Definitive internal fracture fixation followed by staged free flap coverage ("fix followed by flap" protocol) for open Gustilo type IIIB fractures.

BACKGROUND: Although the concept of the "fix and flap" approach, in which definitive fracture fixation and flap coverage are completed in a single procedure at the earliest opportunity may seem ideal for the treatment of Gustilo type IIIB open fractures, the individual circumstances of patients, such as polytrauma or multiple fracture cases may not allow for the immediate fracture fixation and flap coverage ("fix and flap" approach). In our hospital, patients with Gustilo type IIIB open fractures are treated with definitive internal fixation of the fracture followed by staged flap coverage ("fix followed by flap" protocol) when the "fix and flap" approach was not feasible due to the patient's condition or difficulty in coordinating surgery schedules. The "fix followed by flap" protocol provides benefits in terms of flexibility in adjusting the surgical timetable, simplifying the planning of flap coverage following fracture fixation, and minimizing individual surgical invasion. METHODS: We reviewed 10 cases of severe open fractures treated with the "fix followed by flap" protocol and evaluated their outcomes. All surgical procedures, including wound debridement, fracture fixation, and flap coverage, were performed by orthoplastic surgeons specializing in both fracture surgery and microsurgery including soft tissue reconstruction. RESULTS: All free flaps survived, and no partial necrosis was observed. None of the patients developed postoperative deep infection up to the last follow-up. Fracture union was achieved in all patients with or without autologous bone grafts. The median time for union was 9.4 months (range, 4-12 months). CONCLUSIONS: This study presents favorable outcomes of treatment for Gustilo type IIIB open fractures with fracture fixation followed by staged flap coverage ("fix followed by flap" protocol). Despite a delay in flap coverage, the consistency of treatment provided by orthoplastic surgeons may have contributed to the favorable outcomes in this study.

Metastatic gallbladder cancer presenting as numb chin syndrome: A case report and literature review.

Gallbladder cancer (GBC) is an uncommon malignancy that is highly aggressive in the advanced stages. However, it rarely metastasizes to the mandible. Numb chin syndrome (NCS) is a rare neurological manifestation associated with various underlying causes, including occult primary cancers and distant metastases. It is often considered to be a significant indicator of malignancy, and thorough investigation is essential in the presence of unclear etiology. The current study reported on the case of a 69-year-old Japanese woman who presented with numbness and mild pain in the lower lip and chin area for three months. No other systemic symptoms were observed. Immunocytochemical examination revealed the presence of an adenocarcinoma and TNM staging as per the Union for International Cancer Control and the American Joint Committee on Cancer guidelines confirmed stage IVb GBC. Comprehensive full-body positron emission tomography-computed tomography examination using 18F-fluoro-2-deoxy-D-glucose revealed additional bone and soft-tissue metastases. Palliative chemotherapy and radiation treatment were initiated based on the advanced stage of disease at the time of diagnosis. However, the patient succumbed to multiple organ failure six months later. The simultaneous occurrence of GBC, mandibular metastasis and NCS is rare and associated with poor prognosis. Despite the widespread nature of the disease, it can often manifest as non-specific oral symptoms without any systemic indications. The current study emphasizes the critical importance of timely confirmatory testing for accurate diagnosis and initiation of appropriate management for such complex conditions.

Efficacy of an enhanced recovery after surgery pathway to manage pain, nausea and vomiting after head and neck surgeries with free tissue transfer reconstruction.

