Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05).

BACKGROUND: In Japan, S-1 plus cisplatin has been used as first-line therapy for advanced gastric cancer (AGC). Patients with no response to first-line treatment with S-1 often receive a taxane-alone or irinotecan-alone as second-line treatment. However, second-line treatment with S-1 plus irinotecan is widely used in patients with AGC resistant to first-line S-1-based chemotherapy. The goal of this trial was to determine whether the consecutive use of S-1 plus irinotecan improves survival when compared with irinotecan-alone as second-line treatment for AGC. PATIENTS AND METHODS: Patients who had disease progression during first-line S-1-based chemotherapy were randomly assigned to receive S-1 plus irinotecan or irinotecan-alone. The S-1 plus irinotecan group received oral S-1 (40-60 mg/m(2)) on days 1-14 and intravenous irinotecan (150 mg/m(2)) on day 1 of a 21-day cycle. The irinotecan-alone group received the same dose of irinotecan intravenously on day 1 of a 14-day cycle. The primary end point was overall survival (OS). RESULTS: From February 2008 to May 2011, a total of 304 patients were enrolled. The median OS was 8.8 months in the S-1 plus irinotecan group and 9.5 months in the irinotecan-alone group. This difference was not significant (hazard ratio for death, 0.99; 95% confidence interval 0.78-1.25; P = 0.92). Grade 3 or higher toxicities were more common in the S-1 plus irinotecan group than in the irinotecan-alone group. CONCLUSION: The consecutive use of S-1 plus irinotecan is not recommended as second-line treatment in patients who are refractory to S-1-based first-line chemotherapy. ClinicalTrials.gov ID: NCT00639327.

Phase III placebo-controlled double-blind randomized trial of radiotherapy for stage IIB-IVA cervical cancer with or without immunomodulator Z-100: a JGOG study.

BACKGROUND: Based on the result of our previous study showing better overall survival (OS) at the lower dose (0.2 µg) of immunomodulator Z-100 than higher dose (40 µg) in patients with locally advanced cervical cancer who received radiotherapy, we conducted a placebo-controlled double-blind randomized trial. PATIENTS AND METHODS: Patients of stages IIB-IVA squamous cell carcinoma of the uterine cervix were randomly assigned to receive Z-100 at 0.2 µg (Z) or placebo (P). The study agent was given subcutaneously twice a week during the radiotherapy, followed by maintenance therapy by administering once every 2 weeks until disease progression. Primary end point was OS, and secondary end points were recurrence-free survival, and toxicity. RESULTS: A total of 249 patients were randomized. Death events occurred extremely slower than expected, and Independent Data Monitoring Committee recommended to analyze the survival result prematurely. The 5-year OS rate was 75.7% [95% confidence interval (CI) 66.4% to 82.8%] for Arm Z and 65.8% (95% CI 56.2% to 73.8%) for Arm P (P = 0.07); hazard ratio was 0.65 (95% CI 0.40-1.04). Survival benefit in Arm Z was observed regardless of chemoradiation or radiation alone. There was no trend in recurrence-free survival between the two arms. Side-effects were not different between two arms. CONCLUSION: Z-100 showed a trend of improvement on OS in locally advanced cervical cancer, although the statistical power was less than anticipated because survival rates were unexpectedly higher than expected for both arms. Validation of potential survival benefit of immune modulation should be made. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: C000000221.

Phase II multi-institutional prospective randomised trial comparing S-1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent advanced gastric cancer.

BACKGROUND: A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting. METHODS: Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m(-2) twice daily) on days 1-14 plus paclitaxel (60 mg m(-2)) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m(-2) twice daily) on days 1-21 plus cisplatin (60 mg m(-2)) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7%; P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin. CONCLUSION: S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials.

Association between Inflammation and Functional Outcome in Patients with Sarcopenic Dysphagia.

