Correlation during the extent of surgical resection, oral function and quality of life after tongue cancer surgery: Single-institution study.

INTRODUCTION: The extent of surgical resection for tongue tumors is determined by tumor size, potentially affecting oral function and quality of life (QoL). However, the relationship between oral dysfunction and QoL decline due to glossectomy extent remains unexplored. Therefore, these correlations and their predictive value for postoperative QoL decline were elucidated. METHODS: Patients treated for tongue cancer at our hospital between 2018 and 2022 were categorized by partial, hemi, or subtotal/total glossectomy. Assessments included swallowing function (RSST), articulation (Oral Diadochokinesis (ODK)), mastication, tongue pressure, and oral moisture. QoL was measured using the Oral Health Impact Profile-14 (OHIP-14). Differences within parameters were assessed using Kruskal-Wallis tests, and between-group comparisons via Mann-Whitney U tests. Spearman's correlation analysis examined parameter relationship. RESULTS: 35 patients were evaluated. Significant differences were found in ODK [ta] (p = 0.015), [ka] (p = 0.0006), tongue pressure (p = 0.0001), moisture levels (p = 0.031), OHIP-14 domains: physical disability (p = 0.014) and social disability (p = 0.046). ODK [ta] (PG: 5.95, HG: 5.38, TG: 4.03 times), [ka] (PG: 5.56, HG: 4.78, TG: 3.23 times), and tongue pressure (PG: 32.9, HG: 21.2, TG: 10.3 mmHg) decreased with glossectomy extent, while physical (PG: 0.27, HG: 2.38, TG: 2.00) and social disability (PG: 0.18, HG: 0.94, TG: 1.43) worsened. A significant negative correlation was observed between tongue pressure and social disability (p = 0.013, r = -0.36). CONCLUSION: Expanding resection significantly impacted postoperative oral function and QoL. Tongue pressure assessment may predict long-term social disability in patient QoL.

Current conditions and issues of physicians and working conditions at institutions accredited by the Japanese Breast Cancer Society.

BACKGROUND: In Japan, with the rapid increase of breast cancer patients, there has been increasing demand for breast cancer treatment. As the main workforce for breast cancer treatment, women physicians are thought to be in key positions, since the number of women physicians has recently been increasing. METHODS: To clarify the current statuses and issues of physicians and work conditions at the accredited breast cancer care facilities, a survey was conducted by the Japanese Breast Cancer Society (JBCS). RESULTS: The main workforces engaged in breast cancer care are surgeons, and the number of breast surgeons of all institutions in this survey was 1338 (full time 1124, part time 214). The percentages of women among surgeons, breast specialists accredited by the JBCS, and residents are 22%, 25%, and 38%, respectively. Among breast specialists, more women tended to work at university hospitals and cancer hospitals. Twenty-eight percent of women were married and among those, 76% had at least one child. Many hospitals allow short working hours or exemption from in-house call for women surgeons during pregnancy and child-rearing. In contrast, half of the facilities apply a "single doctor-in-charge system", where the patient's primary physician has to be on-call every day. Many institutions convene conferences for breast cancer treatment planning before or after the scheduled working hours. CONCLUSIONS: Current systems for treatment of breast cancer should be improved so that all surgeons specializing in the breast can develop their career while maintaining their personal life.

Hypoxia-induced HIF-1α and ZEB1 are critical for the malignant transformation of ameloblastoma via TGF-ß-dependent EMT.

Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification. AC develops pulmonary metastasis in about one third of the patients and reveals a poor prognosis. However, the mechanisms of AC oncogenesis remain unclear. In this report, we aimed to clarify the mechanisms of malignant transformation of AB or AC carcinogenesis. The relatively important genes in the malignant transformation of AB were screened by DNA microarray analysis, and the expression and localization of related proteins were examined by immunohistochemistry using samples of AB and secondary AC. Two genes of hypoxia-inducible factor 1 alpha subunit (HIF1A) and zinc finger E-box-binding homeobox 1 (ZEB1) were significantly and relatively upregulated in AC than in AB. Both genes were closely related in hypoxia and epithelial-mesenchymal transition (EMT). In addition, expressions of HIF-1α and ZEB1 proteins were significantly stronger in AC than in AB. In the cell assays using ameloblastoma cell line, AM-1, hypoxia condition upregulated the expression of transforming growth factor-ß (TGF-ß) and induced EMT. Furthermore, the hypoxia-induced morphological change and cell migration ability were inhibited by an antiallergic medicine tranilast. Finally, we concluded that hypoxia-induced HIF-1α and ZEB1 were critical for the malignant transformation of AB via TGF-ß-dependent EMT. Then, both HIF-1α and ZEB1 could be potential biomarkers to predict the malignant transformation of AB.