BACKGROUND: Pain and post-operative nausea and vomiting are the main factors that impair the quality of recovery after surgery. Very few reports have analyzed patient-reported outcomes to investigate the efficacy of an enhanced recovery after surgery protocol to alleviate these symptoms after head and neck surgeries with free tissue transfer reconstruction. METHODS: We investigated post-operative pain and post-operative nausea and vomiting in 47 patients who underwent head and neck surgeries with free tissue transfer reconstruction with enhanced recovery after surgery support between February 2021 and August 2022. Patient-reported outcomes were assessed using the visual analog scale and Japanese version of the Quality of Recovery-40. RESULTS: Significant increases in the mean visual analog scale scores for pain and post-operative nausea and vomiting were observed only on post-operative Day 1 compared with preoperative values (pain: 3.19 ± 2.78 vs. 1.96 ± 2.42, P = 0.0408; post-operative nausea and vomiting: 1.52 ± 2.09 vs. 0.54 ± 1.37, P = 0.0194). From post-operative Day 2, there were no significant differences between the pre- and post-operative visual analog scale scores, and no significant increases in the incidences of moderate or severe pain and post-operative nausea and vomiting compared with preoperatively. The Japanese version of the Quality of Recovery-40 score for post-operative pain showed no significant deterioration compared with preoperatively, while the Japanese version of the Quality of Recovery-40 score for post-operative nausea and vomiting showed significant deterioration compared with the preoperative value on post-operative Days 2, 4 and 7. CONCLUSIONS: The visual analog scale and Japanese version of the Quality of Recovery-40 scores for post-operative pain and visual analog scale score for post-operative nausea and vomiting suggested that the enhanced recovery after surgery strategy favorably controlled pain and post-operative nausea and vomiting after head and neck surgeries with free tissue transfer reconstruction. However, as the post-operative Japanese version of the Quality of Recovery-40 score for post-operative nausea and vomiting was lower than the preoperative value, there is still a need for further improvement of the enhanced recovery after surgery pathway.

Exploring olfactory receptor family 7 subfamily C member 1 as a novel oral cancer stem cell target for immunotherapy.

The mortality rate of oral cancer has not improved over the past three decades despite remarkable advances in cancer therapies. Oral cancers contain a subpopulation of cancer stem cells (CSCs) that share characteristics associated with normal stem cells, including self-renewal and multi-differentiation potential. CSCs are tumorigenic, play a critical role in cancer infiltration, recurrence, and distant metastasis, and significantly contribute to drug resistance to current therapeutic strategies, including immunotherapy. Cytotoxic CD8+ T lymphocytes (CTLs) are key immune cells that effectively recognize peptide antigens presented by the major histocompatibility complex class I molecules. Increasing evidence suggests that cancer antigen-specific targeting by CTLs effectively regulates CSCs that drive cancer progression. In this study, we utilized data from public domains and performed various bioassays on human oral squamous cell carcinoma clinical samples and cell lines, including HSC-2 and HSC-3, to investigate the potential role of olfactory receptor family 7 subfamily C member 1 (OR7C1), a seven transmembrane G-protein-coupled olfactory receptor that is also expressed in nonolfactory tissues and was previously reported as a novel marker and target of colon cancer initiating cell-targeted immunotherapy, in CSC-targeted treatment against oral cancer. We found that the OR7C1 gene was expressed only in oral CSCs, and that CTLs reacted with human leukocyte antigen-A24-restricted OR7C1 oral CSC-specific peptides. Taken together, our findings suggest that OR7C1 represents a novel target for potent CSC-targeted immunotherapy in oral cancer.

Postoperative serum interleukin-6 level as a risk factor for development of hyperactive delirium with agitation after head and neck surgery with free tissue transfer reconstruction.

OBJECTIVE: Occurrence of hyperactive postoperative delirium (POD) with agitation after head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) is associated with the risk of life-threatening complications. The relationships between occurrence of hyperactive POD after HNS-FTTR and inflammatory markers reflecting the surgical stress response, represented by postoperative interleukin-6 levels, are not fully understood. METHODS: A retrospective study was conducted on 221 consecutive patients who underwent HNS-FTTR at our department between September 2016 and December 2021. Potential risk factors for POD were examined, including age, operation time, intraoperative blood loss, and postoperative serum levels of blood parameters such as interleukin-6, C-reactive protein, and neutrophil-to-lymphocyte ratio. RESULTS: Hyperactive POD with agitation was observed in 54 subjects (24.4%). The postoperative hospital stay in the POD group was significantly longer than that in the non-POD group (median: 32.5 days vs. 28 days; p=0.0129). Multivariate logistic regression analysis identified age (in years) (odds ratio: 1.102; p<0.0001), operation time (min) (odds ratio: 1.004; p=0.0359), and postoperative serum interleukin-6 level (pg/mL) (odds ratio: 1.005; p=0.0384) as significant risk factors for development of POD. In a receiver operating characteristic curve and area under the curve analysis, the cut-off value for postoperative serum interleukin-6 level to predict POD development was 82.5 pg/mL. The postoperative serum interleukin-6 ≥82.5 pg/mL group developed hyperactive POD with agitation significantly more often than the postoperative serum IL-6 <82.5 pg/mL group (odds ratio: 4.400; p<0.0001). The postoperative serum IL-6 ≥82.5 pg/mL group also had significantly longer postoperative hospital stay (41.58 ± 33.42 days vs. 31.73 ± 22.89 days; p=0.0151), older age (68.60 ± 9.99 years vs. 64.30 ± 12.58 years; p=0.0054), and longer operation time (625.4 ± 114.05 min vs. 575.5 ± 98.73 min; p=0.0009) than the postoperative serum IL-6 <82.5 pg/mL group. CONCLUSION: Postoperative serum interleukin-6 level, as well as age and operation time, were identified as significant independent risk factors for development of hyperactive POD with agitation after HNS-FTTR. Inflammation is a potential target for the prevention and treatment of POD after HNS-FTTR.

