Effect of tumor burden and growth rate on treatment outcomes of nivolumab in head and neck cancer.

BACKGROUND: Nivolumab improves overall survival (OS) in patients with platinum-refractory recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). In one study, however, Kaplan-Meier OS and progression-free survival (PFS) curves for the nivolumab and cytotoxic agent arms crossed at 3-6 months, suggesting that patients with initial resistance to immunotherapy might have better outcomes with cytotoxic treatment. Here, we explored the conditions and candidates which are predictive of nivolumab outcomes in R/M HNSCC. METHODS: We retrospectively reviewed the clinical records of 27 consecutive R/M HNSCC patients treated with nivolumab from 2014 to 2018. Tumor size was evaluated by RECIST ver.1.1. Tumor growth rate (Gr) was defined as 3log(D0/Dpre)/t, where D0 and Dpre are the sum of the diameters of the target lesions (SumTLs) at baseline and pre-baseline, and t is time, with 1t defined as 4 weeks. RESULTS: Twenty-five patients were enrolled. Survival was significantly worse in patients with disease progression within 3 months. Outcomes appeared poorer in patients with higher pre-treatment Gr and bigger SumTLs at baseline. We therefore explored the association between prognosis, Gr and SumTLs. Recursive partitioning analysis showed that the characteristics of patients with disease progression after 3 months were Gr < 0.76 and SumTLs < 31.0 mm. Further, Gr < 0.76 and SumTLs < 31.0 mm was associated with significantly longer PFS (p = 0.01) and OS (p < 0.01). CONCLUSIONS: These results suggest that Gr and SumTLs at baseline are significantly associated with OS and PFS in R/M HNSCC patients treated with nivolumab.

Comparison of mediastinal lymph node metastases from adenocarcinoma of the esophagogastric junction versus lower esophageal squamous cell carcinoma with involvement of the esophagogastric junction.

The distribution of mediastinal lymph node metastasis in patients with adenocarcinoma of the esophagogastric junction (AEG) remains unclear. Additionally, the distribution of nodal mediastinal metastasis from squamous cell carcinoma (SCC) of the lower esophagus with involvement of the esophagogastric junction remains unclear, given the very limited number of these patients. In this retrospective review, we compared the outcomes of radical lymphadenectomy of the mediastinum, including upper mediastinal lymphadenectomy, between patients with AEG and those with SCC. From 2005 to 2017, 69 consecutive patients underwent esophagectomy via right thoracotomy or minimally invasive esophagectomy for a Siewert type I or II tumor with esophageal invasion ≥3 cm. We analyzed the incidences of mediastinal lymph node metastasis in this group relative to those of 73 patients with SCC with involvement of the esophagogastric junction who consecutively underwent esophagectomy during the same period. Mediastinal lymph node metastasis was seen in 26 of 69 patients with AEG (38%), with upper, middle, lower mediastinal nodal metastasis instances of 20%, 17%, and 23%, respectively. Mediastinal lymph node metastasis was seen in 23 of 73 patients with SCC (32%), with upper, middle, lower mediastinal nodal metastasis instances of 12%, 16%, and 19%, respectively. This mediastinal lymph nodal metastasis distribution did not statistically differ between patients with AEG and those with SCC. The relapse-free survival outcomes were poor for patients with clinical (P < 0.01) or pathological (P < 0.01) nodal metastasis of the mediastinum with AEG. In contrast, patients with clinical or pathological mediastinal nodal metastases of SCC did not have extremely poor survival outcomes, compared to patients with AEG. Despite the limited dataset available for analysis, patients with AEG and those with SCC might exhibit similar incidences and distribution of mediastinal lymph node metastasis. However, the clinical or pathological metastasis of AEG to the mediastinum was associated with poor survival outcomes, even if radical mediastinal lymphadenectomy including the upper mediastinal lymphadenectomy was performed.

Oesophagectomy with or without supraclavicular lymphadenectomy after neoadjuvant treatment for squamous cell carcinoma of the oesophagus.

