miR-935 Inhibits Oral Squamous Cell Carcinoma and Targets Inositol Polyphosphate-4-phosphatase Type IA (INPP4A).

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a common malignancy with poor prognosis. Therefore, novel therapeutic options are needed to improve prognosis of OSCC. Recently, microRNAs (miRs) have received increasing attention as a potential therapeutic tool for carcinomas. However, no definitive miR-based drugs for patients with OSCC have been reported to date. The aim of this study was to identify new miRs potentially involved in cellular processes associated with OSCC malignancy, which could lead to novel therapeutic strategies. MATERIALS AND METHODS: We identified miRs that are modulated in OSCC and possibly regulate OSCC malignancy, using miR microarray on OSCC cell lines. RESULTS: miR-935 and miR-509-3p were down-regulated in OSCC cell lines and patient tissues. When miR-935 was overexpressed in HSC-3-M3 cells, proliferation, migration, and invasion of the cell line was suppressed, whereas apoptosis was increased. Moreover, we showed that the gene inositol polyphosphate-4-phosphatase type I A (INPP4A) is a potential target whose expression is positively regulated by miR-935. CONCLUSION: miR-935 may function as a tumor suppressor by inhibiting OSCC malignancy via INPP4A induction. Therefore, miR-935 can be a new therapeutic candidate for OSCC treatment.

Quadruple Multiple Primary Malignancies: Early Detection of Second Primary Malignancy by Esophagogastroduodenoscopy/Colonoscopy Is Crucial for Patients with Classic Kaposi's Sarcoma.

Currently, Kaposi's sarcoma (KS) is treated following the recommendations of international guidelines. These guidelines recommend esophagogastroduodenoscopy/colonoscopy for detecting multicentric KS of visceral lesions. Second primary malignancies (SPMs) are also a common KS complication; however, information on their detection and treatment is unfortunately not yet indicated in these guidelines. This paper reports on an 86-year-old man who suffered from quadruple primary malignancies: skin classic KS with colon adenocarcinoma, oral squamous cell carcinoma (maxilla), and well-differentiated stomach adenocarcinoma. Gastric cancer was incidentally detected during esophagogastroduodenoscopy, which was performed to detect visceral KS. We suggest that esophagogastroduodenoscopy/colonoscopy be routinely performed during the follow-up of patients with KS. As SPMs are crucial complications in patients with KS, these malignancies should be detected as early as possible.

Thymoma appearing 9 years after the resection of squamous cell carcinoma of the lip: A case report of triple primary tumors and literature review.

The occurrence of second primary tumor (SPT)following malignancy treatment is common. In patients with head and neck (H&N) cancer, SPTs principally occur in the H&N region, lungs or esophagus. Therefore, patient follow-up after cancer treatment is important in order to detect recurrence, metastasis and new primary tumors. However, no standard guidelines on lifelong follow-up imaging are available. Herein, we report a patient who presented with three metachronous primary tumors-squamous cell carcinoma (SCC) of the tongue, SCC of the lip and type A thymoma. The third tumor was incidentally detected during follow-up using contrast-enhanced computed tomography (CT) 9 years following resection of the second tumor. To the best of our knowledge, this specific combination of metachronous tumors has not yet been reported. Based on the literature review, we observed that thymoma occurs following H&N cancer treatment. Therefore, to ensure that the presence of subsequent thymomas is not overlooked, we suggest regular lifelong follow-up using contrast-enhanced CT in patients who had previously been diagnosed with H&N cancer. The literature review revealed that thymomas occur in patients with H&N cancer and should be detected at the earliest convenience.

Triple primary cancer of the head and neck, skin and prostate: A case report and literature review.

Second primary cancer (SPC) is an important prognostic factor for patients with head and neck cancer (HNC); therefore, the association between the prognosis and development of SPC has been well-reported. The use of 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is valuable to examine cancer stage, evaluate treatment responses and investigate suspected relapses or metastases. In the present study, the case of a male patient who was diagnosed with three primary cancer types, including well to moderately differentiated squamous cell carcinoma (SCC) of the mandible, axillary cutaneous poorly differentiated SCC and prostate adenocarcinoma, was described. Among these, mandible cancer was the first diagnosed when the patient was 70 years of age. Synchronous skin and prostate cancer (PRC) types then developed 3 years later. To the best of our knowledge, this is the first report of the aforementioned combination of cancer types. Postoperative FDG-PET was not performed as no lesions of recurrence or metastases of mandible cancer were found. Three years later, the PRC was asymptomatic and was incidentally detected by FDG-PET performed for a preoperative evaluation of skin cancer. It was indicated that FDG-PET could be utilized in patients with HNC due to there being no accurate FDG-PET protocol to detect SPC over a long-term follow-up.

