[Neoadjuvant Epirubicin-Cyclophosphamide Therapy followed by Nab-Paclitaxel in Patients with Operable Breast Cancer-A Single-Center Phase â ¡ Trial].

Clinical studies have confirmed that nab-paclitaxel(nab-PTX)therapy is effective and safe in patients with metastatic breast cancer. Neoadjuvant chemotherapy(NAC) with nab-PTX has resulted in a pathological complete response (pCR) rate of 29% in all cases and 58% in HER2-positive cases. However, these data were obtained from an overseas study, and the effectiveness and safety of NAC with nab-PTX remain unclear in Japan. Thus, the present study was conducted to investigate these aspects. In patients with T1-3, N0-2, M0 breast cancer, 4 cycles of 260 mg/m2 nab-PTX were administered every 3 weeks after 4 cycles of EC therapy(100 mg/m2 of epirubicin and 600 mg/m2 of cyclophosphamide)as NAC. In HER2- positive patients, trastuzumab was used in combination with nab-PTX. Overall, 14 patients were registered between October 2014 and October 2018. One patient who had requested for another drug after providing informed consent was excluded, and the remaining 13 patients were analyzed. The primary endpoint was pCR rate. The median age of the subjects was 57 years, and the median tumor diameter was 35 mm. There were 7 cases of Stage Ⅱ disease and 6 cases of Stage Ⅲ disease. As for tumor subtype, there were 7 cases of Luminal-type, 2 cases of Luminal- HER2-type, 4 cases of HER2-type, and no triple negative-type tumors(the cut-off values for estrogen receptor [ER] and progesterone receptor were both 1%). The objective response rate to NAC was 77%(10/13 cases), and no PD was observed. The pCR rate was 54%(7/13 cases): 2 patients had Luminal-type tumors, 1 had a Luminal-HER2-type tumor, and 4 had HER2-type tumors. Predictive factors for pCR were ER negativity and HER2 positivity. Common adverse events of chemotherapy were hair loss, pain, malaise, anemia, dysgeusia, constipation, itchiness, and numbness, but their severity was modest, and they were manageable. This study suggests the efficacy and safety of nab-PTX after EC therapy in Japanese patients with operable breast cancer.

Ghost cell odontogenic carcinoma arising in dentinogenic ghost cell tumor with next-generation sequencing cancer panel analysis: A case report.

OBJECTIVE: Ghost cell odontogenic carcinoma (GCOC) is a rare tumor that can sometimes occur from dentinogenic ghost cell tumor (DGCT). STUDY DESIGN: We report a case of GCOC arising from DGCT that underwent long-term follow-up with multiple biopsies. The biopsy specimens were analyzed using a next-generation sequencing cancer panel. RESULTS: Histopathology of the resected tumor revealed that the boundary between benign and malignant components was clear. In immunohistochemistry, the nuclei of malignant tumor cells were positive for ß-catenin and LEF-1. CTNNBI mutation was detected in all 4 biopsy specimens, and all of these mutations were identical (c.98C>G (p.Ser33Cys)). No other gene mutations that could definitively cause malignant transformation were detected. CONCLUSIONS: This case suggested that GCOC and DGCT are ghost cell neoplasms caused by a common mutation of CTNNB1 and that the malignant cells of GCOC are derived from cells that specifically differentiate into ghost cells.

Determination of diagnostic and predictive parameters for vertical mandibular invasion in patients with lower gingival squamous cell carcinoma: A retrospective study.

Vertical mandibular invasion of lower gingival squamous cell carcinoma (LGSCC) determines the method of resection, which significantly affects the patient's quality of life. Therefore, in mandibular invasion by LGSCC, it is extremely important to monitor progression, specifically whether invasion is limited to the cortical bone or has progressed to the bone marrow. This retrospective study aimed to identify the diagnostic and predictive parameters for mandibular invasion, particularly vertical invasion, to enable appropriate selection of the method of mandibular resection. Of the patients who underwent surgery for LGSCC between 2009 and 2017, 64 were eligible for participation in the study based on tissue microarrays (TMA) from surgical specimens. This study analyzed morphological features using computed tomography (CT), and metabolic characteristics using maximum standardized uptake value (SUVmax), peak value of SUV (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Moreover, immunohistochemical analysis of proteins, including parathyroid hormone-related protein (PTHrP), interleukin-6 (IL-6), E-cadherin, and programmed cell death-1 ligand 1 (PD-L1), was performed. Statistical analysis was performed using univariate logistic regression analysis with the forward selection method. The present study showed that MTV (≥2.9 cm3) was an independent diagnostic and predictive factor for positivity of mandibular invasion. Additionally, TLG (≥53.9 bw/cm3) was an independent diagnostic and predictive factor for progression to bone marrow invasion. This study demonstrated that in addition to morphological imaging by CT, the volume-based parameters of MTV and TLG on fluorine-18 fluorodeoxyglucose positron emission tomography were important for predicting pathological mandibular invasion in patients with LGSCC. A more accurate preoperative diagnosis of vertical mandibular invasion would enable the selection of appropriate surgical procedure for mandibular resection.

