-Inflammatory Drug-Activated Gene(NAG-1) as a Prognostic Marker in Oral Tongue Squamous Cell Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Our previous study showed that nonsteroidal anti-inflammatory drug-activated gene (NAG-1) induced apoptosis in tongue cancer cells. However, the NAG-1 expression in tongue cancer and normal tissues was not studied. The aim of this study was to investigate the expression of NAG-1 in oral tongue cancer and normal tissues and to identify the relationship between NAG-1 expression and the prognosis of tongue cancer patients to determine whether NAG-1 can be used as a valuable prognostic marker in tongue cancer. SUBJECTS AND METHOD: The medical records and pathologic reports of 42 tongue cancer patients who received surgery as primary treatment were surveyed. Tongue cancer and normal tissues, which were obtained during the operation, were stained with anti-NAG-1 antibody using the immunohistochemical method and the H-score was calculated. RESULTS: As a result, the higher expression of NAG-1 was observed in the cancer tissues than in the normal tissues. NAG-1 expression was noted to be higher in cases of tongue cancers with more invasion, positive lymph node metastasis, and poor prognosis. A 5-year survival rate was significantly decreased in cases showing higher NAG-1 expression in the cancer tissues than in the normal tissues. CONCLUSION: The higher NAG-1 expression in the cancer tissue suggests malignant changes in cancer tissue and poor prognosis. Therefore, NAG-1 may be a useful prognostic marker in tongue squamous cell carcinoma.

Anti-adhesive Effect of GUARDIX-SL(R) after Endoscopic Sinus Surgery / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Adhesion after sinus surgery represents a potential source of surgical failure. GUARDIX-SL(R) which is composed of sodium hyaluronate and sodium carboxymethyl cellulose, is an effective agent that can be used as a surgical adjuvant to decrease adhesion in the abdominal surgery. Therefore, we evaluated the clinical efficacy and safety of the GUARDIX-SL(R) for the prevention of adhesion after endoscopic sinus surgery. SUBJECTS AND METHOD: This study was randomized and double-blinded. At the completion of endoscopic sinus surgery, 6 mL GUARDIX-SL(R) was applied on Merocel(R) and repeatedly applied on the middle meatus after removal of Merocel(R) (n=22). As a control group, normal saline was applied instead of GUARDIX-SL(R)(n=22). Endoscopic examination was performed at 3 days, 1 week, 2 weeks, and 4 weeks, postoperatively. Adhesion formation was graded as G0-G4, and CT scoring was also performed. RESULTS: The rate of adhesion formation was the highest at 2 weeks after operation and was significantly lower in the GUARDIX-SL(R) treated group than in the control throughout the period of observation. The cases were divided into 3 groups according to the CT scores at 2 weeks after operation: The groups with the GUARDIX-SL(R) treatment also showed lower adhesion formation than the control. The safety profile of the patients was normal at 4 weeks postoperatively. CONCLUSION: The results suggest that GUARDIX-SL(R) may be an efficacious and safe material in decreasing the incidence of adhesion after sinus surgery.

Ectopic Pancreas Presenting as a Duodenal Obstructing Mass

An ectopic pancreas, also known as a heterotopic or aberrant pancreas, is defined as pancreas tissue lying outside its normal location and lacking anatomic or vascular connections with the pancreas. Most occurrences of an ectopic pancreas are located in the stomach, duodenum, or jejunum. However, an ectopic pancreas can sometimes be found in unusual sites such as the Meckel's diverticulum, gallbladder, umbilicus, mediastinum and fallopian tubes. An ectopic pancreas rarely produces clinical symptoms, but occasionally can result in varying symptoms according to its location, size and involvement of the overlying mucosa. Herein, a case of 41-year-old male with an ectopic pancreas in the duodenum, presenting as a duodenal obstructing mass, is reported.

