Effect of scission on alignment of nonionic surfactant micelles under shear flow.

We investigate the alignment of wormlike micelles under shear flow with dissipative particle dynamics simulations of nonionic surfactant solutions. To reveal the effect of micellar scission on alignment, we evaluate the shear-rate dependence of the mean orientation angle and the average lifetime of micelles for fixed aggregation numbers. Our numerical results demonstrate the presence of two distinct shear-rate regimes of micellar alignment. In the low shear-rate regime, where flow-induced scission does not occur, wormlike micelles align more in the flow direction with the shear rate. In contrast, flow-induced scission suppresses micellar alignment in the high shear-rate regime. In addition, comparing the alignment of wormlike micelles with that of polymers without scission, we find that the mean orientation angle of wormlike micelles is larger than that of polymers when flow-induced scission occurs. This comparison confirms that flow-induced scission yields the unique behavior of micellar alignment. Furthermore, we demonstrate that flow-induced scission suppresses micellar alignment for fixed aggregation numbers by reducing the effective longest relaxation time of micelles.

Recombination statistics of nonionic surfactant micelles at equilibrium.

We conduct dissipative particle dynamics simulations of nonionic surfactant solutions to investigate the statistical properties of micellar recombination. We categorize the recombination events into self-recombination, where two micelles created by scission join together, and non-self-recombination. We find that these two recombination events exhibit distinct statistical properties. The probability density function of the recombination time for self-recombination follows a power law, and we show that the mean squared displacement of the surfactants determines the exponent of the power law. In contrast, the survival function for non-self-recombination is exponential, which is consistent with the mean-field model. For non-self-recombination, we evaluate the mean recombination time for various aggregation numbers, temperatures, and surfactant volume fractions. We find a scaling law describing the mean recombination time of the micelles at equilibrium.

Flow-induced scission of wormlike micelles in nonionic surfactant solutions under shear flow.

We investigate flow-induced scission of wormlike micelles with dissipative particle dynamics simulations of nonionic surfactant solutions under shear flow. To understand flow-induced scission in terms of micellar timescales, we propose a method to evaluate the longest relaxation time of unentangled surfactant micelles from the rotational relaxation time and the average lifetime at equilibrium. The mean squared displacement of surfactant molecules provides evidence that the longest relaxation time estimated by the proposed method serves as the characteristic timescale at equilibrium. We also demonstrate that the longest relaxation time plays an essential role in flow-induced scission. Using conditional statistics based on the aggregation number of micelles, we examine the statistical properties of the lifetime of wormlike micelles. We then conclude that flow-induced scission occurs when the Weissenberg number defined as the product of the longest relaxation time and the shear rate is larger than a threshold value.

Prognostic value of lymph node density for major salivary gland carcinoma without clinical lymph node metastasis.

BACKGROUND AND OBJECTIVE: This study aimed to investigate whether lymph node density (LND) was correlated with overall survival (OS) in major salivary gland carcinoma without clinical lymph node metastasis. METHODS: Sixty patients who were diagnosed with major salivary gland carcinoma without clinical lymph node metastasis were enrolled. Of these, 50 patients underwent neck dissection. LND was defined as the ratio of the number of positive lymph nodes to the total number of resected lymph nodes. RESULTS: An LND of ≥0.1 was significantly associated with a short OS (p < 0.05). Multivariate analysis with adjustment for pathological N classification and positive surgical margin showed that an LND of ≥0.1 is a predictor of OS. CONCLUSION: Results demonstrated that lymph node density functions as a predictor of outcomes for major salivary gland carcinoma without clinical lymph node metastasis.

Gross tumor volume in sinonasal tract cancer as a predictor of local recurrence after chemoradiotherapy.

OBJECTIVE: This study investigated whether gross tumor volume of the primary tumor before treatment was a predictor for local recurrence in patients with resectable sinonasal tract squamous cell carcinoma who were treated by chemoradiotherapy. METHODS: A total of 24 patients were enrolled. Pretreatment gross tumor volume of primary tumor was assessed by palpitation, perception and imaging. The cut-off value of the gross tumor volume for local recurrence was determined by receiver-operating curve analysis. A log-rank test and Cox's proportional hazards model were used for univariate and multivariate analyses with adjustment for the clinical T category (cT1-T4a/cT4b), respectively. RESULTS: In the univariate analysis, patients with the gross tumor volume ≥83.7 ml were significantly associated with shorter local recurrence-free rate (P = 0.0023) and disease-free survival (P = 0.0064) than those with gross tumor volume <83.7 ml. In the multivariate analysis, gross tumor volume ≥83.7 ml were significantly associated with shorter local recurrence-free rate (P = 0.041). CONCLUSIONS: Pretreatment gross tumor volume of primary tumor ≥83.7 ml was significantly associated with local recurrence-free rate in resectable sinonasal tract squamous cell carcinoma.