Triple primary malignancies of surface osteosarcoma of jaw, myelodysplastic syndrome and colorectal cancer as a second primary cancer detected by PET2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography: A case report.

Second primary malignancy (SPM) is a severe issue for cancer survivors, particularly for osteosarcoma (OS) survivors. To date, the associations between subsequent SPM and OS have been well reported. Hematogenic and solid malignancies tend to occur following OS treatment. Reportedly, 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is mainly used in OS patients for initial cancer staging, to evaluate the response of neoadjuvant chemotherapy, and when recurrence or metastasis is clinically suspected. The present case report describes a 70-year-old man diagnosed with three primary malignancies: jaw OS, myelodysplastic syndrome and colorectal adenocarcinoma. To the best of our knowledge, this combination of malignancies has not been reported previously. Until now, there is no specific protocol of postoperative FDG-PET for OS patients. Few studies have described OS follow-up methods; therefore, there is no consensus on proper follow-up methods. In the present case report, the colorectal early-stage SPM was observed, without any symptoms, by FDG-PET/computed tomography. To avoid overlooking solid SPMs, it is suggested that FDG-PET should be performed in the long-term follow-up of OS patients.

Dedifferentiated liposarcoma of the oral floor: A case study and literature review of 50 cases of head and neck neoplasm.

Dedifferentiated liposarcoma (DDLS) has a relatively poor prognosis, however this neoplasm rarely occurs in the head and neck. To date, no definite protocol has been established for the diagnosis and treatment of head and neck DDLS. The present study reports the case of a 69-year-old male patient with DDLS of the oral floor. To the best of our knowledge, this is the first documented case of oral floor DDLS. In addition, this is the first reported case with the development of a second primary malignancy following the treatment of head and neck DDLS. A literature review of 50 cases of head and neck DDLS revealed that preoperative biopsy is not reliable for the diagnosis of these tumors and an accurate pathological diagnosis with total resection is preferred.

MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma.

MicroRNAs (miRs) are expected to serve as prognostic tools for cancer. However, many miRs have been reported as prognostic markers of recurrence or metastasis in oral squamous cell carcinoma patients. We aimed to determine the prognostic markers in early-stage tongue squamous cell carcinoma (TSCC). Based on previous studies, we hypothesized that miR-10a, 10b, 196a-5p, 196a-3p, and 196b were prognostic markers and we retrospectively performed miR expression analyses using formalin-fixed paraffin-embedded sections of surgical specimens. Total RNA was isolated from cancer tissues and adjacent normal tissue as control, and samples were collected by laser-capture microdissection. After cDNA synthesis, reverse transcription-quantitative polymerase chain reaction was performed. Statistical analyses for patient clinicopathological characteristics, recurrence/metastasis, and survival rates were performed to discern their relationships with miR expression levels, and the 2-ΔΔCq method was used. miR-196a-5p levels were significantly upregulated in early-stage TSCC, particularly in the lymph node metastasis (LNM) group. The LNM-free survival rate in the low miR-196a-5p ΔΔCq value regulation group was found to be lower than that in the high ΔΔCq value regulation group (P=0.0079). Receiver operating characteristic analysis of ΔΔCq values revealed that miR-196a-5p had a P-value=0.0025, area under the curve=0.740, and a cut-off value=-0.875 for distinguishing LNM. To our knowledge, this is the first study to examine LNM-related miRs in early-stage TSCC as well as miRs and 'delayed LNM' in head and neck cancer. miR-196a-5p upregulation may predict delayed LNM. Our data serve as a foundation for future studies to evaluate miR levels and facilitate the prediction of delayed LNM during early-stage TSCC, which prevent metastasis when combined with close follow-up and aggressive adjuvant therapy or elective neck dissection. Moreover, our data will serve as a foundation for future studies to evaluate whether miR-196a-5p can serve as a therapeutic marker for preventing metastasis.