Diagnosis and treatment of secretory carcinoma arising from the oral minor salivary gland: Two case reports.

INTRODUCTION: Secretory carcinoma (SC) is a malignancy of the salivary glands, which is similar to SC of the breast regarding its association with neurotrophic tyrosine receptor kinase fusion-positive gene. SC is a recently described salivary gland tumor, and there are a few reports describing oral minor salivary gland-derived SC. We reported two cases of SC in the oral cavity and reviewed the literature. PATIENT CONCERNS: The patients included a 65-year-old Japanese woman who presented with a mass of the upper lip and an 84-year-old Japanese man who presented with a mass on the buccal mucosa. DIAGNOSIS: Diagnosis was based on histomorphological and immunohistochemical findings and identification of a specific translocation of the ETS variant 6-neurotrophic receptor tyrosine kinase 3 gene fusion. Case 1 was finally diagnosed using reverse transcription-polymerase chain reaction with formalin-fixed paraffin-embedded tissue samples, while case 2 was diagnosed using fluorescence in situ hybridization analysis. INTERVENTIONS AND OUTCOMES: In case 1, excisional biopsy was done and there was no recurrence observed in five-year follow-up. In case 2, tumor resection was done and there was no recurrence observed in two-year follow-up. CONCLUSION: It is highly likely for many cases of SC to be initially diagnosed as acinic cell carcinoma (AciCC) owing to their similar histological findings. The treatment strategy for minor salivary gland-originated SC is similar to that of AciCC; however, SC is often highly malignant and involves a high risk of cervical lymph node metastasis. Thus, establishing an accurate diagnosis together with pathologists and confirming the presence of the ETS variant 6-neurotrophic receptor tyrosine kinase 3 fusion gene using genetic analysis is important.

CD15+ tumor infiltrating granulocytic cells can predict recurrence and their depletion is accompanied by good responses to S-1 with oral cancer.

BACKGROUND: It has been reported in oral squamous cell carcinoma (OSCC) that myeloid-derived suppressor cells infiltrate tumor tissues. This study examined whether S-1 chemotherapy changes immune cell populations in the tumor microenvironment. METHODS: We examined 71 patients with of OSCC, including 51 patients who received preoperative S-1 chemotherapy. Immunohistochemistry for PD-L1, CD8, forkhead box protein 3 (FOXP3), and CD15 was performed using biopsy and resected specimens. RESULTS: The numbers of CD8+ , FOXP3+ , and CD15+ cells in resected specimens were significantly decreased by S-1 chemotherapy. The reduction of the proportion of CD15+ cells significantly differed between responders and nonresponders. Most responders were distributed into the group with low PD-L1 expression and a low density of CD8+ cells before chemotherapy. Furthermore, many patients with recurrence exhibited a high density of CD15+ cells in biopsy specimens. CONCLUSION: Preoperative S-1 chemotherapy can potentially improve prognosis by reducing CD15+ cells in the tumor microenvironment.

An immunohistochemical and genetic study of BRAFV600E mutation in Japanese patients with ameloblastoma.

Ameloblastoma is an odontogenic tumor of the jaw. It most frequently occurs in the mandible, and less often in the maxilla. Mandibular ameloblastoma harbors a BRAF mutation that causes a valine (V) to glutamic acid (E) substitution at codon 600 (BRAFV600E ). We examined specimens from 32 Japanese patients to detect the prevalence of the BRAFV600E mutation, and to evaluate the relationship between immunohistochemical (IHC) expression and genetic results, of BRAFV600E+ ameloblastoma. Among the 32 cases, 22 (69%) were IHC positive for BRAFV600E protein, and 10 (31%) were IHC negative; and polymerase chain reaction showed 16 of 21 tested cases (76%) carried the BRAFV600E mutation. Our findings indicate that that samples that stain IHC positive for BRAFV600E protein are more likely to carry the BRAFV600E mutation. These results support assessments for BRAF mutations, and the use of BRAF inhibitors as targeted therapy for ameloblastoma in Japanese patients.

Histopathological changes in tumor budding between biopsy and resected specimens from patients treated with preoperative S-1 chemotherapy for oral cancer.

BACKGROUND: S-1 is an oral anticancer agent containing tegafur, a prodrug of 5-fluorouracil (5-FU). Preoperative S-1 chemotherapy is performed to prevent tumor proliferation before surgery in oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate the effects of preoperative S-1 chemotherapy on tumor budding. METHODS: We examined 248 cases of OSCC and evaluated the budding scores in biopsy and resected specimens by keratin immunohistochemistry. RESULTS: In S-1-untreated patients, the budding scores in resected specimens tended to show a mild increase. S-1 treatment had the effect of lowering the budding score, although some cases with dramatically increased budding scores in resected specimens were found in the early phase of administration. Relapse-free survival showed a significant difference (P < .01) according to the presence or absence of S-1 treatment among patients with high budding scores. CONCLUSIONS: The present findings indicate that S-1 administration may be more effective in patients with high budding scores than in those with lower budding scores.