The Impact of Skeletal Muscle Depletion on Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Skeletal muscle depletion and sarcopenia have been reported as poor prognostic factors for several types of cancer. The aim of this study was to investigate the prognostic impact of skeletal muscle depletion and sarcopenia on the outcomes in head and neck cancer patients. METHODS: Patients with head and neck squamous cell carcinoma (HNSCC) treated from January 2013 to June 2014 were included in this study. The pretreatment cross-sectional area of skeletal muscle at the third lumbar vertebra (L3) was measured by computed tomography image analysis using the ImageJ software. L3 skeletal muscle index (SMI) and fat-free mass (FFM) were calculated. RESULTS: Eighty-five patients with HNSCC were included. The cut-off value of sarcopenia was set at SMI <46.7 cm2/m2 (males) and 30.3 cm2/m2 (females). The cut-off value of FFM was set at 42.3 kg (males) and 30.6 kg (females). Patients with a low SMI (sarcopenia) and low FFM had a significantly poorer prognosis than others, especially those who received definitive radiotherapy. Sarcopenia and low FFM are independent factors for poor prognosis in patients with HNSCC. CONCLUSION: The skeletal muscle area at L3 should be calculated when considering treatment options for head and neck cancer.

Comparisons of the clinical outcomes of different postoperative radiation strategies for treatment of head and neck squamous cell carcinoma.

PURPOSE: We previously reported unfavorable locoregional control with limited field postoperative radiotherapy for head and neck squamous cell carcinoma patients and thus revised the strategy to cover the whole neck. Head and neck squamous cell carcinoma Patients' outcomes were retrospectively analyzed to compare the efficacy of two treatments. MATERIAL AND METHODS: Before 2010, the clinical target volume covered the tumor bed and/or involved the neck region. Since 2011, whole-neck irradiation was planned. Univariate analysis, multivariate analysis, and propensity score matching were performed. The study included 275 patients: 186 received limited field postoperative radiotherapy and 89 received whole-neck postoperative radiotherapy. The median follow-up time for the entire cohort was 40.8 months. RESULTS: In univariate analysis, the radiation strategy had no significant effect on overall survival and progression-free survival. In multivariate analysis, whole-neck postoperative radiotherapy was a favorable factor for overall survival, progression-free survival, and locoregional control. Propensity score matching resulted in a cohort comprising 118 well-matched patients evenly divided between the limited field postoperative radiotherapy and whole-neck postoperative radiotherapy groups. Whole-neck postoperative radiotherapy group achieved a significantly better 2-year overall survival (56.4% vs. 78.1%; P = 0.003), 2-year progression-free survival (34.7% vs. 59.8%; P = 0.009), and 2-year locoregional control (54.4% vs. 83.2%; P < 0.001). The limited field postoperative radiotherapy group developed significantly more locoregional recurrences both in-field (35.2% vs. 15.1%, P = 0.003) and out-of-field (25.0% vs. 0%, P < 0.001) in the matched-pair cohort. CONCLUSION: Whole-neck postoperative radiotherapy is a more appropriate choice than limited field postoperative radiotherapy to improve overall survival, progression-free survival and locoregional control.

Comparison between chemoselection and definitive radiotherapy in patients with cervical esophageal squamous cell carcinoma.

BACKGROUD: Laryngeal preservation is an important consideration when treating cervical esophageal cancers (CECs) such as laryngeal cancer. The standard treatment for CEC allowing laryngeal preservation is chemoradiotherapy. However, in cases of laryngeal cancer, chemoselection has also been applied as a treatment strategy that promotes larynx preservation. This strategy involves assigning the appropriate radical treatment according to the primary tumor's response to induction chemotherapy. Since there have been no studies of the application of chemoselection in CEC cases, the present study compared the results, including laryngeal preservation rates, obtained upon applying chemoselection and chemoradiotherapy to CEC. STUDY DESIGN: This was a retrospective cohort study of cervical esophageal squamous cell carcinoma patients treated using chemoselection or chemoradiotherapy at Aichi Cancer Center Hospital between January 2000 and March 2013. A total of 42 patients were enrolled. RESULTS: The 2-year overall survival and laryngeal preservation rates for the chemoselection group versus the primary radiotherapy group were 65.1 and 57.3 versus 40 and 83.3%, respectively (P = 0.017 and P = 0.122, respectively). The 2-year locoregional control rates for the chemoselection and primary radiotherapy groups were 68 and 25%, respectively (P = 0.045). CONCLUSION: The chemoselection group achieved favorable results. Therefore, chemoselection can be applied as a treatment strategy for CEC.