OBJECTIVES: This study aimed to investigate whether inflammation affects the outcome of swallowing ability to improve treatment for sarcopenic dysphagia. DESIGN: A retrospective observational cohort study was performed using data from the Japanese sarcopenic dysphagia database. SETTING: The database was constructed using data from 19 hospitals and one home visiting rehabilitation team. PARTICIPANTS: Patients with sarcopenic dysphagia with measurements of C-reactive protein (CRP) and serum albumin (Alb) were included. MEASUREMENTS: Patients were assigned to two groups using CRP, Alb, and the Japanese modified Glasgow Prognostic Score (mGPS). The Food Intake LEVEL Scale (FILS) was measured at the times of admission and follow-up (FILS follow-up) to assess swallowing function. RESULTS: A total of 197 patients were included. Mean or median values of each parameter were as follows: age: 83.8±8.7, Alb: 3.2 ± 0.6 g/dL, CRP: 8.0 [3.0, 29.0] mg/L, mGPS: 1 [1-2], FILS: 7 [6-8], FILS follow-up: 8 [7-8], and duration of follow-up: 57.0 [27.0, 85.0] days. The FILS score at follow-up was significantly lower in the high CRP group (≥ 5.0 mg/L) than in the low CRP group (< 5.0 mg/L) (p = 0.01). Further, the FILS score at follow-up was significantly lower in the high mGPS group (class; 2) than in the low mGPS group (class; 0 and 1) (p = 0.03). In the multiple linear regression analyses without FILS at baseline, CRP and mGPS were independent risk factors for FILS follow-up. When FILS at baseline was entered, CRP and mGPS were not an independent risk factors for FILS follow-up. CONCLUSIONS: Inflammation could modify the outcome of the patients with sarcopenic dysphagia. Inflammation may be an important risk factor in evaluating patients with sarcopenic dysphagia.

Prevalence of Hoarseness and Its Association with Severity of Dysphagia in Patients with Sarcopenic Dysphagia.

OBJECTIVES: To investigate the prevalence of hoarseness and its association with the severity of dysphagia in patients with sarcopenic dysphagia. DESIGN: Cross-sectional study using the Japanese sarcopenic dysphagia database. SETTING: 19 hospitals including 9 acute care hospitals, 8 rehabilitation hospitals, 2 long-term care hospitals, and 1 home visit rehabilitation team. PARTICIPANTS: 287 patients with sarcopenic dysphagia, aged 20 years and older. MEASUREMENTS: Sarcopenic dysphagia was diagnosed using a reliable and validated diagnostic algorithm for the condition. The presence and characteristics of hoarseness classified as breathy, rough, asthenic, and strained were assessed. The prevalence of hoarseness and the relationship between hoarseness and Food Intake LEVEL Scale (FILS) were examined. Order logistic regression analysis adjusted for age, sex, naso-gastric tube, and handgrip strength was used to examine the relationship between hoarseness and FILS at baseline and at follow-up. RESULTS: The mean age was 83 ± 10 years. Seventy-four (26%) patients had hoarseness, while 32 (11%), 20 (7%), 22 (8%), and 0 (0%) patients had breathy, rough, asthenic, and strained hoarseness, respectively. Median FILS at the initial evaluation was 7 (interquartile range, 5-8). Hoarseness (ß=0.747, 95% confidence intervals= 0.229, 1.265, p=0.005), age, sex, naso-gastric tube, and handgrip strength were associated independently with baseline FILS, while hoarseness (ß=0.213, 95% confidence intervals= -0.324, 0.750, p=0.438) was not associated independently with the FILS at follow-up. CONCLUSIONS: Hoarseness was associated with the severity of dysphagia at baseline, however not a prognostic factor for sarcopenic dysphagia. Resistance training of swallowing and respiratory muscles and voice training as part of rehabilitation nutrition might be useful for treating sarcopenic dysphagia.

Induction of human autologous cytotoxic T lymphocytes on formalin-fixed and paraffin-embedded tumour sections.

Human autologous tumour-specific cytotoxic T lymphocytes (CTL) were generated from peripheral blood on small formalin-fixed paraffin-embedded sections of a gastric cancer. The CTL killed live target cells at an effector/target ratio of 1 within 24 hours and showed the same target specificity as those induced on live cancer cells. The killing activity of the CTL lasted for more than four months in culture and was inhibited by antibodies against CD8 and MHC-class I. These results suggest that adoptive immunotherapy of tumours will be possible with CTL induced on a stable source of tumour antigen.

