Multimodal Prediction of Cervical Lymph Node Metastasis and Recurrence in Oral Squamous Cell Carcinoma

Background/Aim: Oral squamous cell carcinoma (OSCC) is the most common malignancy in the head/neck region, and cervical lymph node (CLN) metastasis is a strong poor-prognosis factor. In addition, many patients with OSCC experience recurrence despite multidisciplinary treatment. We sought to identify factors associated with CLN metastasis and recurrence in patients with OSCC. Patients and Methods: We evaluated a total of 45 patients and 233 target CLNs. The longest diameter of the target CLN, the shortest diameter of the target CLN (LS), the area of the target CLN, and the relative computed tomography (CT) values of the target CLNs calculated based on the CT values of the internal jugular vein (LCT) were obtained from preoperative CT images, and the maximum standardized uptake values of the primary tumor (pSUV) and target CLN (nSUV) were obtained from preoperative 18F-fluorodeoxyglucose-positron emission tomography/CT images. We performed immunohistochemical staining for cytokeratin 13 (CK13) and 17 (CK17) on neck dissection tissues. Results: A discrimination equation was used that can predict CLN metastasis with a 92.2% discrimination rate using LS, LCT, pSUV, and nSUV. The CLNs were divided into discrimination and non-discrimination groups based on discriminant equations and CK13 and CK17 were used as the objective variables. A significantly higher recurrence rate was observed in the non-discrimination group (CK13: 5-year recurrence rate 28.6% vs. 64.3%, p<0.01; CK17: 5-year recurrence rate 28.0% vs. 76.0%, p<0.01). Conclusion: CLN metastases in OSCC can be assessed by combining preoperative imaging. The combined use of CK13 and CK17 expression with imaging findings offers an integrated approach to predict OSCC recurrence

LACTATE/MCT4/GPR81 AXIS IN BONE PAIN OF BREAST CANCER

Breast cancer (BC) bone metastasis causes bone pain (BP), which detrimentally damages the quality of life and outcome of patients with BC. However, the mechanism of BC‑BP is poorly understood, and effective treatments are limited. The present study demonstrated a novel mechanism of BC‑BP using a mouse model of bone pain, in which mouse (EO771) and human (MDA‑MB‑231) BC cells were injected in the bone marrow cavity of tibiae. Western blot analysis using sensory nerves, in vivo assessment of cancer pain and in vitro calcium flux analysis were performed. These mice developed progressive BC‑BP in tibiae in conjunction with an upregulation of phosphorylated pERK1/2 and cAMP‑response element‑binding protein (pCREB), which are molecular indicators of neuron excitation, in the dorsal root ganglia (DRG) of sensory nerves. Importantly, mice injected with BC cells, in which the expression of the lactic acid transporter monocarboxylate transporter 4 (MCT4) was silenced, exhibited decreased BC‑BP with downregulated expression of pERK1/2 and pCREB in the DRG and reduced circulating levels of lactate compared with mice injected with parental BC cells. Further, silencing of the cell‑surface orphan receptor for lactate, G protein‑coupled receptor 81 (GPR81), in the F11 sensory neuron cells decreased lactate‑promoted upregulation of pERK1/2 and Ca2+ influx, suggesting that the sensory neuro excitation was inhibited. These results suggested that lactate released from BC cells via MCT4 induced BC‑BP through the activation of GPR81 of sensory neurons. In conclusion, the activation of GPR81 of sensory neurons by lactate released via MCT4 from BC was demonstrated to contribute to the induction of BC‑BP, and disruption of the interactions among lactate, MCT4 and GPR81 may be a novel approach to control BC‑BP

Biological Differences Between Ovarian Cancer-associated Fibroblasts and Contralateral Normal Ovary-derived Mesenchymal Stem Cells