Outcomes of an international volunteer surgical project for patients with cleft lip and/or cleft palate: A mission in developing Laos.

Cleft lip and/or palate (CL/P) is a common birth defect of complex etiology. CL/P surgery is generally performed in infancy to allow for improvements in esthetics, suckling, and speech disorders as quickly as possible. We have engaged in activities such as free-of-charge surgery for CL/P a total of 12 times from 2001 to 2016 in Lao People's Democratic Republic (Laos). The United Nations has designated Laos as a Least Developed Country; it is one of the poorest countries in Asia. We have carried out our activities for a long time, primarily in CL/P patients who cannot undergo surgery for financial reasons, and we have performed CL/P-related surgeries for 283 patients up to 2016. When we began our activities in 2001, the mean age at first cheiloplasty was 11.6 years, which dropped over time until 2016 when the mean age was 1.8 years. A linear regression analysis showed a significant difference between the age at first lip plasty and the year of first operation (ß = -0.35; P < 0.001). This was likely an effect of continuing to train local medical staff in surgical techniques and donating surgical tools and facilities over a period of 16 years while building a good relationship with local staff. However, the healthcare system in Laos is an obstacle to some patients who still cannot undergo CL/P surgery in infancy for financial reasons. We therefore need to support Laos to provide treatment on their own as we continue to carry out our activities for CL/P patients.

Kikuchi-Fujimoto disease in the regional lymph nodes with node metastasis in a patient with tongue cancer: A case report and literature review.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare self-limiting disorder typically affecting the cervical lymph nodes (LNs), which is often misdiagnosed as other LN-associated diseases. KFD frequently presents with necrotic lesions and recurrences, which are also features of metastatic LNs. Clinicians may thus suspect LN metastasis when they encounter ipsilateral cervical lymphadenopathy in a patient with head and neck cancer. The present study reports the case of a 48-year-old man with tongue cancer and KFD affecting the right edge of his tongue and ipsilateral cervical LNs. LN metastasis was initially suspected, but pathological examination of the dissected LNs revealed one necrotic metastatic lesion and two necrotic KFD lesions. Ipsilateral cervical lymphadenopathy recurred 6 years after the initial surgery, and it was not possible to differentiate clinically between a second primary tumor and recurrent KFD prior to treatment. To the best of our knowledge, this is the first reported case of simultaneous tongue cancer, regional LN metastasis and KFD. This highlights the requirement to consider KFD in the event of LNs with necrotic lesions but no cancerous cells. A combination of clinical and pathological approaches may aid in the diagnosis of KFD, in addition to ruling out LN metastasis in initial and recurrent lymphadenopathies. The present study indicate that a diagnosis of KFD should be considered in patients with head and neck cancer that exhibit necrotic LNs lacking cancerous cells. This is important, as misdiagnosis of KFD as LN metastasis may lead to unnecessary adjuvant therapy.

Indolent growth of low-grade myofibroblastic sarcoma of the cheek mimics benign lesions: A case report and literature review.

Low-grade myofibroblastic sarcoma (LGMS) is a neoplasm of the soft tissue characterized by myofibroblastic differentiation. This type of tumor has been observed in various sites in the whole body, but frequently occurs in the head and neck region. It typically presents as a slow-growing painless mass, which is often mistaken for a benign lesion due to its indolent growth; however, LGMS is a malignant neoplasm. In the present study, a 43-year-old female presented with a 14-mm LGMS lesion in the buccal subcutaneous tissues of the buccinator muscle. The patient had initially noticed the lesion 2-months prior to presenting at the hospital. Following biopsy, the tumor was surgically resected and no recurrence or metastasis was observed during a follow-up time of 2 years. To the best of our knowledge, this case is the first report of LGMS located in the buccal subcutaneous tissue of the buccinator muscle. The present study a literature review of 55 cases of this tumor type in the head and neck region was conducted, revealing that the indolent growth of these lesions may contribute to a delay in diagnosis. The average time between the onset of clinical symptoms and hospital admission is 3.9 months, and this form of tumor is frequently misdiagnosed as a benign lesion. Therefore, the present study suggests that an incisional biopsy may be performed to rule out LGMS when clinicians encounter patients with the aforementioned indolent lesions anywhere in the body. In addition, the avoidance of radiotherapy is recommended following resection of the LGMS tumor, as it may induce LGMS recurrence.

