Rac1 activation in oral squamous cell carcinoma as a predictive factor associated with lymph node metastasis.

OBJECTIVES: Secondary lymph node metastasis (SLNM) indicates a poor prognosis, and limiting it can improve the survival rate in early-stage tongue squamous cell carcinoma (TSCC). Many factors have been identified as predictors of SLNM; however, there is no unified view. Ras-related C3 botulinum toxin substrate 1 (Rac1) was found to be a promoter of the epithelial-mesenchymal transition (EMT) and is also attracting attention as a new therapeutic target. This study aims to investigate the role of Rac1 in metastasis and its relationship with pathological findings in early-stage TSCC. MATERIALS AND METHODS: Rac1 expression levels of 69 cases of stage I/II TSCC specimens and their association with clinicopathological characteristics were evaluated by immunohistochemical staining. The role of Rac1 in oral squamous cell carcinoma (OSCC) was examined after Rac1 in OSCC cell lines was silenced in vitro. RESULTS: High Rac1 expression was significantly associated with the depth of invasion (DOI), tumor budding (TB), vascular invasion, and SLNM (p < 0.05). Univariate analyses revealed that Rac1 expression, DOI, and TB were factors significantly associated with SLNM (p < 0.05). Moreover, our multivariate analysis suggested that Rac1 expression was the only independent determinant of SLNM. An in vitro study revealed that Rac1 downregulation tended to decrease cell migration and proliferation. CONCLUSION: Rac1 was suggested to be an important factor in the metastasis of OSCC, and it could be useful as a predictor of SLNM.

Ameloblastic carcinoma of the mandible: a case report.

BACKGROUND: Ameloblastic carcinoma is a malignant form of ameloblastoma and a very rare odontogenic tumor. We report a case of ameloblastic carcinoma that occurred after removal of a right-sided mandibular dental implant. CASE PRESENTATION: A 72-year-old female patient visited her family dentist with a complaint of pain around a lower right implant placed 37 years previously. Although the dental implant was removed with the diagnosis of peri-implantitis, the patient experienced dullness of sensation in the lower lip and was followed up by her dentist, but after no improvement. She was referred to a highly specialized institution where she was diagnosed with osteomyelitis and treated the patient with medication; however, there was no improvement. In addition, granulation was observed in the same area leading to a suspicion of malignancy, and the patient was referred to our oral cancer center. The diagnosis of squamous cell carcinoma was made after a biopsy at our hospital. Under general anesthesia, the patient underwent mandibulectomy, right-sided neck dissection, free flap reconstruction with an anterolateral thigh flap, immediate reconstruction with a metal plate, and tracheostomy. Histological analysis of the resected specimen on hematoxylin and eosin staining showed structures reminiscent of enamel pulp and squamous epithelium in the center of the tumor. The tumor cells were highly atypical, with nuclear staining, hypertrophy, irregular nuclear size, and irregular nuclear shape, all of which were suggestive of cancer. Immunohistochemical analysis showed that Ki-67 was expressed in more than 80% of the targeted area, and the final diagnosis was primary ameloblastic carcinoma. CONCLUSION: After reconstructive flap transplantation, occlusion was re-established using a maxillofacial prosthesis. The patient remained disease-free at the 1-year 3-month follow-up.

Assessment of squamous cell carcinoma of the floor of the mouth with magnetic resonance imaging.

PURPOSE: We aimed to use magnetic resonance imaging (MRI) to determine the relationship between the pathological depth of invasion (DOI), undetectability, and tumor thickness of squamous cell carcinoma of the floor of the mouth. MATERIALS AND METHODS: We retrospectively evaluated the relationship between pathological DOI and MRI detectability, as well as the relationship between pathological DOI and tumor thickness on coronal fat-suppressed contrast-enhanced T1-weighted imaging or coronal T2-weighted imaging. RESULTS: We analyzed 30 patients with squamous cell carcinoma of the floor of the mouth; MRI revealed that the pathological DOI of the 11 undetectable lesions (median 2 mm) was smaller than that of the 19 detectable lesions (median 14 mm) (p < 0.001), and the cut-off value was 3 mm (sensitivity, 0.84; specificity, 0.91; area under the curve, 0.89). Tumor thickness on coronal fat-suppressed contrast-enhanced T1-weighted imaging was assessed in all 19 detectable lesions; however, tumor thickness on coronal T2-weighted imaging could not be assessed in eight cases. Tumor thickness on coronal fat-suppressed contrast-enhanced T1-weighted imaging was found to be significantly associated with the pathological DOI. CONCLUSIONS: Undetectability on MRI indicates superficial lesions with a pathological DOI value that is less than 3 mm. In detectable lesions, tumor thickness on coronal fat-suppressed contrast-enhanced T1-weighted imaging is associated with pathological DOI.