The Charlson comorbidity index is a prognostic factor in sinonasal tract squamous cell carcinoma.

OBJECTIVE: High Charlson comorbidity index values have been reported to be associated with shorter overall survival in various types of cancer. We investigated whether Charlson comorbidity index values were correlated with overall survival in patients with resectable sinonasal tract squamous cell carcinoma. METHODS: Seventy-nine patients with resectable sinonasal tract squamous cell carcinoma were treated with curative intent. The Charlson comorbidity index values were calculated by the summation of the weight scores of 19 medical conditions (other than sinonasal tract squamous cell carcinoma) before treatment. The survival rate was analyzed according to the Kaplan-Meier method. Univariate and multivariate survival analyses were performed using the Wilcoxon test and the Cox proportional hazards model, respectively. RESULTS: According to a univariate analysis, a Charlson comorbidity index value ≥6 was found to be significantly correlated with shorter overall survival (P < 0.02). In the multivariate survival analysis with adjustment for the clinical T and N classification, age, sex, anatomical location, treatment group (radiotherapy/surgery) and chemotherapy (presence/absence), a Charlson comorbidity index value ≥6 was found to be associated with the significantly shorter overall survival. CONCLUSIONS: These results suggest that the Charlson comorbidity index functions as a prognostic factor in cases of resectable sinonasal tract squamous cell carcinoma.

Lymph node ratio predicts survival in hypopharyngeal cancer with positive lymph node metastasis.

The lymph node density (LND) has been reported to be a significant prognostic factor in various types of carcinoma. This study investigated whether the LND is associated with survival in patients with hypopharyngeal squamous cell carcinoma (HPSCC) who have positive lymph nodes without distant metastasis. Forty-six patients who were pathologically diagnosed with HPSCC with positive lymph nodes and without distant metastasis were enrolled in this study. The LND was defined as the ratio of positive lymph nodes to the total number of lymph nodes. An LND of ≥0.09 was found to be significantly correlated with a shorter overall (p = 0.044) and disease-specific (p = 0.019) survival according to a log-rank test. In a multivariate survival analysis using a Cox proportional hazards model adjusted for the pathological T category (pT3-4/pT1-2), pathological N category (pN2/pN1) and positive surgical margin and/or extracapsular spread (presence/absence), both an LND of ≥0.09 and pT3-4 category were associated with significantly shorter overall survival (p < 0.01) and disease-specific survival (p < 0.01). These results suggest that the LND functions as a prognostic factor for HPSCC patients with positive lymph nodes who do not have distant metastasis.

Combination therapy of oncolytic herpes simplex virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft.

Breast cancer is one of the most common and feared cancers faced by women. The prognosis of patients with advanced or recurrent breast cancer remains poor despite refinements in multimodality therapies involving chemotherapeutic and hormonal agents. Multimodal therapy with more specific and effective strategy is urgently needed. The oncolytic herpes simplex virus (HSV) has potential to become a new effective treatment option because of its broad host range and tumor selective viral distribution. Bevacizumab is a monoclonal antibody against VEGFA, which inhibits angiogenesis and therefore tumor growth. Our approach to enhance the antitumor effect of the oncolytic HSV is to combine oncolytic HSV HF10 and bevacizumab in the treatment of breast cancer. Our results showed that bevacizumab enhanced viral distribution as well as tumor hypoxia and expanded the population of apoptotic cells and therefore induced a synergistic antitumor effect. HF10 is expected to be a promising agent in combination with bevacizumab in the anticancer treatment.

Phase I Dose-escalation Clinical Trial of HF10 Oncolytic Herpes Virus in 17 Japanese Patients with Advanced Cancer.

