Masaya Uesato

Pre-operative dental brushing can reduce the risk of postoperative pneumonia in esophageal cancer patients

BACKGROUND The presence of pathogens in dental plaque is a risk factor associated with postoperative pneumonia in esophageal cancer patients. The effectiveness of pre-operative dental brushing to decrease the risk of postoperative pneumonia in esophageal cancer patients was evaluated prospectively. METHODS A total of 86 thoracic esophageal cancer patients who underwent an esophagectomy were investigated. Patients were divided into 2 groups: the control group (41 patients) and the pre-operative dental brushing group (45 patients). The patients in the brushing group were assigned to brush their teeth 5 times a day. After the operation, the frequency of postoperative pneumonia and need for tracheostomy for pulmonary treatment was calculated. RESULTS Postoperative pneumonia was decreased markedly from 32% to 9% (P = .013), and the frequency of postoperative pneumonia requiring tracheostomy decreased from 12% to 0% in the dental brushing group, respectively. Limiting the patients who had positive pathogenic bacteria in their dental plaque on their admission, the frequency of postoperative pneumonia was decreased from 71% (5 of 7 patients) in the control group to 17% (2 of 12 patients) in the dental brushing group (P = .045). CONCLUSION Frequent pre-operative dental brushing is performed easily and seems to prevent postoperative pneumonia in esophageal cancer patients.

The overall prevalence of metastasis in T1 esophageal squamous cell carcinoma: a retrospective analysis of 295 patients.

Objectives:T1 esophageal squamous cell carcinoma (ESCC) has a low, but still present, risk of lymph node (LN) metastasis. Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is often applied for T1 ESCC. To achieve successful treatment by EMR/ESD, the risk of LN metastases, LN recurrence, and hematological recurrence need to be better understood. The aim of this study was to determine the precise risk for metastasis in T1 ESCC. Methods:We divided 295 patients with T1 ESCC who underwent surgery and/or ESD/EMR into 6 categories (m1, m2, m3, sm1, sm2, and sm3). Their risks of LN metastasis, LN recurrence, hematological recurrence, and the outcome were determined. Results:The rates of LN metastasis and LN recurrence were 0% in m1 and m2, 9% in m3, 16% in sm1, 35% in sm2, and 62% in sm3 cases. The incidence of hematological recurrence was 0% in m1, m2, m3, and sm1 cases; 9% in sm2 cases; and 13% in sm3 cases. The overall risk of metastasis was 9% in m3, 16% in sm1, 38% in sm2, and 64% in sm3 patients. The 5-year disease-specific survival rates were 100% in m1, m2, and m3; 90.9% in sm1; 78.8% in sm2; and 68.6% in sm3 patients. Statistically, both lymphatic and venous invasion were selected as predictive markers for metastasis. In m3 patients, positivity for either of these had an odds ratio for metastasis of 7.333 (P = 0.093). Conclusions:Our study provides a precise assessment of the comprehensive risk of metastasis and feasible predictive markers for T1 ESCC.

Clinical and Pathologic Evaluation of the Effectiveness of Neoadjuvant Chemoradiation Therapy in Advanced Esophageal Cancer Patients

BackgroundChemoradiation therapy (CRT) has the strongest antitumor effect against local tumors of esophageal cancer; however, no standard strategy has yet been established to achieve a clinical complete response (CR) after CRT. The aim of this study was to clarify when a decision can be made to perform further treatment for a clinical CR.MethodsWe evaluated 78 patients that underwent an esophagectomy after neoadjuvant CRT in our department between 1998 and 2007. The study investigated the clinical and pathologic results of neoadjuvant CRT.ResultsOf the 78 cases, 19 (24.3%) were a pathologic CR (Grade 3). Pathologic CR could be estimated in only 3 of 8 clinical CR cases (37.5%). On the other hand, 12 (20.7%) of the 58 clinical partial response (PR) cases achieved pathologic CR. Likewise, 4 cases (36.4%) achieved pathologic CR among the clinical no change/progressive disease (NC/PD) patients.ConclusionsThe clinical evaluation for CRT does not reflect the pathologic effectiveness and, even if clinical CR was achieved, viable cancer cells were still present at the primary site in the majority of the population.

Synergistic antitumor effect of antiangiogenic factor genes on colon 26 produced by low-voltage electroporation.