Superselective intra-arterial chemoradiotherapy using altered blood flow compared to conventional systemic chemoradiotherapy for locally advanced oral squamous cell carcinoma: a single-center retrospective study.

PURPOSE: To evaluate the efficacy and safety of superselective intra-arterial (IA) chemoradiotherapy with cisplatin and transcatheter arterial embolization (TAE) on advanced oral cancer, and to compare it with that of systemic chemoradiotherapy. MATERIALS AND METHODS: This single-center retrospective study included 23 consecutive patients with locally advanced oral squamous cell carcinoma from November 2011 to November 2019. Of these, 15 received superselective IA cisplatin chemoradiotherapy with altered blood flow in the branches of the external carotid artery, and eight received systemic chemoradiotherapy. Medical charts were reviewed for the evaluation of patient data, drug toxicity, and antitumor efficacy. RESULTS: Local control rate for the superselective IA infusion group, who underwent 6-7 cycles was significantly higher than that of the systemic chemotherapy group (11/13, 85% vs 3/8, 38%; p = 0.04). Regional control, locoregional control, disease-free survival, and overall survival rates were not significantly different between the groups (p = 0.15-0.907). Acute toxicity rates of grade 3 or higher were not significantly different between the IA and IV chemotherapy groups (p = 0.221). CONCLUSION: Superselective IA chemoradiotherapy with cisplatin using altered blood flow in the branches of the external carotid artery with TAE may be useful for inoperable oral cancer.

Correlation between the magnetic resonance imaging features of squamous cell carcinoma of the buccal mucosa and pathologic depth of invasion.

OBJECTIVE: The objective of this study was to determine correlations between magnetic resonance imaging (MRI) features including radiologic depth of invasion (r-DOI) and pathologic DOI (p-DOI) of squamous cell carcinoma of the buccal mucosa. STUDY DESIGN: In total, 31 lesions were retrospectively evaluated. MRI findings included detectability, buccinator muscle invasion (positive: BMI+, negative: BMI-), buccal fat pad invasion (positive: BFPI+, negative: BFPI-), and r-DOI measured on T2-weighted images (T2-DOI) and contrast-enhanced T1-weighted images (CET1-DOI). These findings were compared to the p-DOI of the tumors. RESULTS: The p-DOI values of undetectable lesions were smaller than those of detectable lesions (P < .001), and the cutoff value was 1 mm. BMI+ and BFPI+ lesions had significantly larger p-DOI values than the corresponding BMI- and BFPI- lesions (P < .001), with cutoff values of 5 and 6 mm, respectively. The correlation coefficient between CET1-DOI and p-DOI was 0.68 (P < .001). CET1-DOI values were larger than p-DOI (P < .001) and the average difference between them was 3.4 mm. T2-DOI was inconclusive in 50% of cases. Interobserver agreements of MRI evaluation were good to very good. CONCLUSION: MRI-derived parameters were useful in estimating p-DOI and may be helpful in predicting the depth of invasion of tumors and the risk of lymph node metastasis.

Usefulness of contrast-enhanced CT in the evaluation of depth of invasion in oral tongue squamous cell carcinoma: comparison with MRI.