BACKGROUND: Treatment of supraclavicular nodes remains controversial among patients with oesophageal squamous cell carcinoma. This study assessed the outcomes of patients who underwent oesophagectomy with or without supraclavicular lymphadenectomy after neoadjuvant treatment. METHODS: This was a single-centre retrospective cohort study. Patients with oesophageal squamous cell carcinoma and clinically negative supraclavicular nodes who underwent oesophagectomy after neoadjuvant treatment between January 2005 and December 2015 were included. Overall and relapse-free survival were compared between patients who did or did not undergo supraclavicular nodal dissection. Propensity score matching was used to correct for differences in prognostic factors between the groups. RESULTS: Some 223 patients underwent supraclavicular lymphadenectomy. The prevalence of pathologically confirmed supraclavicular metastasis was 10·3 per cent, and these patients had poor 5-year relapse-free (7 per cent) and overall (14 per cent) survival. Only two of 55 patients who did not undergo supraclavicular lymphadenectomy had recurrent disease in the supraclavicular region without distant metastasis. There was no statistically significant difference between the groups in relapse-free survival (hazard ratio (HR) 0·95, 95 per cent c.i. 0·61 to 1·47; P = 0·821) or overall survival (HR 0·86, 0·52 to 1·40; P = 0·544). Similarly, no significant difference in relapse-free or overall survival was observed between the propensity score-matched groups. CONCLUSION: For patients with clinically negative supraclavicular lymph nodes, prophylactic supraclavicular lymphadenectomy may be omitted when neoadjuvant treatment is administered.

Clinical utility of exhaled carbon monoxide in assessing preoperative smoking status and risks of postoperative morbidity after esophagectomy.

Whereas smoking constitutes a significant risk factor for postesophagectomy morbidity, there is no reliable method to assess the smoking status of patients prior to the procedure. Since exhaled carbon monoxide (CO) is an indicator of recent smoking, this paper hypothesizes that this is a useful parameter in assessing current smoking status and may help predict morbidity following esophagectomy. Sixty-nine patients, who had undergone elective three-incision esophagectomy with two- or three-field lymphadenectomy for esophageal cancer, were prospectively studied between February 2015 and September 2017. At surgical admission, they were asked about their smoking history, their exhaled CO levels were evaluated, and they were grouped into three based on their CO levels. These were 0 parts per million (ppm), >0 and <7 ppm, and ≥7 ppm. Their postoperative morbidity was also assessed. Approximately 13.5% of the patients showed high levels of exhaled CO ≥ 7 ppm, despite preoperatively reporting smoking cessation for over a month. Morbidities of the Clavien-Dindo classification (CDc) ≥ II increased as exhaled CO levels increased and severe morbidity of CDc ≥ IIIb frequently was observed in patients with exhaled CO levels ≥7 ppm. The logistic regression analysis showed that exhaled CO level ≥7 ppm was an independent risk factor for severe postesophagectomy morbidity. Overall, the results of this study suggest that exhaled CO levels may be useful in estimating current smoking status and that it may also help give an estimation of the risk of postesophagectomy morbidity.

Failure of neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma.