Nuclear PKM2 promotes the progression of oral squamous cell carcinoma by inducing EMT and post-translationally repressing TGIF2.

Pyruvate kinase M2 (PKM2), a glycolytic enzyme, acts as a metabolic function leading to an energy production critical for cancer progression, known as Warburg effect. In this study we showed a pivotal role of PKM2 acting as a non-metabolic function to promote cancer cell progression in human oral squamous cell carcinoma (OSCC) through the induction of epithelial-mesenchymal transition (EMT), which is crucial for the potential in cancer cell invasion, and post-translational TGIF2 degradation. PKM2 immunoreaction was strong in the cytoplasm of invasive cancer cells, and distinct in the nucleus of spindle-shaped cancer cells with EMT characteristics. TGIF2 nuclear immunoreaction was seen in dysplastic epithelial cells but was repressed in cancer cells. In vitro analyses, cytoplasmic expression of PKM2 was translocated into the nucleus in human OSCC derived HSC-4 and SAS cells when EMT was stimulated. In addition, nuclear expression of TGIF2 was distinctively repressed in EMT induced HSC-4 and SAS cells. We recognized a mismatch in TGIF2 protein and mRNA expression in EMT induced HSC-4 and SAS cells and found that TGIF2 protein was post-translationally degraded through a ubiquitin proteasome system by an MG132 proteasome inhibition assay. Finally, promotion of HSC-4 and SAS cell progression by PKM2 was recognized in PKM2 knockdown assays. Thus, we clarified a new mechanism of non-metabolic function of PKM2 to promote the progression of OSCC through PKM2 nuclear translocation, subsequently induced EMT, and post-translationally repressed TGIF2 expression by a ubiquitin proteasome system.

Is clinical breast examination effective in Japan? Consideration from the age-specific performance of breast cancer screening combining mammography with clinical breast examination.

BACKGROUND: There is controversy about the value of clinical breast examination (CBE) in breast cancer screening programs that include mammography. METHODS: In Fukui Prefecture, a screening combining mammography with CBE was employed on 62,447 women from 2004 to 2009. We examined the sensitivity and specificity of mammography alone, and mammography and CBE together for each age group (40-49, 50-59, 60-69, and 70-79). RESULTS: 167 breast cancers and 49 false-negative cancers were detected during 5 years. For the combined screening, the sensitivities were 73.1, 74.1, 78.3, and 86.5 %, and the specificities were 83.8, 87.5, 89.8, and 90.9 % in the groups of 40-49, 50-59, 60-69, and 70-79 years, respectively. In the mammography-specific analysis, sensitivity decreased to 69.8 % (-3.3 %), 66.7 % (-7.7 %), 77.3 % (-1.0 %), and 83.8 % (-2.7 %) in the groups of 40-49, 50-59, 60-69, and 70-79 years, respectively. There were greater reductions in the groups of 40-49 and 50-59 years than in those of 60-69 and 70-79 years, but there was no statistically significant decrease. Specificity generally increased with increasing age and there was a significant improvement in specificity among all age groups, except that of 70-79 years. CONCLUSIONS: Our findings suggest that there is a trade-off between sensitivity and specificity associated with CBE added to mammography. This tendency is greater in those 40-50 years of age than in those 60-70 years of age. We consider that CBE may be omitted from breast cancer screening among women aged 60 and 70 years. Furthermore, another modality to complement mammography screening in younger Japanese women is expected.