Antiangiogenic factors are potent endothelial cell growth inhibitors that have been shown to inhibit angiogenesis in vitro and tumor growth in mice. We have demonstrated the synergistic antitumor effect of antiangiogenic genes (mouse angiostatin: pBLAST-mAngio; and mouse endostatin: p-BLAST42-mEndo XV) delivered to tumors by low-voltage electroporation in mouse colon 26 models. A synergistic antitumor effect was strongly suggested by in vivo tumor growth kinetics, as well as in survival studies with the mice. RT-PCR confirmed that the fragments of each gene were transferred by low-voltage electroporation in the tumor. Decreased microvessel density measurements in tumors also confirmed the efficacy of the synergistic antitumor effect of both genes. Significant growth inhibition was observed in mice treated with a 1:1 proportion of angiostatin and endostatin genes, and the order of the both genes transferred (first the endostatin gene, followed 1 week later by the angiostatin gene) had a profound inhibitory effect on tumor growth. These data suggest that in vivo delivery of antiangiogenic genes with low-voltage electroporation could be a possible therapeutic strategy for established solid tumors when both genes were applied in combination.

Possible involvement of antitumor immunity in the eradication of colon 26 induced by low-voltage electrochemotherapy with bleomycin.

Abstract.Purpose: The antitumor efficiency of electrochemotherapy using chemotherapeutic agents and high-voltage electric pulse has been reported. This study was done to define the precise nature of the involvement of antitumor immunity in the regression of tumor nodules in electrochemotherapy, and to evaluate the effectiveness of using low-voltage electroporation. Methods: Balb/c mice and Balb/c nu/nu nude mice were inoculated subcutaneously with Colon 26 cells or Meth A cells. Electrochemotherapy using bleomycin and low-voltage electroporation (CUY21) was performed as a treatment against tumor nodules. Results: Colon 26 tumors were eradicated in the mice given an intratumor (i.t.) injection of 500 μg bleomycin followed by treatment with electric fields ranging from 50 to 150 V/cm, with complete response rates ranging from 80% to 100%. The mice rejected inoculations of rechallenged Colon 26 cells, but not Meth A cells. In the Balb/c nu/nu nude mice, complete regression of the tumor was not seen after electrochemotherapy under the same therapeutic conditions that resulted in almost complete cure in the Balb/c mice. Conclusion: Our results suggest that the generation of T-cell-dependent, tumor-specific protective immunity might be involved in the process of tumor nodule regression in low-voltage electrochemotherapy.

Surgical advantages of gastric SMTs by laparoscopy and endoscopy cooperative surgery.

BACKGROUND/AIMS The treatment of gastric submucosal tumors (SMTs) is strictly surgical and enucleation of the tumor or wedge resection of the stomach is efficient to achieve R0 resection. Laparoscopic and endoscopic cooperative surgery (LECS) can be safely performed with adequate cutting lines. This study describes the initial 16 cases treated by LECS and evaluates the advantages by LECS for gastric SMTs retrospectively. METHODOLOGY Sixteen patients with gastric SMT underwent LECS from June 2007 to December 2010, their surgical data, clinical characteristics and surgical specimens of SMTs were compared. The surgical specimens of 9 gastric SMTs treated by laparoscopic wedge resection (LWR) were compared as a control. RESULTS The median (range) length of operation time, blood loss, hospital stay after surgery were minutes 172 (115- 220), <5mL (<5-115) and 10 days (6-17), respectively. The median (range) ratio of the longest diameter of the tumor divided by the longest diameter of the surgical specimen in LECS and LWR were 0.86 (0.625-1.0) and 0.69 (0.44-1.0), respectively (p=0.0189, Wilcoxon rank sum test). CONCLUSIONS LECS minimizes the surgical specimen while still providing sufficient surgical margins to successfully cure gastric SMTs.

Comparison between concentrations of amphotericin B in infected lung lesion and in uninfected lung tissue in a patient treated with liposomal amphotericin B (AmBisome)

Generally, the primary lesion of a mold infection is in the airway, an extravascular site. Therefore, the antifungal drug concentration at the actual tissue lesion of a mold infection is as important as in the blood compartment. Although our antifungal armamentarium has expanded recently, polyenes are still often needed in clinical practice because of their potent fungicidal activity and the rarity of resistance. Nevertheless, the distribution of amphotericin B (AmB) in infected lung tissue has not yet been evaluated. Using high-performance liquid chromatography analysis, we determined the concentrations of AmB in plasma and infected and uninfected tissues of resected lung simultaneously, in a patient with pulmonary aspergillosis treated with liposomal amphotericin B (L-AmB). The AmB concentration in the infected lesion of the lung was approximately 5.2 times higher than that in plasma and 3.7 times higher than in uninfected lung tissue. L-AmB accumulated in the infected lesion of the lung at a higher concentration. Although our data are from only one patient, they may be useful in helping to develop better strategies for the use of L-AmB against pulmonary fungal infections.