Oncolytic virus therapy is a promising new therapeutic method, one of an eagerly anticipated class of biological therapies against cancer. There are many different classes of oncolytic virus. One of these, herpes oncolytic virus, is strongly oncolytic and has a large DNA genome as 150k bp. HF10 is a spontaneous mutant of herpes simplex virus -1 (HSV-1) that replicates within tumors and destroys cancers without damaging normal tissue and organs. Clinical trials of HF10 are underway in Japan and the United States. The first pilot study of HF10 was initiated in Japan in 2003. This study examined the safety and efficacy of HF10 in the treatment of breast cancer and head and neck cancers; the trial also included careful dose escalation studies. In 2005, a clinical trial using HF10 to treat pancreatic cancer was initiated. screened In this Japanese study, 17 patients received HF10 in their tumor sites. A clinical trial in the United States is also ongoing to evaluate safety, tolerability and evidence of antitumor activity in patients with refractory superficial solid tumors. Here, we report the evaluation of the 17 patients treated in Japan. Among the patients, 6 had recurrent breast cancer, 3 had recurrent head and neck cancer, and 8 had non-resectable pancreatic cancer. No severe adverse side effects have been observed, and some therapeutic potential has been reported based on pathological findings, tumor markers, and diagnostic radiography. Those results should encourage further clinical trials of HF10 around the world.

Predictive factors for dissection-free sentinel node micrometastases in early oral squamous cell carcinoma.

This sentinel node (SN) biopsy trial aimed to assess its effectiveness in identifying predictive factors of micrometastases and to determine whether elective neck dissection is necessary in oral squamous cell carcinoma. This retrospective study included 55 patients from three previous trials, with positive SNs. The relationship between the sizes of the metastatic focus and metastasis in non-sentinel node (NSN) was investigated. Four of the 55 largest metastatic focus were isolated tumor cells, and the remaining 51 were ranged from 0.2 to 15 mm, with a median of 2.6 mm. The difference of prevalence between 46 negative- and 9 positive-NSN was statistically significant with regard to age, long diameter of primary site and number of cases with regional recurrence. In comparing the size of largest metastatic focus dividing the number of positive SN, with metastaic focus range of < 3.0 mm in one-positive SN group, there were 18 (33%) negative-NSN and no positive-NSN. Regarding prognosis, 3-year overall survival rate of this group (n = 18) and other (n = 37) were 94% and 73% (p = 0.04), and 3-year recurrence free survival rate of this group and other were 94% and 51% (p = 0.03), respectively. Absolutely a further prospective clinical trial would be needed, micrometastases may be defined as solitary SN metastasis with < 3.0 mm of metastatic focus, and approximately 33% of neck dissections could be avoided using these criteria.

Predictive factors for false negatives following sentinel lymph node biopsy in early oral cavity cancer.

Prophylactic elective neck dissection (ND) with navigation surgery using radioisotope-based sentinel lymph node biopsy (SLNB) is non-inferior to elective ND in terms of survival but has an advantage in postoperative functional disability. We conducted a subgroup analysis to identify predictive factors for false-negative (FN)-SLNB in patients with early oral cavity cancer. This study is a supplementary analysis using the dataset of a previously reported randomized clinical trial on SLN navigation surgery for oral cancers. This study investigated the association of clinical and SLN-related factors with false-negative cases in the SLNB group. From 2011 to 2016, 275 patients were enrolled and randomly assigned to the ND and SLNB study groups, with 134 patients assigned to the SLNB group. In the SLNB group, seven cases with negative SLNs and neck recurrences were judged as FN-SLNBs according to the general definition. The number of detected SLNs with and without adjusting for the propensity score was significantly associated with FNs in the logistic analysis. FN-SLNB was associated with the number of identified SLNs, suggesting the need for careful postoperative monitoring for neck recurrence in patients with one or two identified SLNs after acquiring sufficient experience in the identification technique.

p16-positive oropharyngeal cancer with rare thyroid metastasis†: A case report.

Thyroid metastasis is rarely diagnosed, and the treatment outcomes in p16-positive oropharyngeal squamous cell carcinoma patients with rare thyroid metastasis have not been fully investigated. Here we describe the case of a patient with p16-positive oropharyngeal squamous cell carcinoma who was diagnosed with cT4 N2M1 with rare thyroid metastasis. The patient was a current smoker and was positive for human papillomavirus DNA, with disease progression at 49 days and death at 113 days after completion of cisplatin-based concurrent chemoradiotherapy. J. Med. Invest. 67 : 189-191, February, 2020.

Uptake of 18F-Fluorodeoxyglucose in Major Salivary Gland Cancer Predicts Survival Adjusting for Pathological Stage.

AIM: To investigate whether 18F-fluorodeoxyglucose uptake is associated with overall survival in patients with major salivary gland cancer using univariate and multivariate analyses after adjusting for pathological stage (eighth edition of the International Union Against Cancer). PATIENTS AND METHODS: A total of 32 patients with major salivary gland cancer treated with curative surgery were enrolled. Parameters for 18F-fluorodeoxyglucose uptake were assessed by positron-emission tomography combined with computed tomography. RESULTS: Using univariate and multivariate analyses after adjusting for pathological stage, a maximum standardized uptake value ≥26, peak standardized uptake value ≥20.3, metabolic tumor volume ≥9.7, and total lesion glycolysis ≥263 were significantly correlated with shorter overall survival. CONCLUSION: Parameters of 18F-fluorodeoxyglucose uptake in major salivary gland cancer are predictive of overall survival after adjusting for the pathological stage.