Neoadjuvant treatment has become standard care for patients with resectable esophageal cancer. However, some patients cannot undergo surgery or curative resection because of disease progression during neoadjuvant treatment. The aim of this study is to identify the pretreatment characteristics of patients in whom neoadjuvant treatment failed. The study enrolled 231 patients who underwent chemotherapy with cisplatin and 5-fluorouracil (CF) as neoadjuvant therapy for T1N1-3 or T2-3 any-N esophageal squamous cell carcinoma (ESCC). Of these patients, 201 (87.0%) underwent curative resection (R0) and 30 (13.0%) could not undergo curative resection; 19 patients (8.2%) underwent incomplete resection (R1 or R2), and 11 patients (4.8%) could not undergo surgery because of disease progression. We compared clinical characteristics and survival between patients who underwent curative resection (curative group) and those who could not undergo curative resection (noncurative group) to determine the factors predicting noncurative treatment. The noncurative group had significantly worse disease-specific survival than the curative group (P < 0.001). All patients in the noncurative group had cT3 tumors. In 141 patients with cT3 tumors, those in the noncurative group were more likely to have higher serum SCC antigen concentration (P = 0.021), location of the main tumor in the upper to the middle third of the esophagus (P = 0.071), intramural metastases (P < 0.001), advanced N category (P = 0.016), and bulky lymph node metastases (P = 0.060). Multivariate logistic regression analysis identified location of the main tumor in the upper to the middle third of the esophagus (P = 0.047), intramural metastases (P = 0.002), and nodal metastases (N1, P = 0.014; N2, P = 0.015, respectively) as independent predictors of treatment failure in patients with cT3 tumors. Neoadjuvant CF therapy alone may not be effective for patients with cT3 tumors accompanied by these risk factors, and the efficacy of alternative strategies, such as triplet chemotherapy or chemoradiotherapy, should be evaluated.

Prognostic and clinical impact of sarcopenia in esophageal squamous cell carcinoma.

Recently, depletion of skeletal muscle mass (sarcopenia) has been linked to poor prognosis in several types of cancers, but has not been investigated in esophageal squamous cell carcinoma (ESCC). This retrospective study investigates the relationship between sarcopenia and clinical outcome in ESCC patients treated by surgical resection or definitive chemoradiation therapy (dCRT). The study was retrospectively conducted in a single academic hospital in Kumamoto, Japan, and involved 325 ESCC patients (256 surgical cases and 69 dCRT cases) treated between April 2005 and April 2011. Skeletal muscle mass was quantified by radiologic measures using standard computed tomography scans. The skeletal muscle tissue in the 325 ESCC patients was distributed as follows: mean: 47.10; median: 46.88; standard deviation (SD): 7.39; range: 31.48-71.11; interquartile range, 46.29-47.90. Skeletal muscle tissue was greater in male patients than in female patients (P < 0.0001), but was independent of other clinical and tumor features. Sarcopenia was not significantly associated with overall survival (log rank P = 0.54). Lymph node involvement significantly altered the relationship between sarcopenia and survival rate (P for interaction = 0.026). Sarcopenia significantly reduced the overall survival of patients without lymph node involvement (log rank P = 0.035), but was uncorrelated with overall survival in patients with lymph involvement (log rank, P = 0.31). The anastomosis leakage rate was significantly higher in the sarcopenia group than in the non-sarcopenia group (P = 0.032), but other surgical complications did not significantly differ between the two groups. Sarcopenia in ESCC patients without lymph node involvement is associated with poor prognosis, indicating sarcopenia as a potential biomarker for identifying patients likely to experience an inferior outcome. Moreover, sarcopenia was associated with anastomosis leakage but no other short-term surgical outcome.

Performance of a rapid human metapneumovirus antigen test during an outbreak in a long-term care facility.

Using a newly developed rapid test, an outbreak of human metapneumovirus (HMPV) infection in a long-term care facility was detected within only 2 days after the onset of symptoms in a putative index case. The outbreak was almost under control within 8 days mainly by zoning patients, with the exception of two cases of HMPV that were diagnosed 16 and 17 days after the onset of the outbreak. According to an immunological diagnosis as well as the rapid test, it was eventually proven that 18 patients had HMPV infections. We suspected that even asymptomatic residents, who had not been completely separated from the facility population, were a source of infection. That suggested that all asymptomatic residents should be tested and that the separation of the infected patients should be absolute, if an outbreak of HMPV infection is suspected in such a facility.

A phase II trial of paclitaxel plus biweekly cetuximab for patients with recurrent or metastatic head and neck cancer previously treated with both platinum-based chemotherapy and anti-PD-1 antibody.