OBJECTIVES: There is currently no standardized approach for assessing the depth of invasion (DOI) of oral tongue squamous cell carcinoma via diagnostic imaging. We investigated the usefulness of contrast-enhanced computed tomography (CECT) for estimating the pathological DOI of oral tongue squamous cell carcinoma by evaluating the correlation of pathological DOI with the DOIs on CECT and magnetic resonance imaging (MRI). METHODS: We retrospectively reviewed 21 of 139 patients who underwent radical surgery for primary oral tongue squamous cell carcinoma between 2009 and 2018. The 21 cases were evaluable, without dental artifacts on CECT. DOIs on CECT and MRI, and pathological DOI were measured. RESULTS: The median pathological DOI was 9 mm, that on CECT was 10.9 mm, that on T2-weighted MRI was 14.2 mm, and that on contrast-enhanced T1-weighted MRI was 13.1 mm. The DOIs on CECT and on MRI were larger than the pathological DOI (p = 0.003 to < 0.001). The absolute value of the difference between pathological DOI and DOI on CECT was smaller than that between pathological DOI and DOI on MRI (p = 0.01 and 0.003). DOIs on CECT and on MRI correlated with pathological DOI (r = 0.74-0.66, all p < 0.001). Spearman's correlation coefficient between DOI on CECT and pathological DOI was greater than that between DOI on MRI and pathological DOI. CONCLUSIONS: Compared to the DOI determined on an MRI scan, the DOI determined on a CECT scan correlated with and better approximated pathological DOI. Therefore, CECT can be useful for preoperative staging of patients with oral tongue squamous cell carcinoma.

Effect of postoperative radiotherapy for free flap volume changing after tongue reconstruction.

OBJECTIVE: The purpose of this study was to evaluate the effect of postoperative radiotherapy (RT) on temporal volume changes with a cutaneous free flap (CF) and a myocutaneous free flap (MCF). METHODS: The subjects were 24 men and 11 women (mean age, 50.5 ± 15.5 years) with tongue or floor of mouth cancer. Twenty-seven cases of CF and eight cases of MCF were selected. The flap volume change of the reconstructed tongue was calculated using computed tomography (CT) images taken immediately and at one year postoperatively using the DICOM image processing software OsiriX®. RESULTS: The reduction rate in flap volume at one year postoperatively was 82.0 ± 15% in CF without RT, 70.3 ± 26.1% in CF with RT, 88.5 ± 14.7% in MCF without RT, and 99.5 ± 16% in MCF with RT. The MCF volume was significantly higher compared to the CF volume. Although postoperative RT reduced the CF volume by 30%, there was only a slight reduction in the MCF volume. CONCLUSIONS: We evaluated the effect of postoperative RT on volume reduction in 35 cases of the reconstructed tongue with CF and MCF using a computer-assisted volume rendering technique. In this study, the effect of RT on volume reduction was different between the CF and MCF.

Usefulness of fluorescence visualization-guided surgery for early-stage tongue squamous cell carcinoma compared to iodine vital staining.

BACKGROUND: In the most cases of oral squamous cell carcinoma (OSCC), oral epithelial dysplasia (OED) is found adjacent to the primary tumor. The delineation of surgical margins for OSCC is critical to minimize the risk for local recurrence. The aim of this study is to demonstrate that the fluorescence visualization (FV)- device can delineated the lesion visualizes OED of adjacent primary tumors by histopathologically comparison to conventional iodine vital staining. MATERIAL AND METHODS: The study involved 40 patients with superficial tongue squamous cell carcinoma treated from July 2016 to July 2018 at the Oral Cancer Center, Tokyo Dental College. RESULTS: Cytokeratin 13 (CK13) expression rate in the area of fluorescence visualization loss (FVL) was significantly lower than that in the area of fluorescence visualization retention (FVR). In addition, CK17, Ki-67, and p53 expression rates were significantly higher in FVL than FVR. There was no significant difference in the delineation rate or area between FVL and iodine-unstained area. High-grade dysplasia was observed most frequently at the FV and iodine-unstained boundary, but no significant pathological differences were found. CONCLUSION: We strongly suggest the FV-guided surgery is a useful method for accurate resection in early-stage tongue squamous cell carcinoma.

Which Factors Affect the Long-Term Survival of Patients With Oral Squamous Cell Carcinoma With Distant Metastasis?