Epithelioid hemangioendothelioma of the parotid gland: a case report.

We present the case of a patient with epithelioid hemangioendothelioma of the parotid gland. A 70-year-old female developed swelling and pain in the lower part of the left ear 18 months previously and had visited a local hospital. Fine-needle aspiration cytology revealed no definitive diagnosis, but incisional biopsy under local anesthesia suggested epithelioid hemangioendothelioma. She was then transferred to our hospital, where she underwent total extirpation of the left parotid gland, left cervical lymph node dissection, and postoperative radiation therapy. However, she died from distant metastases 13 months after surgery. No previous study has reported any case of distant metastasis or death due to epithelioid hemangioendothelioma of the parotid gland. To the best of our knowledge, this is the first case report on distant metastasis and death due to the development of parotid gland cancer.

Treatment package time predicts cancer-specific survival and distant metastasis in laryngeal cancer.

We investigated whether treatment package time was significantly associated with survival outcomes of resectable locally-advanced laryngeal squamous cell carcinoma in patients who consecutively underwent various treatments, including surgery alone and salvage surgery for residual tumor. A total of 100 patients with clinical T3-T4 resectable laryngeal squamous cell carcinoma were enrolled in this study. The treatment package time was calculated in days between the start of any treatment and the end of all treatments, including postoperative radiotherapy and salvage surgery for residual tumors. Using a log-rank test, a treatment package time of ≥68 days showed significantly shorter cancer-specific (P=0.0013) and distant metastasis-free survival (P=0.0017), compared with a treatment package time of <68 days. Multivariate survival analyses of two Cox's hazards proportional models was conducted. In both model-1, which adjusted for cT3/cT4, cN0-1/cN2-3 and total laryngectomy/non-total laryngectomy, and model-2, which adjusted for cT3/cT4, cN0-1/cN2-3 and induction therapy/non-induction therapy, the cancer-specific survival and distant metastasis-free survival, according to treatment package time, were significantly longer with <68 days compared with ≥68 days (P<0.01). The present study demonstrated that a prolonged treatment package time is a prognostic factor for shorter cancer-specific and distant metastasis-free survival after various treatments for resectable locally-advanced laryngeal cancer.

Superficial Esophageal Cancer in a Fanconi Anemia Patient That Was Treated Successfully by Endoscopic Submucosal Resection.

Fanconi anemia (FA) is a disorder of chromosomal fragility characterized by progression to aplastic anemia, myelodysplastic syndrome, and leukemia. FA patients are also predisposed to solid cancers. A case of FA in an adult patient who developed tongue and superficial esophageal cancers following hematopoietic stem cell transplantation is reported. This case was considered significant because it is the first reported case of superficial esophageal cancer in an FA patient that was treated successfully by endoscopic submucosal resection.

Combination of Cetuximab and Oncolytic Virus Canerpaturev Synergistically Inhibits Human Colorectal Cancer Growth.

The naturally occurring oncolytic herpes simplex virus canerpaturev (C-REV), formerly HF10, proved its therapeutic efficacy and safety in multiple clinical trials against melanoma, pancreatic, breast, and head and neck cancers. Meanwhile, patients with colorectal cancer, which has increased in prevalence in recent decades, continue to have poor prognosis and morbidity. Combination therapy has better response rates than monotherapy. Hence, we investigated the antitumor efficacy of cetuximab, a widely used anti-epidermal growth factor receptor (EGFR) monoclonal antibody, and C-REV, either alone or in combination, in vitro and in an in vivo human colorectal xenograft model. In human colorectal cancer cell lines with different levels of EGFR expression (HT-29, WiDr, and CW2), C-REV exhibited cytotoxic effects in a time- and dose-dependent manner, irrespective of EGFR expression. Moreover, cetuximab had no effect on viral replication in vitro. Combining cetuximab and C-REV induced a synergistic antitumor effect in HT-29 tumor xenograft models by promoting the distribution of C-REV throughout the tumor and suppressing angiogenesis. Application of cetuximab prior to C-REV yielded better tumor regression than administration of the drug after the virus. Thus, cetuximab represents an ideal virus-associated agent for antitumor therapy, and combination therapy represents a promising antitumor strategy for human colorectal cancer.