The p21 cyclin-dependent kinase inhibitor suppresses tumorigenicity in vivo.

The p21 gene encodes a cyclin-dependent kinase inhibitor that affects cell-cycle progression, but the potential of this gene product to serve as a tumour suppressor in vivo has not been established. In this report, we show that the growth of malignant cells in vitro and in vivo is inhibited by expression of p21. Expression of p21 resulted in an accumulation of cells in G0/G1, altered morphology, and cell differentiation, but apoptosis was not induced. Introduction of p21 with adenoviral vectors into malignant cells completely suppressed their growth in vivo and also reduced the growth of established pre-existing tumours. Gene transfer of p21 may provide a molecular genetic approach to arresting cancer cell growth by committing malignant cells irreversibly to a pathway of terminal differentiation.

Sarcopenic Dysphagia with Low Tongue Pressure Is Associated with Worsening of Swallowing, Nutritional Status, and Activities of Daily Living.

OBJECTIVES: According to the recently proposed diagnostic criteria for sarcopenic dysphagia, sarcopenic dysphagia can be classified as probable or possible based on tongue pressure. However, it is unclear whether patients with probable and possible sarcopenic dysphagia have different characteristics. Therefore, this study aimed to investigate whether patients with possible and probable sarcopenic dysphagia have different clinical characteristics. DESIGN: A cross-sectional study. SETTING: A rehabilitation hospital. PARTICIPANTS: In total, 129 patients aged ≥65 years with sarcopenic dysphagia were included. METHODS: A tongue pressure of <20 kPa was indicative of probable sarcopenic dysphagia, and a tongue pressure of ≥20 kPa was indicative of possible sarcopenic dysphagia. Kuchi-Kara Taberu (KT) index scores were compared between the probable or possible sarcopenic dysphagia groups. RESULTS: According to the tongue pressure, 76 and 53 patients were classified into the probable and possible sarcopenic dysphagia groups, respectively. In multiple linear regression analysis, the presence of probable sarcopenic dysphagia was independently associated with the total KT index score (standardized coefficient: -0.313, regression coefficient: -4.500, 95% confidence interval [CI], -6.920 to -2.080, P < 0.001). The presence of probable sarcopenic dysphagia was independently associated with some subitems of the KT index (willingness to eat, cognitive function while eating, oral preparatory and propulsive phase, severity of pharyngeal dysphagia, eating behavior, and daily living activities). CONCLUSIONS: Patients with probable sarcopenic dysphagia were characterized by poor overall eating-related conditions, especially poor swallowing ability, ability to perform activities of daily living, and nutritional status.

Biochemical nature of an Fc mu receptor on human B-lineage cells.

An IgM-binding protein of approximately 60 kD has been identified on activated B cells, but not on resting and activated T cells, monocytes, or granulocytes. Here, we characterize this IgM-binding protein as a receptor for the Fc portion (CH3 and/or CH4 domains) of IgM molecules (Fc microR). The Fc microR can be expressed as a cell surface activation antigen throughout the pre-B and B cell stages in differentiation. Receptor expression is not directly linked with IgM production, as both mu- pre-B cells and isotype-switched B cells may express the Fc microR. The receptor molecules produced by both pre-B and B cells are identical in size and are characterized as an acidic sialoglycoprotein with O-linked, but no N-linked, oligosaccharide. The Fc microR is anchored to the surface of B-lineage cells via a glycosyl phosphatidylinositol linkage. The Fc microR is thus the third member of a family of Fc receptors expressed on B-lineage cells, and its preferential expression on activated B cells suggests a potential role in the response to antigens.

Moiré Potential, Lattice Corrugation, and Band Gap Spatial Variation in a Twist-Free MoTe2/MoS2 Heterobilayer.