PURPOSE: The development of distant metastases (DMs) in patients with oral squamous cell carcinoma (OSCC) leads to dismal prospects for survival. The present study aimed to identify the risk factors for DM development and long-term survival. PATIENTS AND METHODS: The present study was a retrospective cohort study of patients with OSCC at a single institution. The predictor variables were age, gender, lymph node classification, histologic grade, neck dissection, infiltrative growth pattern (INF), vascular/lymphatic invasion, perineural invasion (PI), extranodal extension, local recurrence, nodal metastasis, DMs, interval to the diagnosis of DMs, and surgery for DMs. The primary outcome variables were the 5-year overall survival (OS) and median survival time (MST), which were estimated using the Kaplan-Meier method. Cox hazard models were used to identify the risk factors for DM development. RESULTS: The cohort included 526 patients; the data from 402 were available for analysis. Of these 402 patients, 37 developed DMs. On multivariate analysis, clinical N1 (cN1)-cN2 (hazard ratio [HR], 3.36), moderate/poor differentiation (HR, 2.51), INFc (HR, 3.27), vascular/lymphatic invasion (HR, 2.95), and PI (HR, 2.17) were independent predictors of DM development. The 5-year OS was 84.6% for the non-DM patients and 9.7% for the DM patients, with a MST of 16.9 months. In those with DMs with cN0, the 5-year OS was 18.2% and the MST was 37.2 months. For those with DMs with cN1-cN2, the 5-year OS was 4.7% and the MST was 12.9 months. In patients with an interval to the DM diagnosis of 10.0 months or longer, the 5-year OS was 20.0% and the MST was 38.6 months. In the patients with an interval to the DM diagnosis of less than 10.0 months, the MST was 11.7 months. The 5-year OS of the patients who had undergone pulmonary metastasectomy was 60.0% and the MST of the nonsurgery group was 16.0 months. CONCLUSIONS: In the patients with DMs, stage cN0 and a late interval to DM diagnosis were associated with long-term survival. Pulmonary metastasectomy could be worth considering to improve survival.

Ten-year Clinical Trends among 575 Consecutive Oral Cancer Patients at Tokyo Dental College Oral Cancer Center.

The facilities comprising Tokyo Dental College (TDC) -the college itself and its medical institutions at Suidobashi, Ichikawa, and Chiba - have been officially recognized as a center for treating oral cancer. The TDC Oral Cancer Center (OCC) was established on April 1, 2006. It provides comprehensive medical care, including that aimed at recovery of postoperative function, such as restoration of stomatognathic function, dysphagia therapy, and placement of maxillary prostheses. The purpose of this study was to investigate patient trends at TDC-OCC over the 10 years following its establishment in order to determine how the safe and high-quality cancer care already provided might be even further improved. Oral cancer patients attending TDC-OCC between April 2007 and March 2017 were investigated. Clinical information was obtained from medical records and analyzed, including that on patient numbers, age, sex, primary site of tumor, clinical stage, and surgery provided. There were 758 new cases, and the number of new cases showed an annual increase. Among the total number of new patients, 575 (75.9%) represented primary cases. The number of operations also showed an increase, which correlated with the increase in the number of patients. The incidence in oral cancer has increased in several countries, including Japan. Oral cancer can be observed macroscopically and touched. In contrast to with cancers at many other sites, and despite various diagnostic devices for early detection having been developed, however, cases are often advanced when first encountered. Many advanced cases were treated at TDC-OCC, and the number of reconstructive operations following progressive cancer also increased over time.

Magnetic resonance imaging findings of styloglossus and hyoglossus muscle invasion: Relationship to depth of invasion and clinical significance as a predictor of advisability of elective neck dissection in node negative oral tongue cancer.

PURPOSE: By comparing styloglossus and hyoglossus muscle invasion (SHMI) of oral tongue squamous cell cancer (OTSCC) on MR imaging to pathological depth of invasion (DOI) and prognosis, we aimed to evaluate the clinical significance of MR imaging findings of SHMI. METHOD: Forty-five, early stages and clinically N0 OTSCCs were retrospectively reviewed. Data included pathological DOI, DOI on MR imagings, two-year potential cervical lymph node positive, locoregional control, disease-free survival, and overall survival. Data were statistically compared between the groups with MR evidence of SHMI (SHMI+) and without MR evidence of SHMI (SHMI-). RESULTS: There were 17 SHMI + and 28 SHMI-. Elective neck dissections performed on 13 cases revealed five node positive cases, all of which were SHMI + . Pathological DOI in SHMI + was significantly larger than SHMI- (average 9.0 vs 4.6 mm, p < 0.001). All SHMI + revealed pathological DOI larger than 4 mm. The two-year potential cervical lymph node positive rate of SHMI + was significantly higher than SHMI- (p =  0.01). Locoregional control rate and disease-free survival of SHMI+ were significantly lower than in SHMI- (p =  0.02). There was no significant difference in overall survival. Interobserver agreement in evaluation of SHMI on MR imaging was good (kappa value = 0.72, p <  0.001). CONCLUSIONS: Pathological DOIs of SHMI + were all larger than 4 mm, which is the cut-off point that National Comprehensive Cancer Network recommends for neck dissection, and SHMI + had a worse prognosis than SHMI-. SHMI + can be used as a criterion for elective neck dissection.