BACKGROUND: An important unmet need for new treatment options remains for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) previously treated with both platinum-based chemotherapy and anti-programmed cell death protein 1 (PD-1) antibody. Retrospective studies suggest that previous treatment with immune checkpoint inhibitor might augment the efficacy of subsequent chemotherapy. Here, we conducted a phase II trial aimed to evaluate the efficacy and safety of paclitaxel plus biweekly cetuximab for patients in this setting. PATIENTS AND METHODS: This was a single-arm, multicenter, phase II trial. Key eligibility criteria were R/M-HNSCC, and previous treatment with both platinum-based chemotherapy and PD-1 antibody. Paclitaxel plus biweekly cetuximab consisted of weekly paclitaxel 100 mg/m2 (days 1, 8, 15) and biweekly cetuximab 500 mg/m2 (days 1, 15) with a cycle of 28 days until progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs) (Common Terminology Criteria for Adverse Events version 5.0). RESULTS: Between August 2020 and August 2022, 35 patients were enrolled, of whom 33 were assessable for response. ORR was 69.6% (95% confidence interval 51.2% to 84.4%). With a median follow-up period for survivors of 16.6 months, median PFS and OS were 5.5 and 13.3 months, respectively. DCR was 93.7%. Twenty-three patients (65%) experienced grade 3 or 4 AEs, including neutropenia (34%), infection (14%), leukopenia (11%), mucositis (8%), and pneumonitis (8%). Eight patients discontinued study treatment due to treatment-related AEs, and no treatment-related death was observed. CONCLUSIONS: Paclitaxel plus biweekly cetuximab showed highly encouraging efficacy and manageable toxicities in R/M-HNSCC patients previously treated with both platinum-based chemotherapy and PD-1 antibody. This combination therapy warrants further investigation in this setting.

Quantitative evaluation of oral function in acute and recovery phase of idiopathic facial palsy; a preliminary controlled study.

OBJECTIVES: Patients with peripheral facial palsy frequently complain of fluid leakage and food retention during meals. We investigated oral function during eating in adults with peripheral facial palsy. DESIGN: A prospective two-phase controlled observational study. SETTING: Data were collected at the ENT clinic in Nihon University Itabashi Hospital (patients) and Nihon University Dental Hospital (controls) between September 2009 and August 2011 and analysed at the Department of Oral Diagnostic Sciences in Nihon University School of Dentistry. PARTICIPANTS: Fourteen patients with acute idiopathic facial palsy and 14 controls completed Study 1. Sixteen patients with acute idiopathic facial palsy and 16 controls completed Study 2. MAIN OUTCOME MEASURES: In Study 1, oral vestibular cleansing capability was assessed by measuring the amount of rice remaining in the oral vestibule after mastication. In Study 2, masticatory efficiency was evaluated by measuring glucose eluted from gummy jelly during chewing. These oral functions were observed at the first visit and final visit (after patients with facial palsy had recovered). RESULTS: Oral vestibular cleansing capability at the first visit was significantly decreased by facial palsy (P < 0.001 versus healthy volunteers and P < 0.001 versus contralateral side) but recovered as facial muscular function improved (P = 0.034). There was a significant correlation between improvement in paralysis and decreased food retention (r = -0.528, P = 0.010). At the first visit, masticatory efficiency on the affected side was significantly lower than that of controls (P = 0.002) but had mostly recovered after resolution of facial palsy (P = 0.033). CONCLUSIONS: Oral functions were decreased by peripheral facial palsy. Oral vestibular cleansing capability was more significantly associated than masticatory efficiency with facial muscle function. Our data suggest that peripheral facial palsy impairs eating and worsens oral hygiene, which may result in oral disease.

Aberrant activation of the mTOR pathway and anti-tumour effect of everolimus on oesophageal squamous cell carcinoma.