To have a fully first-principles description of the moiré pattern in transition-metal dichalcogenide heterobilayers, we have carried out density functional theory calculations on a MoTe2(9 × 9)/MoS2(10 × 10) stacking, which has a superlattice larger than an exciton yet not large enough to justify a continuum model treatment. Lattice corrugation is found to be significant in both monolayers, yet its effect on the electronic properties is marginal. We reveal that the variation of the average local potential near Mo atoms in both MoTe2 and MoS2 layers displays a conspicuous moiré pattern. They are the intralayer moiré potentials correlating closely with the spatial variation of the valence band maximum and conduction band minimum. The interlayer moiré potential, defined as the difference between the two intralayer moiré potentials, changes roughly in proportion to the band gap variation in the moiré cell. This finding might be instructive in chemical engineering of van der Waals bilayers.

Tongue surface model can predict radiation tongue mucositis due to intensity-modulated radiation therapy for head and neck cancer.

Acute radiation tongue mucositis has a profound effect on talking and eating. We examined whether the dose-volume histogram obtained from the tongue surface model correlates with mucositis severity, and whether it is useful for predicting acute radiation tongue mucositis in patients with head and neck cancer treated with intensity-modulated radiation therapy. Thirty-six patients who received intensity-modulated radiation therapy for head and neck cancer were analysed for acute radiation tongue mucositis according to the Common Terminology Criteria for Adverse Events, version 4.0, as well as the Radiation Therapy Oncology Group scoring systems. The corresponding high-dose locations in anatomical sub-regions in the tongue surface model and the development of high-grade acute radiation tongue mucositis were compared. The mucositis sites coincided with the high-dose anatomical sub-regions in the tongue surface model. There was a clear dose-response relationship between the mean dose to the tongue and the acute radiation tongue mucositis Radiation Therapy Oncology Group grade. According to the dose-volume histogram, patients receiving 16.0-73.0 Gy to the tongue were susceptible to grade 2-3 toxicity. The tongue surface model can predict the site and severity of acute radiation tongue mucositis. In future, radiation treatment plans ccould be optimized using this model.

Prognostic significance of the expression of MUC1 and collagen type IV in advanced gastric carcinoma.

BACKGROUND: Scirrhous gastric carcinoma is characterized by excessive deposition of collagen in the stroma. However, the clinical significance of this fibrosis of the stomach has not been clarified. The aim of this study was to examine the fibrotic mechanism in several histological types of gastric carcinoma, and the combination of MUC1 and collagen type IV as a possible predictor of patient survival. METHODS: One hundred and two paraffin-embedded specimens of gastric carcinoma were examined by immunohistochemical staining using monoclonal antibodies against collagen type IV and MUC1. RESULTS: Collagen type IV-positive expression was significantly associated with depth of wall penetration (P = 0.025) and stage (P = 0.023). There was a significant relationship between MUC1-positive expression and interstitial collagen type IV-positive expression (P = 0.035). Survival was shorter for patients with the combination of MUC1-positive expression and interstitial collagen type IV-negative expression than for those with other expression patterns. CONCLUSION: In patients with differentiated-type advanced gastric carcinoma, the combination of MUC1-positive and interstitial collagen type IV-negative expression may be a marker of unfavourable prognosis.

Identification of independent APP locus duplication in Japanese patients with early-onset Alzheimer disease.

BACKGROUND: The occurrence of duplications of the amyloid precursor protein gene (APP) has been described in European families with early-onset familial Alzheimer disease (EO-FAD) and cerebral amyloid angiopathy. However, the contribution of APP duplication to the development of AD in other ethnic populations remains undetermined. METHODS: The occurrence of APP duplication in probands from 25 families with FAD and 11 sporadic EO-AD cases in the Japanese population was examined by quantitative PCR and microarray-based comparative genomic hybridisation analyses. APP expression level was determined by real-time quantitative reverse-transcription (RT) PCR analysis using mRNA extracted from the peripheral blood of the patients. RESULTS: We identified APP locus duplications in two unrelated EO-FAD families. The duplicated genomic regions in two patients of these families differed from each other. No APP duplication was found in the late-onset FAD families or sporadic EO-AD patients. The patients with APP duplication developed insidious memory disturbance in their fifties without intracerebral haemorrhage and epilepsy. Quantitative RT-PCR analysis showed the increased APP mRNA expression levels in these patients compared with those in age- and sex-matched controls. CONCLUSIONS: Our results suggest that APP duplication should be considered in patients with EO-FAD in various ethnic groups, and that increased APP mRNA expression level owing to APP duplication contributes to AD development.