Salivary amylase activity is useful for assessing perioperative stress in response to pain in patients undergoing endoscopic submucosal dissection of gastric tumors under deep sedation

BackgroundAlthough endoscopic submucosal dissection (ESD) for patients with gastric tumors under the conditions of unconsciousness is considered to be minimally invasive, no objective assessment of the perioperative stress of ESD has yet been conducted. Today, stress levels can be easily and objectively assessed by monitoring salivary amylase activity (sAMY). We evaluated the perioperative changes in the sAMY in patients undergoing ESD and identified the causes of such changes.MethodsA total of 40 patients with gastric cancers/adenomas removed by ESD under general anesthesia (GA; n = 20) and under deep sedation (DS; n = 20) were enrolled. sAMY was measured using the enzyme analysis equipment, sAMY Monitor (NIPRO, Osaka, Japan) during the perioperative period of the ESD. Also, all patients were interviewed to determine their subjective stress level, using a questionnaire asking “How did you feel during ESD?”, with the choice of responses ranging from “did not wake up at all” to “I was awake and ESD was extremely stressful”.ResultsThe sAMY of the DS group increased soon after the start of ESD. Meanwhile, that of the GA group decreased just after the ESD started and was maintained at a stable level throughout the ESD. In response to the stress level questionnaire, all of the patients in the GA group and a majority of the patients in the DS group responded, “did not wake up at all”.ConclusionSympathetic agitation, expressed as an increase of sAMY, was absent in the GA group. Meanwhile, in the DS group, some patients showed high levels of sAMY which went down following the administration of an analgesic agent, thus suggesting that pain caused an elevation in the level of the stress and thereby induced an increase in sAMY. The measurement of sAMY is therefore considered to be useful for the assessment of analgesic status under DS.

The number of pathologic lymph nodes involved is still a significant prognostic factor even after neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma

The correlation between the number of pathologic metastatic LNs in patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (NACRT) and surgical outcome has rarely been reported. We evaluated the correlation between the number of pathologic metastatic lymph nodes (LNs) and the surgical outcome in ESCC after NACRT.

Treatment of Near-Infrared Photodynamic Therapy Using a Liposomally Formulated Indocyanine Green Derivative for Squamous Cell Carcinoma

Introduction Photodynamic therapy (PDT) is a less invasive option for cancer treatment that has evolved through recent developments in nanotechnology. We have designed and synthesized a novel liposome system that includes an indocyanine green (ICG) derivative, ICG-C18, in its bilayer. In addition to its use as an optical imager to visualize blood, lymphatic, and bile flow, ICG has also been used as an optical sensitizer. In the present report, we evaluate the use of our novel liposome system, LP-ICG-C18, in PDT for squamous cell carcinoma in an autologous murine model. Materials and Methods An excitation pulse beam (300 μJ/pulse) of a single band (800 nm) was used for sensitization. The cytotoxicity of the photodynamic therapy was evaluated in terms of cellular morphology changes, methyl thiazolyl tetrazolium (MTT) assay results, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining. We tested the enhanced permeability and retention effect of LP-ICG-C18 in tumor-bearing C3H/He mice using a near-infrared fluorescence imaging system and fluorescence microscopy. We also examined the antitumor effect of PDT by measuring tumor volume in tumor-bearing mice. Results Cell death and apoptosis were only observed in the PDT group receiving LP-ICG-C18. LP-ICG-C18 itself had no cytotoxic activity and showed good biocompatibility. LP-ICG-C18 accumulated on the tumor 24 hours after injection and was retained for approximately 3 weeks. Tumor cell apoptosis following PDT with LP-ICG-C18 was also observed under optical microscopy, MTT assay, and TUNEL staining. Conclusion These findings suggest that LP-ICG-C18 may be an effective intervening material in PDT for malignant disease.