BACKGROUND: The mammalian target of rapamycin (mTOR) protein is important for cellular growth and homeostasis. The presence and prognostic significance of inappropriate mTOR activation have been reported for several cancers. Mammalian target of rapamycin inhibitors, such as everolimus (RAD001), are in development and show promise as anti-cancer drugs; however, the therapeutic effect of everolimus on oesophageal squamous cell carcinoma (OSCC) remains unknown. METHODS: Phosphorylation of mTOR (p-mTOR) was evaluated in 167 resected OSCC tumours and 5 OSCC cell lines. The effects of everolimus on the OSCC cell lines TE4 and TE11 in vitro and alone or in combination with cisplatin on tumour growth in vivo were evaluated. RESULTS: Mammalian target of rapamycin phosphorylation was detected in 116 tumours (69.5%) and all the 5 OSCC cell lines. Everolimus suppressed p-mTOR downstream pathways, inhibited proliferation and invasion, and induced apoptosis in both TE4 and TE11 cells. In a mouse xenograft model established with TE4 and TE11 cells, everolimus alone or in combination with cisplatin inhibited tumour growth. CONCLUSION: The mTOR pathway was aberrantly activated in most OSCC tumours. Everolimus had a therapeutic effect both as a single agent and in combination with cisplatin. Everolimus could be a useful anti-cancer drug for patients with OSCC.

Estimating production costs and retail prices in different poultry housing systems: conventional, enriched cage, aviary, and barn in Japan.

For many producers, introduction of improved animal welfare systems is a turning point in their future production strategies as it increases production costs. The increase in egg retail prices is of growing concern not only for producers, but also for retailers and consumers. However, no report has calculated the estimated production costs or retail prices associated with introducing practices that support improved animal welfare in poultry farms in Japan. Therefore, this study aimed to estimate the production costs and table egg prices of 6 types of laying hen systems: conventional cage (CC): 8- and 12-tiers (CC8, CC12), enriched cage (EC): 8- and 12-tiers (EC8, EC12), aviary (AV), and barn systems (BR). Production costs include land purchases, construction costs of facilities, equipment and machinery, quantity of feed provided, farming materials invested, and wages. As a result, farm gate prices were estimated as CC8 = 12.19, CC12 = 12.19, EC8 = 14.52, EC12 = 14.52, AV = 21.14, and BR = 28.74 [yen/egg], and the production cost, including building the new farm, increased by EC8 = 19.1%, EC12 = 19.1%, AV = 73.4%, and BR = 135.7%, respectively, referring to the value of CC. The results show that the prices increase in systems between CC and BN. The retail price or table egg price was estimated to be CC8 = 24.68, CC12 = 24.68, EC8 = 28.07, EC12 = 28.07, AV = 37.27, and BR = 48.53 [yen/egg]. The retail price of BR is approximately twice that of CC. In addition, assuming that all of Japan's eggs were produced in the BR system, the soaring cost of eggs would likely affect the prices of factory eggs, such as liquid eggs and other products, thus affecting the prices of various food products. Understanding the significant management costs that affect the retail price of eggs would facilitate improved policies and practical approaches to support poultry farms and sustainable farming activities while addressing public concerns.

New proposal to revise the classification for squamous cell carcinoma of the external auditory canal and middle ear.

BACKGROUND: The prognosis of patients with advanced squamous cell carcinoma of the external auditory canal and middle ear has been improved by advances in skull base surgery and multidrug chemoradiotherapy during the last two decades. METHODS: Ninety-five patients with squamous cell carcinoma of the external auditory canal and middle ear who were treated between 1998 and 2017 were enrolled. The number of patients with tumour stages T1, T2, T3 and T4 was 15, 22, 24 and 34, respectively. Oncological outcomes and prognostic factors were retrospectively investigated. RESULTS: Among patients with T4 disease, invasion of the brain (p = 0.024), carotid artery (p = 0.049) and/or jugular vein (p = 0.040) were significant predictors of poor prognosis. The five-year overall survival rate of patients with at least one of these factors (T4b) was significantly lower than that of patients without these factors (T4a) (25.5 vs 65.5 per cent, p = 0.049). CONCLUSION: It is proposed that stage T4 be subclassified into T4a and T4b according to the prognostic factors.

Comparison of the in vitro activity of terbinafine and lanoconazole against dermatophytes.