Gene therapy for vascular smooth muscle cell proliferation after arterial injury.

Accumulation of vascular smooth muscle cells as a consequence of arterial injury is a major feature of vascular proliferative disorders. Molecular approaches to the inhibition of smooth muscle cell proliferation in these settings could potentially limit intimal expansion. This problem was approached by introducing adenoviral vectors encoding the herpesvirus thymidine kinase (tk) into porcine arteries that had been injured by a balloon on a catheter. These smooth muscle cells were shown to be infectable with adenoviral vectors, and introduction of the tk gene rendered them sensitive to the nucleoside analog ganciclovir. When this vector was introduced into porcine arteries immediately after a balloon injury, intimal hyperplasia decreased after a course of ganciclovir treatment. No major local or systemic toxicities were observed. These data suggest that transient expression of an enzyme that catalyzes the formation of a cytotoxic drug locally may limit smooth muscle cell proliferation in response to balloon injury.

Formation of fullerides and fullerene-based heterostructures.

Two potassium fulleride phases, metallic K(3)C(60) and nonmetallic K(6)C(60), are formed when potassium is incorporated into thin C(60) films under ultrahigh vacuum conditions. Phase separation is observed for intermediate stoichiometries. Results obtained for the C(60)-K(3)C(60) heterostructure demonstrate that it is stable against potassium migration from the K(3)C(60) phase. In contrast, the C(60)-K(6)C(60) interface is not stable and K(3)C(60) is formed.

Uranium stabilization of c28: a tetravalent fullerene.

Laser vaporization experiments with graphite in a supersonic cluster beam apparatus indicate that the smallest fullerene to form in substantial abundance is C(28). Although ab initio quantum chemical calculations predict that this cluster will favor a tetrahedral cage structure, it is electronically open shell. Further calculations reveal that C(28) in this structure should behave as a sort of hollow superatom with an effective valence of 4. This tetravalence should be exhibited toward chemical bonding both on the outside and on the inside of the cage. Thus, stable closed-shell derivatives of C(28) with large highest occupied molecular orbital-lowest unoccupied molecular orbital gaps should be attainable either by reacting at the four tetrahedral vertices on the outside of the C(28) cage to make, for example, C(28)H(4), or by trapping a tetravalent atom inside the cage to make endothedral fullerenes such as Ti@C(28). An example of this second, inside route to C(28) stabilization is reported here: the laser and carbon-arc production of U@C(28).

[Surgical treatment for infective endocarditis].

OBJECTIVE: Surgery for infective endocarditis (IE) is technically demanding, especially the one for active IE. METHODS: Operations were performed in 21 patients with a mean age of 52.2 +/- 18.8 years. Fifteen patients were male, and 6 were female. There were 15 patients with active IE and 6 patients with healed IE. Isolated pathogens were Streptococcus in 8 cases, Staphylococcus in 3, and Enterococcus in 2. Two patients had prosthetic valve endocarditis. When the lesions affected the aortic valve, aortic valve replacement (AVR) was performed. When the lesions affected the mitral or tricuspid valves, valve repair was the treatment of choice. RESULTS: Six patients underwent AVR and 15 patients underwent a mitral valve operation (mitral valve repair in 13, replacement in 2). In 2 patients, mitral valve repair was changed to replacement, judged by intraoperative transesophageal echocardiogram. One patient underwent isolated tricuspid valve repair. Total survival and survival free of reoperation at 45 months was 95.2%. The grade of mitral regurgitation (MR) decreased from 3.7 +/- 0.1 to 0.2 +/- 0.1, and that of tricuspid valve regurgitation (TR) recovered from 3.5 +/- 0.5 to 1.0 +/- 1.0 at 21 +/- 15 months after the operation. CONCLUSIONS: Valve repair operations were useful in the mitral and tricuspid valve positions, even in the presence of active IE. Both mechanical valve and bioprosthesis showed good results after AVR for IE.