Background/Aim: The aim of this study was to clarify the biological differences between ovarian cancerassociated fibroblasts (OCa-CAFs) and normal ovary-derived mesenchymal stem cells (NO-MSCs). Materials and Methods: Surgically resected ovarian cancer and contralateral normal ovarian tissue samples were cut into small pieces for culture as “explants”. The number of outgrown cells, their proliferative kinetics, and expression levels of cell surface markers of CAFs, as well as three miRNAs in OCa-CAFs and NO-MSCs were compared directly. Differentially expressed genes between both groups were also investigated. Results: Comparable numbers of outgrown cells were harvested from both groups. Significantly higher expression of α-smooth muscle actin and miR-142 was found in OCa-CAFs, which decreased significantly during ex vivo cell expansion. A total of 21 differentially expressed genes were identified between both groups. Conclusion: OCa-CAFs showed different biological properties in direct comparison with NO-MSCs, which might play major roles in the pathogenesis of ovarian cancer

High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer

Advanced head and neck cancer (HNC) can invade facial bone and cause bone pain, thus posing a significant challenge to the quality of life of patients presenting with advanced HNC. The present study was designed to investigate HNC bone pain (HNC‑BP) in an intratibial mouse xenograft model that utilized an HNC cell line (SAS cells). These mice develop HNC‑BP that is associated with an expression of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in dorsal root ganglia (DRG) sensory neurons. Our experiments demonstrated that the inhibition of high mobility group box 1 (HMGB1) by short hairpin (shRNA) transduction, HMGB1 neutralizing antibody, and HMGB1 receptor antagonist suppressed the HNC‑BP and the pERK1/2 expression in DRG. It was also observed that HNC‑derived HMGB1 increased the expression of the acid‑sensing nociceptor, transient receptor potential vanilloid 1 (TRPV1), which is a major cause of osteoclastic HNC‑BP in DRG. Collectively, our results demonstrated that HMGB1 originating in HNC evokes HNC‑BP via direct HMGB1 signaling and hypersensitization for the acid environment in sensory neurons

Prognostic Factors in Endodontic Surgery Using an Endoscope: A 1 Year Retrospective Cohort Study

This retrospective study clarified the success rate of endoscopic endodontic surgeries and identified predictors accounting for successful surgeries. In this retrospective study, 242 patients (90 males, 152 females) who underwent endoscopic endodontic surgery at a single general hospital and were diagnosed through follow-up one year later were included. Risk factors were categorized into attributes, general health, anatomy, and surgery. Then, the correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and factors related to the surgical prognosis factor were identified. The success rate of endodontic surgery was 95.3%, showing that it was a highly predictable treatment. The top three correlation coefficients were post, age, and perilesional sclerotic signs. Among them, the presence of posts was the highest, compared with the odds ratio, which was 9.592. This retrospective study revealed the success rate and risk factors accounting for endoscopic endodontic surgeries. Among the selected clinical variables, the presence of posts was the most decisive risk factor determining the success of endodontic surgeries

Clinical Indication of Laparoscopic Surgery for Colorectal Cancer: The Optimal Extent of Lymph Node Dissection based on Depth of Colorectal Cancer and Technical Feasibility of Laparoscopic Colorectal Surgery.