The objective of this study was to compare the antifungal activity of terbinafine (TERB) with that of lanoconazole (LAN). Test isolates, which were clinical isolates of Japanese origin, included 10 strains each of Trichophyton rubrum, T. mentagrophytes and Epidermophyton floccosum. The minimum inhibitory concentration (MIC) of TERB and LAN against each dermatophyte isolate was determined according to the Clinical and Laboratory Standards Institute microbroth methodology, M38-A2. Minimum fungicidal concentrations were determined by subculturing the contents of each visibly clear well from the MIC assay for colony count. All LAN MICs were

Functional domains of alpha-catenin required for the strong state of cadherin-based cell adhesion.

The interaction of cadherin-catenin complex with the actin-based cytoskeleton through alpha-catenin is indispensable for cadherin-based cell adhesion activity. We reported previously that E-cadherin-alpha-catenin fusion molecules showed cell adhesion and cytoskeleton binding activities when expressed in nonepithelial L cells. Here, we constructed deletion mutants of E-cadherin-alpha-catenin fusion molecules lacking various domains of alpha-catenin and introduced them into L cells. Detailed analysis identified three distinct functional domains of alpha-catenin: a vinculin/alpha-actinin-binding domain, a ZO-1-binding domain, and an adhesion-modulation domain. Furthermore, cell dissociation assay revealed that the fusion molecules containing the ZO-1-binding domain in addition to the adhesion-modulation domain conferred the strong state of cell adhesion activity on transfectants, although those lacking the ZO-1-binding domain conferred only the weak state. The disorganization of actin-based cytoskeleton by cytochalasin D treatment shifted the cadherin-based cell adhesion from the strong to the weak state. In the epithelial cells, where alpha-catenin was not precisely colocalized with ZO-1, the ZO-1-binding domain did not completely support the strong state of cell adhesion activity. Our studies showed that the interaction of alpha-catenin with the actin-based cytoskeleton through the ZO-1-binding domain is required for the strong state of E-cadherin-based cell adhesion activity.

alpha-Catenin-vinculin interaction functions to organize the apical junctional complex in epithelial cells.

alphaE-catenin, a cadherin-associated protein, is required for tight junction (TJ) organization, but its role is poorly understood. We transfected an alphaE-catenin-deficient colon carcinoma line with a series of alphaE-catenin mutant constructs. The results showed that the amino acid 326-509 domain of this catenin was required to organize TJs, and its COOH-terminal domain was not essential for this process. The 326-509 internal domain was found to bind vinculin. When an NH2-terminal alphaE-catenin fragment, which is by itself unable to organize the TJ, was fused with the vinculin tail, this chimeric molecule could induce TJ assembly in the alphaE-catenin-deficient cells. In vinculin-null F9 cells, their apical junctional organization was impaired, and this phenotype was rescued by reexpression of vinculin. These results indicate that the alphaE-catenin-vinculin interaction plays a role in the assembly of the apical junctional complex in epithelia.

The effects of cigarette exposure on rat salivary proteins and salivary glands.

OBJECTIVE: Passive smoking is the involuntary inhalation of cigarette smoke (CS) and has an adverse impact on oral health. We examined the effect of CS exposure on saliva and salivary glands (SGs). METHODS: Cigarette smoke-exposed rats were intermittently housed in an animal chamber with whole-body exposure to CS until killed. Whole saliva was collected before CS exposure (0 day), and 15 and 30 days after the start of CS exposure. Saliva secretion was stimulated by administration of isoproterenol and pilocarpine after anesthesia. SGs were collected on 31 days. RESULTS: The increase in body weight of the CS-exposed rats was less than that of the control rats. Salivary flow rates did not differ at 0, 15 or 30 days after the start of CS exposure. However, the amylase and peroxidase activities and total protein content in the saliva were significantly lower in 15-day CS-exposed rats than in 15-day control rats. Histological examination of the SGs of CS-exposed rats showed vacuolar degeneration, vasodilation and hyperemia. CONCLUSION: These results suggest that CS exposure has adverse impacts on salivary composition and SGs, which could aggravate the oral environment.