Combination Gene Therapy Using IL-2 and GM-CSF Genes Transferred by a Defective Infectious Single Cycle Herpes Virus (DISC Virus) in Head and Neck Squamous Cell Cancer Model / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is an attenuated virus originally produced as a viral vaccine, but it also serves as an efficient gene transfer vehicle. The main goals of this study were to examine determinants of gene transfer using DISC vectors for squamous cell carcinoma and to evaluate the efficacy of vaccination with the DISC virus carrying a combination of immunomodulatory genes (IL-2, GM-CSF) as cancer therapy in a model of squamous cell cancer in the C3H/HeJ mice. MATERIALS AND METHODS: We determinated the gene and protein expression of DISC-IL-2 and DISC-GM-CSF transfected SCCVII cells by RT-PCR and ELISA method. Also, we evaluated the ex vivo vaccination effects of DISC-IL-2 and DISC-GMCSF on preventing the development of SCCVII tumor. RESULTS: SCCVII cells transduced by the DISC virus vector (MOI=10) carrying the IL-2, or the GM-CSF gene, produced nanogram quantities of IL-2 or GM-CSF per 10(6) cells. Of particular interest was the observation that cells irradiated at different doses (5,000 cGy, 10,000 cGy) secreted levels of GM-CSF or IL-2 that were comparable to non-irradiated cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-IL-2 or DISC-GMCSF resulted in protection against subsequent tumor challenge (p<0.01). Among the multiple immunomodulatory transgenes vaccination groups, the DISC-GMCSF transfected vaccine showed the greatest suppression of tumor development and growth (p<0.001). CONCLUSION: These data demonstrate that: 1) The DISC virus vector is capable of efficient gene transfer to SCCVII cells, 2) The GM-CSF secreting, genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor cell challenge and suppressed tumor growth in our tumor model. The DISC virus-mediated, cytokine gene transfer may prove to be useful in clinical therapy for head and neck cancers.

En-bloc Dissection of Deep and Superficial lobe of Parotid gland with Preserving the Facial Nerve / 대한이비인후과학회지

Total parotidectomy is indicated when the tumor is originated from a deep lobe of the parotid gland. Because of the facial nerve, the usual sequence of total parotidectomy of a deep lobe tumor is to first perform superficial parotidectomy separately and then to remove the deep lobe. However, it is desirable to remove the parotid gland en-bloc while preserving the facial nerve. We designed a simple procedure that could remove a deep lobe tumor without separating the superficial portion of the parotid gland. This surgical technique is discussed with the present cases.

DISC-GMCSF (GM-CSF Gene Transduced Defective Infectious Single Cycle Herpes Virus) Gene Therapy in the Established SCCVII squamous cell carcinoma model / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Over the past five years, preclinical studies evaluating viral-vector-mediated gene transfer in the treatment of head and neck cancer have reported promising results. The main goal of this study was to evaluate the efficacy of intra-tumoral treatment with DISC virus (defective infectious single cycle herpes virus) carrying a GM-CSF immunomodulatory genes as cancer gene therapy. MATERIALS AND METHOD: Using the SCCVII squamous cell carcinoma model, we determined the in vivo GM-CSF production by ELISA method and evaluated the in vivo effects of DISC-GMCSF on the established tumor model. One of the following preparations was injected every two days to a total of three-doses intratumorally: group I (control): PBS alone, group II: heat inactivated DISC-GMCSF, group III: DISC-GMCSF. To prove the specific anti-tumor response, we analyzed the surface phenotype of tumor infiltrating cells. A flow cytometric analysis was performed using FACScan. RESULTS: Clinically relevant gene transfer could be possible by direct injection of tumors in situ. Intratumoral injection of the DISC-GMCSF (GM-CSF gene transduced defective infectious single cycle herpes virus) resulted in effective in vivo production of cytokines (4,500 pg/0.5 g tumor tissue), but as the progeny of the DISC virus could not be infected by other host cells, the effective cytokine production time seems limited. However, the DISC vector was safe and also allowed to be administered repeated treatments as needed. Effects of DISC-GMCSF injection on tthe established syngeneic tumor model showed the greatest inhibition of tumor growth in the DISC-GMCSF treated group (control vs DISC-GMCSF, p<0.01). In contrast to this, heat inactivated DISC-GMCSF showed no significant tumor suppression effect. It was interesting to note from our in vivo analysis of tumor infiltrating cells that treatment of flank tumors with the DISC-GMCSF virus resulted in a significant increase in the percentage of CD8 positive cells within the tumor (control vs DISC-GMCSF, p<0.05). CONCLUSION: Intratumoral injection of DISC-GMCSF significantly suppressed the tumor growth in established tumor model and induced intratumoral increase in immune effector cells. The results not only confirmed clinically relevant gene transfer but also demonstrated the gene transfer to be an effective anti-cancer therapy.