Odontogenic keratocyst in the mandibular condyle base region: A case report.

Odontogenic keratocysts (OKCs) often occur in the molars in the mandibular ramus; they often progress asymptomatically and are discovered only after widespread development. Some cases of OKC progress to the mandibular condyle; however, very few cases exist only in the condyle. To the best of our knowledge, in all of the previously reported cases, OKCs occurred in the mandibular ramus, which underwent resection. The present study reports the case of a 31-year-old man in whom an OKC (13x12x6 mm) occurred discretely in the base of the condyle, in which the condylar head was successfully preserved. The tumor was removed under general anesthesia using the approach of shaving the anterior surface of the mandible. The extraction cavity was managed using the packed open technique and with an obturator. Approximately 20 months post-operation, the patient remained recurrence-free. This report presents a rare case of an OKC in the mandibular condyle base region. Resection was performed under general anesthesia and the condylar process was successfully preserved.

Preoperative serum interleukin-6 level in head and neck cancer reflects systemic inflammatory response and is a predictor of postoperative prognosis.

BACKGROUND: The outcome of head and neck cancer has improved in recent years but survival is not yet satisfactory. Interleukin (IL)-6 is a representative inflammatory cytokine and inducer of systemic inflammatory response. It is not known whether preoperative serum level of IL-6 is a prognostic factor in head and neck cancer surgery. METHODS: We studied 181 consecutive patients who underwent head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) between September 2016 and December 2020. Whether preoperative serum IL-6 level was a prognostic risk factor was retrospectively investigated by univariate and multivariate analyses. We also investigated the association between preoperative IL-6 level and representative systemic inflammatory response markers. RESULTS: The preoperative IL-6 ≥ 8 pg/mL group had a significantly worse prognosis than the preoperative IL-6 < 8 pg/mL group (overall survival [OS]: hazard ratio [HR] 3.098, P = 0.0006; disease-specific survival [DSS]: HR 3.335, P = 0.0008). In multivariate analysis, IL-6 ≥ 8 pg/mL and age ≥ 70 years were independent poor prognostic factors for OS (HR 1.860, P = 0.0435 and HR 1.883, P = 0.0233, respectively). The only independent poor prognostic factor for DSS was IL-6 ≥ 8 pg/mL (HR 2.052, P = 0.0329). Serum albumin was significantly lower and serum C-reactive protein and neutrophil-to-lymphocyte ratio were significantly higher in the IL-6 ≥ 8 pg/mL group than in the IL-6 < 8 pg/mL group (all P < 0.0001). CONCLUSIONS: Preoperative serum IL-6 level is an independent poor prognostic factor for both OS and DSS after HNS-FTTR, reflecting the degree of preoperative systemic inflammatory response.

Study protocol of brief intervention using gene polymorphism information for excessive drinking among Japanese college students and adults aged 20-30 years: a randomized controlled trial.