Macrolide antibiotics like azithromycin increase lipopolysaccharide-induced IL-8 production by human gingival fibroblasts.

OBJECTIVE: Macrolide antibiotics are reported to modulate the production of cytokines in various type of cells. We examined the effect of macrolide antibiotics on inflammatory cytokines (IL-6 and IL-8) and chemical mediator (PGE(2)) and also matrix metalloproteinases (MMPs) productions by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS). METHODS: The effect of macrolide antibiotics [erythromycin (EM), azithromycin (AZM) and josamycin (JOM)] on HGFs proliferation were examined by MTT assay. HGFs were treated with LPS from Porphyromonas gingivalis (PgLPS) and macrolide antibiotics, and IL-6, IL-8 and PGE(2) levels were evaluated by ELISA. MMPs were detected by gelatin zymography. RESULTS: AZM slightly but significantly decreased HGFs proliferation, while EM and JOM did not affected. AZM increased PgLPS-induced IL-8 production dose-dependently, while AZM did not alter IL-6 and PGE2 productions. EM and JOM did not altered PgLPS-induced IL-6, IL-8 and PGE(2) productions. All macrolide antibiotics did not alter MMPs production. These results indicate that macrolide antibiotics have no direct anti-inflammatory effect. However, the use of the inhibitors of cell signaling pathway failed to reveal the mechanism that AZM enhanced PgLPS-induced IL-8 production. CONCLUSION: These results suggest macrolide antibiotics have an indirect anti-inflammatory effect as a result of their antimicrobial properties. Because AZM increased LPS-induced IL-8 production by HGFs, the possibility is considered that neutrophils may be migrated to periodontal tissue and phagocytize the periodontopathic bacteria more efficiently.

Predicting the therapeutic effect of carbamazepine in trigeminal neuralgia by analysis of neurovascular compression utilizing magnetic resonance cisternography.

The aim of this study was to determine whether the evaluation of neurovascular compression (NVC) using new criteria on magnetic resonance (MR) cisternography improves the prediction of the curative effects of carbamazepine (CBZ) in trigeminal neuralgia (TN). In this study, a new analysis of NVC using MR cisternography was performed retrospectively for 280 patients with clinical signs and symptoms suggesting TN. The new analysis examined whether the site of the NVC was less than 3mm from the edge of the exit point and within the first third of the root entry zone on MR cisternography. Prediction of the curative effects of CBZ using the new evaluation of distance to the NVC improved on the predictive ability of the previous method of calculating the NVC volume (Mantel-Haenszel coefficient, P<0.01). In particular, initial treatment with CBZ 100mg/day for 2 weeks appeared more effective for patients with NVC volumes of ≤5mm3 plus a distance to the NVC of ≤3mm, than for those with NVC volumes >5mm3. The evaluation of NVC on MR cisternography using this new approach appears to be more useful than the previous method for predicting the initial treatment response in patients with TN.

A 12-year Recurrence-free Survival After Multidisciplinary Treatment for a Patient With Combined Hepatocellular-Cholangiocarcinoma.

We report a 64-year-old woman with a 9-cm liver tumor in the left lateral section. The patient had neither hepatitis B or C virus infection, nor cirrhosis. Carbohydrate antigen 19-9 (CA 19-9) level was 1,889 U/ml. We also suspected bulky hilar lymph node metastasis, and a left lateral sectionectomy without lymph node dissection (R2) was performed. The pathological findings led to diagnosis of combined hepatocellular and cholangiocarcinoma. Three weeks post-operation, the patient underwent hepatic arterial infusion chemotherapy with cisplatin, fluorouracil, and mitomycin C. In addition, a total dose of 45 Gy of irradiation for the hilar lymph node was performed; while oral tegafur-uracil (UFT) has been administered for 10 years at a dose of 400 mg/day. The CA19-9 level of the patient was normalized after hepatectomy, hepatic arterial infusion, irradiation for hilar lymph node, and oral UFT administration. Currently, the patient is alive without any relapse for 12 years post-operation.