Recently, laparoscopic colorectal surgery has been considered to be appropriate for colorectal cancer, and the feasibility of many laparoscopic techniques has been established; however, the indication for curative colorec-tal cancers is controversial. In this study, before laparoscopic procedure was performed on patients with colorectal cancers, 641 patients who had under-gone open laparotomy for colorectal cancer during the past 16 years were ev-aluated for the distribution of metastatic lymph nodes classified by depth of invasion. The results obtained were as follows: The rate of all lymph node metastasis of patients with pTis was 0%. The rate of intermediate lymph node (n2) metastasis of patients with pT1 and pT2 tumor was low (3.4% and 4.1% respectively) , however, in patients with pT3 and pT4 tumors, this rate was much higher (15.9% and 15.8% respectively) . Therefore, with re-gard to lymph nodes dissection for colorectal cancer it might be concluded that the intermediate lymph nodes metastases in patients with pT1 and pT2 tumors (less than 5%) were negligible. However, in patients with pT3 and pT4 tumors, for the purpose of performing a complete harvest of intermedi-ate lymph nodes, D3-dissection (including principal lymph node dissection) is required. it is questionable whether or not performance of the laparoscopic procedure for cancer achieves the same extent of lymph node dissection as compared with open laparotomy. Dissection was restricted to intermediate grade lymph node including the paracolic lymph nodes (D2) . Accordingly, patients with pT3 and pT4 tumor should be excluded from indication for laparoscopic procedure. Between October 1997 and November 1998, laparoscopic colorectal resec-actions were performed on a limited number of the above mentioned patients with Tis, Ti and T2 tumor. The grade of lymph node dissection was deter-mined by the results of a preoperative assessment of the depth of cancer in-vasion. With the exception of one patient, whose preoperative assessment for depth of cancer invasion was a limitation at the muscularis propria, but whose histological outcome had been pT3 tumor, all the other patients were able to undergo laparoscopic colorectal resection. The final histological results were as follows: 3 patients with pTis tumor, 6 pTl tumor, and 3 pT2 tumor. One of the pT3 patients alone was converted from a laparoscopic pro-cedure to open laparotomy because of the intraoperative proof of intermediate lymph node metastases, and subsequently this patient underwent principal lymph node dissection (D3-dissection) . With regard to the histological metas-tasis of harvested lymph nodes, no patients was found to have regional lymph node metastasis except for one patient only who had a pT3 tumor. Thus the histological findings were similar to those for conventional open laparotomy. In this study, it was concluded that by laparoscopic procedure a safe and complete dissection of intermediate lymph nodes including the paracolic lymph nodes (nl and n2) could be achieved. On the other hand, the true incidence of port site recurrence, and also its mechanism remain unknown to date. However, it is considered that the incidence of port site recurrence in patients with serosal invasion (T4 tumor) is higher than in those without (i.e., patients with pTis, pTl, pT2 and pT3 tumor) . We are also convinced that a number of patients with pTis, pTl and pT2 undergoing laparoscopic procedure were able to gain curative colorectal resection in terms of port site non-recurrence, and strongly believe that the application of laparoscopic col-orectal surgery for cancer might be acceptable

Incidence and Risk of Anti-Resorptive Agent-Related Osteonecrosis of the Jaw after Tooth Extraction: A Retrospective Study

Bone-modifying agents (BMA) such as bisphosphonates and denosumab are frequently used for the treatment of bone metastases, osteoporosis, and multiple myeloma. BMA may lead to anti-resorptive agent-related osteonecrosis of the jaw (ARONJ). This study aimed to clarify the risk factors for and probabilities of developing ARONJ after tooth extraction in patients undergoing BMA therapy. In this study, the records of 505 target sites of 302 patients undergoing BMA who presented with mandibular fractures at the Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital, from March 2014 to January 2022, were retrospectively analyzed for the onset of ARONJ after tooth extraction. The following variables were investigated as attributes: anatomy, health status, and dental treatment. The correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and the factors related to the onset of ARONJ were identified. The incidence rate of ARONJ was found to be 3.2%. Hypoparathyroidism was an important factor associated with ARONJ development. Thus, systemic factors are more strongly related to the onset of ARONJ after tooth extraction than local factors

The Effectiveness of Pre-Operative Screening Tests in Determining Viral Infections in Patients Undergoing Oral and Maxillofacial Surgery

We analyzed the rate of patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection diagnosed by pre-operative screening and estimated its cost. We retrospectively analyzed patients who underwent elective surgery at our maxillofacial surgery department between April 2014 and March 2022. We compared the number of patients with each infection identified by pre-operative screening and a pre-operative questionnaire. We also compared the prevalence of infections with varying age, sex, and oral diseases, and calculated the cost of screening per positive result. The prevalence of HBV, HCV, and HIV was 0.39% (62/15,842), 0.76% (153/15,839), and 0.07% (10/12,745), respectively. The self-reported rates were as follows: HBV, 63.4% (26/41); HCV, 50.4% (62/123); HIV, 87.5% (7/8). Differences in sex were statistically significant for all infectious diseases; age significantly affected HBV and HCV rates. There was no association between the odds ratio of oral disease and viral infections. The cost per positive result was $1873.8,$905.8, and $11,895.3 for HBV, HCV, and HIV, respectively. Although self-assessment using questionnaires is partially effective, it has inadequate screening accuracy. Formulating an auxiliary diagnosis of infectious diseases with oral diseases was challenging. The cost determined was useful for hepatitis, but not HIV