BACKGROUND: The alcohol-metabolizing enzyme aldehyde dehydrogenase 2 (ALDH2) is a carcinogenic acetaldehyde-degrading enzyme, and its low activity is a genetic constitution peculiar to East Asians. People with low alcohol dehydrogenase 1B activity (ADH1B*1/*1 genotype) have a high risk of developing head and neck cancer and alcoholism. The study aims to evaluate the effectiveness of brief interventions for excessive drinking among college students and adults in their 20s, including information on five constitutions that combine the ALDH2 and ADH1B genotypes. METHODS: Participants comprised university students and staff aged 20-30 years who had consumed ≥40 g (males) or ≥20 g (females) of pure alcohol; they were classified into intervention and control groups using a simple randomization method. Participants anonymously filled out questionnaires linked to identification numbers and recorded the drinking days and amounts on the drinking calendar. The intervention group will then be tested for genotype testing using saliva (5 types of combinations of ALDH2 and ADH1B enzyme activities); the result report will arrive approximately 1 month later. We will conduct a 30-min face-to-face or online intervention. The control group will be merely given the conventional materials, and genetic testing will be performed voluntarily after 6 months (end of study). The intervention group will undergo questionnaire surveys 1 month after the intervention and 3 and 6 months after baseline. Questionnaire surveys will be conducted 1, 3, and 6 months after baseline for the control group. The average amount of drinking before and after the intervention, attribute/baseline data between the two groups, and time-series data were compared using various analysis tools. For interventions, we engaged in dialog based on intervention materials that added genotyping content to the existing materials, result reports, baseline data, and drinking calendar records. Participants' ingenuity is respected to support their drinking behavior and goal setting. DISCUSSION: Individual information on the genetic makeup of alcohol-metabolizing enzymes provided during the intervention is more personal and objective than general health information, especially in Japan, where the ALDH2 low activity rate is high. This information may be useful for health care and precautionary measures. TRIAL REGISTRATION: R000050379, UMIN000044148, Registered on June 1, 2021. Scientific Title: Examination of simple intervention using genetic polymorphism information for excessive drinking.

An unusual case of oral surgical management in a patient with isovaleric acidemia and schizophrenia: A case report.

Oral/dental surgical care in patients with chronic medical comorbidities, such as isovaleric acidemia (IVA), can be challenging. In addition to technical complications, different comorbidities also present a complex range of concerning factors/challenges, which can increase the incidence of morbidity and mortality associated with surgery. IVA, a congenital error of metabolism, is a rare organic acidemia with a predisposition towards acute acidosis and life-threatening metabolic decompensation during stressful conditions, such as prolonged fasting and surgery. In addition, schizophrenia, a major neurological disorder, can result in manifestation of severe dental or periodontal conditions, including pericoronitis. The condition is associated with significant risk factors of postoperative complications, such as dangerous behaviors and adverse interactions between antipsychotic drugs and anesthetic agents. A case of comorbid dental disease with two coexisting chronic and life-threatening medical conditions, one of which is rare, is an unusual encounter in oral/dental surgery that is seldomly published. Moreover, implementing a safe and effective surgical intervention in such patients requires several informed considerations. However, only a few reported experiences or guidelines exist, reporting appropriate perioperative management strategies to minimize risks. Hence, in this case report, our experience of managing one of these rare encounters of a 20-year-old man who suffered from bilaterally partially erupted third molars, associated with chronic pericoronitis and dental caries of both the maxilla wisdom teeth with coexisting IVA and schizophrenia comorbidities is described. Additionally, the presentation and anticipated complications of the comorbid disorders of the patient are briefly reviewed. In this case, the pericoronitis and dental caries were treated by surgically removing the impacted third molars and the antagonist maxilla wisdom teeth under regional anesthesia and application of antibiotics for 3 days. The patient recovered without any postoperative complications after 1 year of follow-up.

Neck dissection with carotid artery resection after insertion of a protective endovascular covered stent for recurrent head and neck cancer: a case report.