Successful tongue cancer surgery under general anesthesia in a 99-year-old patient in Okinawa, Japan: A case report and review of the literature.

As advances in the medical field have resulted in increased life expectancy, performing surgery under general anesthesia in elderly patients has become an important issue. A 99-year-old Okinawan female was admitted to the hospital presenting with pain in the tongue. Following physical examination, a clinical diagnosis of early stage tongue cancer (T2N0Mx) was confirmed. Early stage tongue cancer is particularly easy to access for surgical resection. By contrast, later stages of tongue cancer are associated with pain, dysphagia and throat obstruction. The patient and their family agreed to surgery due to the worsening pain associated with the tumor and gave informed consent for surgery. Following consultation with a cardiologist and an anesthesiologist, the tongue tumor was surgically resected under general anesthesia. Subsequent to surgery, the patient experienced pain relief and was discharged from the hospital on day 14 post-surgery. The patient was able to maintain the same quality of life, and lived for 5 years and 2 months longer without evidence of disease, surviving to the age of 104 years old. The present case demonstrates that surgery under general anesthesia may be appropriate in patients of an advanced age, with a treatment plan that should ideally be based on careful assessment of the wishes of the patient and their family, medical risks, and benefits and economic costs of alternative treatments, in addition to consideration of the patient's culture.

Impact of metronomic neoadjuvant chemotherapy on early tongue cancer.

PURPOSE: A metronomic schedule of chemotherapy (resulting in a greater frequency of drug delivery) has shown efficacy in head and neck cancer. Our aim was to investigate the overall survival in tongue cancer patients with metronomic neoadjuvant chemotherapy with bleomycin compared to those with surgery alone. METHODS: In this retrospective study, 117 patients with stages I-II tongue cancer, who had undergone surgery, were divided into the "surgery group" or "metronomic neoadjuvant chemotherapy with bleomycin (15 mg × 6) group." The rate of overall survival was the primary outcome measure; the secondary outcome measures included the rates of distant metastasis, regional recurrence, and local recurrence. RESULTS: Of these patients, 54 underwent surgery alone and 63 received neoadjuvant chemotherapy. Neoadjuvant chemotherapy increased overall survival (76 vs. 90 %, P = 0.039). The neoadjuvant chemotherapy group had a significantly lower rates of distant metastasis (0 vs. 13 %, P = 0.003). There was no chemotherapy-related death. CONCLUSIONS: Metronomic neoadjuvant chemotherapy decreased the rates of distant metastasis and increased the overall survival of tongue tumor patients.

Synchronous quadruple multiple primary cancers of the tongue, bilateral breasts, and kidney in a female patient with a disease-free survival time of more than 5 years: a case report.

BACKGROUND: Reports of synchronous multiple primary cancers in patients with oral cancer have recently been increasing because of progress in radiographic diagnostic techniques. Multiple primary cancers in patients with oral cavity cancer mainly occur in the head and neck region, lung, and esophagus. 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography is usually used to identify synchronous multiple primary cancers. CASE PRESENTATION: We herein describe a 69-year-old woman diagnosed with synchronous quadruple multiple primary cancers, namely a squamous cell carcinoma of the mobile tongue, invasive ductal carcinoma of the right breast, intraductal carcinoma of the left breast, and chromophobe renal cell carcinoma of the right kidney. We removed the four tumors over three surgical procedures to reduce the surgical risk because the patient had diabetes mellitus. To the best of our knowledge, this combination of multiple primary cancers has not been reported to date. Importantly, we followed this case for 5 years after surgery. The patient was alive and well with no clinical or radiologic signs of recurrent or metastatic disease at the time of this writing. CONCLUSIONS: In the present case, the kidney cancer could not be detected by 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography but could be detected by contrast-enhanced computed tomography. To avoid overlooking multiple primary cancers of the kidney, we suggest that contrast-enhanced computed tomography should cover a region extending to the inferior margin of the kidney, rather than only to the liver, in patients with oral cavity cancer.