Undetectability of oral tongue cancer on magnetic resonance imaging; clinical significance as a predictor to avoid unnecessary elective neck dissection in node negative patients.

METHODS:: We retrospectively reviewed early stage oral tongue cancer patients treated with radical surgery with clinically N0, between May 2009 and February 2016. Collected data include age, sex, pathological DOI, DOI on MRI, locoregional control rate, disease-free survival rate, and overall survival rate. These data were statistically compared between the detectable lesion (DL) group and undetectable lesion (UL) group on MRI. Interobserver agreement in evaluation of detectability of the oral tongue cancer was assessed by k statistics. RESULTS:: Total of 53 patients were studied, and 28 were DLs and 25 ULs. Pathological DOI in UL was significantly smaller than that of DL (average 1.7 vs 4.6 mm, p < 0.001). Cut-off value between UL group and DL group was 3.5 mm (sensitivity 96 %, specificity 75 %). 96 % of ULs had pathological DOI smaller than 4 mm, the recommended cut-off value for neck dissection. There was no significant difference in locoregional control rate (p = 0.24), disease-free survival rate (p = 0.24) or overall survival rate (p = 0.92). Interobserver agreement in evaluation of detectability on MRI was very good ( k-value = 0.89, p < 0.001). CONCLUSIONS:: When oral tongue cancer is not detected on MRI, it indicates pathological DOI being smaller than 4 mm, which may imply that elective neck dissection is unnecessary.

Squamous Cell Carcinoma of Maxillary Gingiva Progressing to Disseminated Carcinomatosis of Bone Marrow.

Disseminated carcinomatosis of the bone marrow (DCBM) is characterized by diffuse metastasis to bone marrow and sudden mortality. To the best of our knowledge, no studies to date have reported progression of oral squamous cell carcinoma to DCBM. Herein, we report a case of squamous cell carcinoma in the maxillary gingiva suspected of progressing to DCBM. A 64-year-old woman presented with white lesions on the left maxillary gingiva. The lesions were diagnosed as squamous cell carcinoma (T2, N0, M0), and partial maxillectomy performed. Two years and 5 months after surgery, metastasis was noted in the left cervical lymph node and left radical neck dissection carried out. The subsequent diagnosis was right cervical lymph node metastasis and multiple bone metastases. The patient also presented with thrombocytopenia, anemia, and elevated levels of alkaline phosphatase, probably due to metastatic bone disease. Although various antitumor therapies were administered, the patient died 6 months after diagnosis of multiple bone metastases.

Case of Inverted Supernumerary Tooth in Nasal Cavity.

The eruption of a tooth into the nasal cavity is a rare clinical entity. We report a case of an inverted supernumerary tooth in the nasal cavity. A 2-year-old boy was referred to our institution after examination at a local otorhinolaryngology department for otitis media. Radiological examination revealed a tooth-like structure in the right nasal cavity. The tooth was protruding from the floor of the nasal cavity along with granulation tissue. The diagnosis was an inverted tooth in the right nasal cavity. Forceps extraction was performed under general anesthesia.

Imaging Findings in AIDS-related Oral Kaposi's Sarcoma.

Kaposi's sarcoma (KS) is one of the most common diseases in patients with acquired immunodeficiency syndrome, but is rarely encountered in dental practice in Japan. We encountered a case of oral KS (OKS) presenting in the hard palate, gingiva, and tongue in a 41-year-old man. We report the results of imaging, including computed tomography (CT), magnetic resonance imaging, and positron emission tomography/CT in this case. The process leading to an imaging diagnosis of OKS is discussed, emphasizing the importance of collating clinical, laboratory, pathological, and radiological findings. The present results suggest that mapping of accurate tumors is very important in cases of OKS, and that multiple or bilateral manifestations, ill-defined margins, osteolysis, and swollen lymph nodes, in particular, need to be taken into account.

Postoperative Conversion Disorder in Elderly Oral Cancer Patient.