Head and neck cancer involving the carotid artery is usually unresectable. Such involvement often leads to exposure of the carotid artery and the risk of its blow-out. Carotid covered stent placement may be effective in preventing carotid blow-out; however, thus far, there are few published reports of this procedure. We here present a 65-year-old man who developed neck node recurrence of laryngeal cancer involving the carotid artery, which eventually resulted in exposure of that artery and its impending blow-out. A balloon occlusion test was performed to confirm that the circle of Willis was complete. A covered stent was inserted simultaneously into the affected carotid, enabling us to perform en block resection of the tumor and involved carotid artery as an elective procedure. The patient remained alive and disease-free with no complications or sequelae 10 years after this operation. Despite carotid blow-out being considered imminent, insertion of an endovascular covered stent into the affected carotid artery allowed us to investigate the feasibility of carotid resection while simultaneously preventing that artery's rupture. Aggressive surgical resection may lead to maintenance of quality-of-life and long-term survival in selected patients.

Early enteral nutrition after head and neck surgery with free tissue transfer reconstruction.

OBJECTIVE: Early enteral nutrition is essential for enhancing recovery after surgery. However, to date, no detailed study has been conducted on the feasibility of early enteral nutrition in patients undergoing head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) and the risk factors for difficulty with early enteral nutrition. METHODS: We retrospectively analyzed 102 patients who underwent HNS-FTTR at our institution; 61 underwent free jejunal reconstruction (FJ) and 41 did not. We investigated the achievement of early enteral nutrition within 24 and 48 h after surgery and the discontinuation of enteral nutrition after its initiation within 7 days after surgery. RESULTS: Enteral nutrition could be started in 81/102 (79.4%) and 99/102 (97.1%) patients within 24 and 48 h, respectively. Cases of difficulty with early enteral nutrition accounted for 21/102 (20.6%) patients. The multivariate analysis revealed that FJ was a significant independent risk factor for difficulty with early enteral nutrition (odds ratio: 4.054, P = 0.042). The risk factors for difficulty with early enteral nutrition in patients who underwent FJ were also investigated, and the multivariate analysis showed that blood loss of ≥158 mL was a significant independent risk factor (odds ratio: 3.505, P = 0.044). CONCLUSIONS: Early enteral nutrition seemed to be provided with no problems in patients without FJ. FJ was a significant risk factor for difficulty with early enteral nutrition. Increased intraoperative blood loss was a significant risk factor for difficulty with early enteral nutrition in patients undergoing FJ; therefore, patients' abdominal symptoms and gastric residual volume should be carefully monitored in such cases.

Systemic inflammation response index (SIRI) as a predictive factor for overall survival in advanced soft tissue sarcoma treated with eribulin.

BACKGROUND: Eribulin is a tubulin and microtubule-targeting drug that has clinical benefit in overall survival (OS) for patients with advanced soft tissue sarcoma. Eribulin's efficacy has been confirmed in several clinical trials, although no clinically useful biomarkers have been identified. We therefore sought to clarify the predictive factor of eribulin treatment, while focusing on systemic inflammation and immune response values. METHODS: This study included 33 advanced STS patients treated with eribulin between March 2016 and September 2019. We evaluated the associations of clinical factors influencing the efficacy of eribulin treatment and systemic inflammatory and immune response, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the systemic inflammation response index (SIRI), and the prognostic nutrition index (PNI), with progression-free survival (PFS) and OS using the Kaplan-Meier method and log-rank test. RESULTS: NLR, LMR, PLR, SIRI, and PNI were unassociated with PFS. Compared with patients with SIRI <1.5, those with an SIRI ≥1.5 had a significantly shorter OS [median OS 15 months (95% confidence interval [CI] 8-not reached) vs. 7 months (95% CI 3-14), P = 0.04]. Moreover, the PFS tended to be shorter for patients with SIRI ≥1.5 who received chemotherapy after eribulin treatment than in those with SIRI >1.5 [median PFS 92.5 days (95% CI 27-204) vs. 133 days (95% CI 36-507), P = 0.08]. CONCLUSIONS: High SIRI values may predict poorer overall survival and the efficacy of subsequent drugs after eribulin treatment among patients with advanced soft tissue sarcoma.

Dissection of Cervical Lymph Node Metastasis With Internal Jugular-Subclavian Venous Junction Invasion Via an Approach Involving Resection of the Margin of the Medial Clavicle.