Effectiveness of Trivalent Inactivated Influenza Vaccine in Children Estimated by a Test-Negative Case-Control Design Study Based on Influenza Rapid Diagnostic Test Results.

We assessed vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in children 6 months to 15 years of age in 22 hospitals in Japan during the 2013-14 season. Our study was conducted according to a test-negative case-control design based on influenza rapid diagnostic test (IRDT) results. Outpatients who came to our clinics with a fever of 38 °C or over and had undergone an IRDT were enrolled in this study. Patients with positive IRDT results were recorded as cases, and patients with negative results were recorded as controls. Between November 2013 and March 2014, a total of 4727 pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was unknown; 1405 were positive for influenza B; and 2445 were negative for influenza. Overall VE was 46% (95% confidence interval [CI], 39-52). Adjusted VE against influenza A, influenza A(H1N1)pdm09, and influenza B was 63% (95% CI, 56-69), 77% (95% CI, 59-87), and 26% (95% CI, 14-36), respectively. Influenza vaccine was not effective against either influenza A or influenza B in infants 6 to 11 months of age. Two doses of influenza vaccine provided better protection against influenza A infection than a single dose did. VE against hospitalization influenza A infection was 76%. Influenza vaccine was effective against influenza A, especially against influenza A(H1N1)pdm09, but was much less effective against influenza B.

Prevalence and risk factors of bone metastasis and skeletal related events in patients with primary breast cancer in Japan.

BACKGROUND: Bone metastasis (BM) is important for studying systemic spread of breast cancer. It often causes skeletal-related events (SREs) that worsen quality of life. We investigated the prevalence and risk factors for BM and SRE using a dataset from the Breast Oncology Research Network (BORN) in Japan. PATIENTS AND METHODS: We collected data on primary breast cancer patients with node-positive or node-negative disease at intermediate to high risk of recurrence. The risk factors affecting the BM-free rate, SRE-free rate and overall survival were analyzed by using the Cox proportional hazard model. RESULTS: Data of 1,779 patients who were diagnosed with breast cancer during 2003-2005 were collected from the BORN and 1,708 cases were used for analysis. The median follow-up duration was 5.71 years. BM developed in 193 cases (11.3 %) and the BM-free rate at 5 years was 89.2 %. The annual hazard ratio of BM development differs remarkably according to the tumor subtype. SREs occurred in 133 (68.9 %) out of 193 patients and the SRE-free rate at 5 years was 92.6 %. In the multivariate analysis, clinical stage (P < 0.0001), number of lymph node (LN) metastases (P = 0.0029), tumor subtype (P = 0.034) and progesterone receptor status (P = 0.038) were independently significant risk factors for BM-free rate, but only clinical stage (P < 0.0001) and number of LN metastases (P = 0.0004) significantly correlated with SRE-free rate. CONCLUSIONS: This retrospective study clarifies the prevalence and risk factors for BM and SRE in Japanese breast cancer patients. Our results show the importance of considering subtype in the care of BM and SRE.

[A case of postoperative chestwall recurrence of gastric cancer responding to a combination of radiation, hyperthermia and oral administration of TS-1].

A 77-year-old man diagnosed with advanced gastric cancer underwent total gastrectomy with combined splenectomy and resection of the pancreatic tails in 1996. He was treated with 400 mg/day of UFT for 2 years. Serum CEA level was found to be elevated on July 5, 2001. He complained of left chest pain in December 2001. A 4 cm-sized tumor was detected in the region extending from the subcutaneous region to the left chest wall containing the osteolytic change of the left sixth rib. He was diagnosed with a chest wall metastasis from gastric cancer. He underwent radiotherapy with thermotherapy and was also treated with chemotherapy. TS-1 was administered at 80-100 mg/body/day, twice daily for 3 weeks followed by a 2-week rest interval as 1 cycle. As a results, shrinkage of the tumor was confirmed on February 14, 2002. The tumor was confirmed to have disappeared on April 17, 2002, by chest CT. A complete response of the metastatic tumor was achieved. The patient maintained a complete response for more than 12 months, but died from the chest wall metastasis recurrence and weakness on August 13, 2003. The only observed adverse event, was grade 2 leukopenia.