A step towards international prospective trials in carbon ion radiotherapy: investigation of factors influencing dose distribution in the facilities in operation based on a case of skull base chordoma.

BACKGROUND: Carbon ion radiotherapy (CIRT) has been delivered to more than 20,000 patients worldwide. International trials have been recommended in order to emphasize the actual benefits. The ULICE program (Union of Light Ion Centers in Europe) addressed the need for harmonization of CIRT practices. A comparative knowledge of the sources and magnitudes of uncertainties altering dose distribution and clinical effects during the whole CIRT procedure is required in that aim. METHODS: As part of ULICE WP2 task group, we sent a centrally reviewed questionnaire exploring candidate sources of uncertainties in dose deposition to the ten CIRT facilities in operation by February 2017. We aimed to explore native beam characterization, immobilization, anatomic data acquisition, target volumes and organs at risks delineation, treatment planning, dose delivery, quality assurance prior and during treatment. The responders had to consider the clinical case of a clival chordoma eligible for postoperative CIRT according to their clinical practice. With the results, our task group discussed ways to harmonize CIRT practices. RESULTS: We received 5 surveys from facilities that have treated 77% of the patients worldwide per November 2017. We pointed out the singularity of the facilities and beam delivery systems, a divergent definition of target volumes, the multiplicity of TPS and equieffective dose calculation approximations. CONCLUSION: Multiple uncertainties affect equieffective dose definition, deposition and calculation in CIRT. Although it is not possible to harmonize all the steps of the CIRT planning between the centers, our working group proposed counter-measures addressing the improvable limitations.

Characterization of adipose tissue-derived cells isolated with the Celution system.

BACKGROUND: The therapeutic potential of using stem cells is tremendous. Mesenchymal stromal cells (MSC) have now been isolated in various tissues including bone marrow (BM), muscle, skin and adipose tissue. Among them, adipose tissue could be one of the most suitable cell sources for cell therapy, because of its easy accessibility, minimal morbidity and abundance of stem cells. The large numbers of stem cells in adipose tissue means that clinically relevant stem cell numbers could be extracted from the tissue, potentially eliminating the need for in vitro expansion. To utilize these characteristics of adipose tissue fully, Cytori Therapeutics Inc. has developed a closed system called Celution to isolate and concentrate stem cells and regenerative cells automatically from adipose tissue. METHODS: Adipose tissue-derived cells were isolated using the Celution system. The output from the Celution was characterized using multicolor FACS analysis with CD31, CD34, CD45, CD90, CD105 and CD146. The multidifferentiation potential of the cells was analyzed using adipogenic and osteogenic media. RESULTS: Our results showed that cells from the Celution are composed of heterogeneous cell populations including adipose-derived stem cells (ASC) (CD31- CD34+ CD45- CD90+ CD105- CD146-), endothelial (progenitor) cells (CD31+ CD34+ CD45- CD90+ CD105- CD146+) and vascular smooth muscle cells (CD31- CD34+ CD45- CD90+ CD105- CD146+). We also confirmed the output contains cells able to differentiate into adipogenic and osteogenic phenotypes. Our results show that cells isolated with the Celution and manually are equivalent. DISCUSSION: Cells from adipose tissue can be processed by Celution within the time frame of a single surgical procedure. This system could provide a 'real-time' treatment setting that is cost-effective and safe.

Fluorine diffusion assisted by diffusing silicon on the Si(111)-(7x7) surface.

The diffusion process of fluorine (F) atoms on the Si(111)-(7x7) surface is investigated using high-temperature scanning tunneling microscopy. The kinetic parameters of F hopping agree well with those of the diffusing silicon (Si) atoms, which implies that of all reaction processes, the Si diffusion serves as the rate-determining one. Deposition of Si on the surface is found to enhance F hopping, which supports the above-mentioned observation. Theory reveals that the replacement of F adsorption sites by diffusing Si atoms is the key process in the diffusion mechanism.