We report here a patient with a massive lymphatic metastasis involving the internal jugular-subclavian venous (IJ-SCV) junction that was safely resected with a new surgical procedure without significant complications. The patient, a 57-year-old man, had advanced hypopharyngeal cancer that had metastasized to the left IJ-SCV junction with a considerable invasion of the vessels, seemingly precluding a conventional surgical intervention. We, therefore, devised a new minimally invasive surgical approach involving resection of the margin of the medial clavicle, which provided an open view of the operation field. This enabled severance of both subclavicular and brachiocephalic veins and removal of the tumor. All procedures were accomplished safely and there were no postoperative circulatory disturbances, including arm edema and compartment syndrome, in the ipsilateral arm. Additionally, postoperative adjuvant chemoradiotherapy was completed uneventfully.

[Renal Cell Carcinoma in the Left Pelvic Kidney : A Case Report].

We report the case of a 61-year-old man who was incidentally diagnosed with a left pelvic ectopic kidney with renal tumor. Computed tomography showed a hypervascular tumor at the posterior surface of the ectopic kidney with five arterial and two venous supply vessels. On preoperative examination, this patient had respiratory dysfunction. For these reasons, an open radical nephrectomy was performed. Histological examination revealed a clear cell renal cell carcinoma, pT1aN0M0, G1, and a Fuhrman nuclear grading system grade of G2. No evidence of disease was observed 15 months after surgery.

Radiation Dose Reduction for Computed Tomography Localizer Radiography Using an Ag Additional Filter.

OBJECTIVE: This study aimed to assess the potential of an Ag additional filter attached to the bow tie filter of a computed tomography (CT) scanner to reduce the radiation dose in CT localizer radiography. METHODS: Radiation doses in CT localizer radiography with Cu and Ag additional filters were evaluated based on dose measurements and Monte Carlo simulations. Image quality evaluations of an adult torso phantom were performed, and the automatic exposure control performance was evaluated in terms of the water-equivalent thickness estimated from CT localizer radiographs. RESULTS: With the Ag additional filter, effective doses were approximately 72% to 75% lower than those with the Cu additional filter. The image quality and water-equivalent thickness with the Ag additional filter were similar to those with the Cu additional filter. CONCLUSIONS: The Ag additional filter helped significantly reduce radiation doses in CT localizer radiography while maintaining image quality and performance.

Prognosis and surgical outcome of soft tissue sarcoma with malignant fungating wounds.

OBJECTIVE: Malignant fungating wounds are ulcerating tumors that infiltrate the overlying skin. Little evidence exists regarding the prognosis or treatment of malignant fungating wound in soft tissue sarcoma. This study aimed to reveal the prognosis and outcome of surgical treatment of malignant fungating wound in soft tissue sarcoma. METHODS: We retrospectively reviewed 26 patients with malignant fungating wound in high-grade soft tissue sarcoma between 2005 and 2018. The patients' characteristics, treatments, surgical wound complications, local recurrences and prognoses were analyzed. Overall survival was analyzed using the Kaplan-Meier method and compared with that of the control cohort, consisting of 236 consecutive patients with non-malignant fungating wound high-grade soft tissue sarcoma treated during the same period. RESULTS: Among the 26 patients, undifferentiated pleomorphic sarcoma was the most common subtype. Twenty-three patients, including 20 (87%) and 3 (13%), underwent limb-salvage surgery and amputation, respectively. Among the 20 patients who underwent limb-salvage surgery, 4 (20%) had surgical wound complications, which required additional surgical procedures. Excluding the patients who underwent palliative surgery, local recurrence occurred in 2 patients (11%). The 5-year overall survival rate for all high-grade malignant fungating wound and non-malignant fungating wound patients was 26.0 and 67.3% (P < 0.0001), respectively. CONCLUSIONS: Malignant fungating wounds in soft tissue sarcoma were significantly associated with a poor prognosis; however, the incidence of surgical complications and local recurrence after limb-salvage surgery was comparable to that of general soft tissue sarcoma cases. Limb-salvage surgery should be considered, if possible, to preserve the patient's quality of life because of the dismal prognosis of patients with malignant fungating wound in soft tissue sarcoma.

Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumor (MPNST) often does not respond well to chemotherapy and develops against a background of NF1. The purpose of our study was to examine the efficacy of pazopanib against MPNST. Our study was designed as a physician-initiated phase II clinical trial in patients with advanced MPNST. Patients were registered from 11 large hospitals. The primary endpoint was set to clarify the clinical benefit rate (CBR) at 12 weeks according to response evaluation criteria in solid tumors (RECIST). Progression-free survival (PFS), overall survival (OS) and the CBR based on modified Choi evaluation at week 12 were set as secondary endpoints along with treatment-related safety. The study enrolled 12 patients. Median age was 49 years. Seven had Grade 2 and five Grade 3 according to the FNCLCC evaluation. Median follow-up period was 10.6 months. CBR at 12 weeks was both 50.0% (RECIST and Choi). The median PFS was 5.4 months for both RECIST and Choi, and the median OS was 10.6 months. Of special interest, the median PFS was 2.9 months for patients with FNCLCC Grade 2 and 10.2 months for Grade 3 (both RECIST and Choi). Grade 4 adverse events of neutropenia and lipase elevation were noted in one patient each. The results of this pazopanib therapy were generally better than those of any of the other single molecular targeted therapies reported previously. Although accumulation of more cases remains necessary, we conclude pazopanib treatment for MPNST to be a safe and promising treatment after doxorubicin-based chemotherapy.

Pretreatment serum C-reactive protein is a significant prognostic factor in patients with soft tissue metastases.

BACKGROUND: Soft tissue metastasis is rarer than bone metastasis. Patients with soft tissue metastasis generally have a dismal prognosis. The treatment for metastatic lesions is sometimes difficult, because the prognostic factors of patients with soft tissue metastasis remain unelucidated. Therefore, this study aimed to identify these prognostic factors. METHODS: Thirty-one patients with soft tissue metastasis were included in the study. We evaluated associations of overall survival with clinical parameters and inflammatory markers using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Twelve patients received surgery for soft tissue metastasis, while radiation therapy was performed in six cases. The median overall survival after the detection of soft tissue metastasis was 11 months. Univariate analysis revealed that detection of soft tissue metastasis after the multidisciplinary treatment (P = 0.01); solitary metastasis (P = 0.0003); and pretreatment C-reactive protein (CRP) level < 0.4 mg/dL (P < 0.0001), white blood cell count < 8500 × 103/µL (P = 0.0003), and neutrophil-to-lymphocyte ratio < 5 (P = 0.02) were significant good prognostic factors. Multivariate analysis revealed that a CRP value < 0.4 mg/dL (P = 0.07) and solitary metastasis (P = 0.09) were possible significant predictors of survival. Furthermore, in case of CRP levels <0.4 mg/dL and metastatic tumor resection, patients had a good prognosis; however, when the CRP levels increased to 0.4 mg/dL and above, patients had a poor prognosis, irrespective of tumor resection. CONCLUSIONS: CRP is potentially useful for determining the indication of radical metastasectomy in soft tissue metastasis.

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.

Applications of a grid-based CYP3A4 Template system to understand the interacting mechanisms of large-size ligands; part 4 of CYP3A4 Template study.

Catalytic interactions of CYP3A4 with large-size ligands have been studied on the Template established in our previous studies using polyaromatic hydrocarbon and steroid ligands (DMPK 34: 113-125 and 351-364 2019 and in press 2020). Typical CYP3A4-substrates including erythromycin, cyclosporin A (ca.1200 Da), ivermectin B1a and taxanes were applied successfully and regioselective metabolisms of these ligands were reconstituted faithfully on Template. These results suggest the applicability of CYP3A4 Template throughout broadened sizes of CYP3A4 ligands. Macrolide antibiotics showed distinct degrees of tight sittings in Width-gauge, a tool for accommodation measure. The observed differences were associated with different inhibitory/inactivation potentials of troleandomycin, erythromycin, clarithromycin and azithromycin, suggesting CYP3A4 Template also as a tool for drug-interaction mechanisms. Slight expansion of Template area was made at near Site of oxidation from simulation results of antitumor agent, rilpivirine, in the present study. Ligand entry from left side of Template is also suggested from macrolide interactions. Broadened applicability of the refined CYP3A4 Template were assured with experiments with various large-size ligands.