Conversion disorder is a condition in which psychological stress in response to difficult situations manifests as physical symptoms. Here, we report a case of postoperative coma due to conversion disorder in an elderly oral cancer patient. An 82-year-old woman was referred to Tokyo Dental College Chiba Hospital with a mass lesion on the tongue. A biopsy revealed a well-differentiated squamous cell carcinoma. Surgical treatment was performed for the tongue carcinoma and tracheotomy for management of the airway. On postoperative day 5, the patient exhibited loss of consciousness (Glasgow Coma Scale: E1, VT, M1; Japan Coma Scale: III-300). The patient's vital signs were all normal, as were the results of a full blood count, brain-CT, MRI, and MRA. Only the arm dropping test was positive. Therefore, the cause of the coma was diagnosed as conversion disorder. Seven hours later, the patient showed a complete recovery.

Case of cervical carcinoma of unknown primary treated through multidisciplinary approach.

Carcinoma of unknown primary (CUP) is where the primary site remains unidentified even though metastases are present, and accounts for 3-5% of all human malignancies. Here, we report a multidisciplinary approach to the treatment of a squamous cell CUP occurring in the left cervical region. Following radical surgery for carcinoma of the colon, swelling occurred in the left cervical region in a 59-year-old man. The results of an incisional biopsy indicated a diagnosis of squamous cell carcinoma (SCC), and he was referred to our department for examination. The primary carcinoma was not identifiable despite an extensive diagnostic workup including a physical examination, fiberoptic endoscopy, computed tomography, magnetic resonance imaging, and fluorodeoxyglucose F18 positron emission tomography, resulting in a diagnosis of an SCC of unknown in the cervical region. The patient was initially treated with three cycles of docetaxel 75 mg/m(2)/day, cisplatin 100 mg/m(2)/day, and 5-fluorouracil 1,000 mg/m(2)/day as induction chemotherapy. This was followed by concurrent chemoradiotherapy (cisplatin 30 mg/m(2)/day, 70 Gy) and neck dissection. Subsequent pathological examination revealed no vestiges of the tumor. The patient has remained free from recurrence and metastasis for 6 years.

Osseous choristoma in child with strong vomiting reflex.

Osseous lesions within soft tissue such as the tongue are extremely rare. Here, we report an osseous choristoma on the posterior portion of the tongue in a patient with a strong vomiting reflex. The patient was an 11-year-old boy who presented with the chief complaint of swelling on the posterior portion of the tongue. A pedunculated tumor 8-mm in diameter with distinct borders was observed slightly to the right of the midline of the dorsum of the tongue and slightly anterior to the circumvallate papillae. The clinical diagnosis was a right lingual circumvallate papilla fibroma. A further examination conducted under general anesthesia in July 2012 confirmed a pedunculated and solid mass in the area of the circumvallate papillae. As these results suggested a benign tumor, the mass was resected. Histopathological findings on harvested bone and fibrous connective tissue covered with a layer of squamous cells led to a diagnosis of osteoma. At 18 months postoperatively, there were no signs of recurrence.

Intraosseous schwannoma originating in inferior alveolar nerve: a case report.

Schwannomas (neurilemmomas) are benign neoplasms derived from Schwann cells of the neurilemma and appear most frequently on the auditory nerve or peripheral nerves of the skin. They arise in the oral and maxillofacial region infrequently, and very rarely in the center of the jaw. We herein present a case of a rare mandibular intraosseous schwannoma derived from the main trunk of the inferior alveolar nerve in a 33-year-old man. Fusiform expansion in the mandibular canal was observed and a mass showing the target sign in the mandibular canal was confirmed on T2-weighted and Gd contrastenhanced T1-weighted MRI. Based on these findings, an inferior alveolar nerve-derived schwannoma or other benign nervous system neoplasm was diagnosed. A buccal side cortical bone flap in the mandibular molar region was removed to expose the mass, which was then peeled away from the nerve fibers and completely removed. Some inferior alveolar nerve fibers that were connected to the mass were removed at the same time, but the remaining nerve fiber bundle was preserved. Histopathology confirmed the diagnosis of a schwannoma with Antoni type A and Antoni type B regions. Although the patient experienced extremely mild paresthesia in the skin over the mental region and mental foramen at immediately after surgery, this had almost entirely disappeared at 7 years and 4 months later, and there has been no tumor recurrence.