Yukimasa Miyazawa

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.

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.

Expansion of Lung Vα14 NKT Cells by Administration of α‐Galactosylceramide‐pulsed Dendritic Cells

NKT cells, a novel murine lymphoid lineage bearing an invariant T cell receptor encoded by Vα14 and Jα281 gene segments, recognize a specific ligand glycolipid, α‐galactosylceramide (α‐GalCer) in a CDld‐dependent manner. Recent research has revealed that activated Vα14 NKT cells have dramatic antitumor effects against a wide variety of tumor cell lines in vivo and in vitro. Here, we demonstrate strong in vivo antitumor effects brought about by treatment with α‐GalCer‐pulsed dendritic cells in comparison with in vitro‐activated Vα14 NKT cells. Furthermore, we show a significant expansion of endogenous Vα14 NKT cells in the lung following the administration of α‐GalCer‐pulsed dendritic cells. The feasibility of immunotherapy with α‐GalCer‐pulsed dendritic cells is discussed.

Prognostic significance of CYFRA 21-1 in patients with esophageal squamous cell carcinoma

BACKGROUND CYFRA 21-1 has been reported as a useful tumor marker for esophageal carcinoma, but little information was reported about the clinicopathologic importance of CYFRA 21-1. The aim of this study was to analyze the clinicopathologic and prognostic significance of preoperative CYFRA 21-1 in patients with esophageal squamous cell carcinoma. STUDY DESIGN The CYFRA 21-1 levels were measured before surgery by enzyme-linked immunosorbent assays in 157 patients with primary esophageal squamous cell carcinomas using 3.5 ng/mL as the upper limit of normal. All patients underwent radical surgical procedures without any preoperative therapy. The association between the clinicopathologic factors assessed and the CYFRA 21-1 level was determined. The CYFRA 21-1 values were monitored after surgery in 45 available patients. The prognostic values were determined by multivariate analysis using Coxs proportional hazards model. RESULTS Thirty-one of the 157 patients (19.7%) had high CYFRA 21-1 levels (> or =3.5 ng/mL). CYFRA 21-1 levels were significantly increased in patients with large tumors (> or =40 mm, p = 0.009), deep tumors (T2-T4, p = 0.003), and node-positive tumors (p = 0.003). CYFRA 21-1 levels significantly decreased after surgery (p < 0.001). A high CYFRA 21-1 level before surgery was an independent prognostic factor for survival (p = 0.043). CONCLUSIONS A high CYFRA 21-1 level is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.

Analysis of Non-Genetic Risk Factors for Adverse Skin Reactions to Radiotherapy among 284 Breast Cancer Patients

ObjectvesWe analyzed non-genetic risk factors for adverse skin reactions to irradiation at 4 collaborating Japanese institutions, to design future investigation into genetic risk factors for adverse skin reactions to irradiation in a multicenter setting.MethodsFrom April 2001, 284 breast cancer patients, who underwent radiotherapy with breast-conserving surgery, were enrolled from 4 collaborating institutions in Japan. We graded skin reactions according to international scoring systems. Clinical factors were tested against adverse effects.ResultsGrade 1+ skin reactions were observed in 261 (92%) of the patients in less than 3 months, 118 (42%) at 3 months, and 29 (10%) at 6 months in the late phase. Univariate analysis of treatment risk factors (such as the use of a multi-leaf colimeter, wedge-filter, or immobilization device) for skin reactions revealed a significant association (p< 0.0001). After a variable selection procedure with logistic regression, the institution, operative procedure, and magnitude of photon energy remained significantly associated with acute skin reactions. Only the institution was an explanatory variable for skin reactions at 3 and 6 months in the final logistic model.ConclusionAfter stratification, substantial remaining variations in the occurrence of skin reactions of a given level suggested that individual genetic factors contribute markedly to individual radiosensitivity. Analysis of genetic factors associated with adverse effects would be possible by stratifying patients according to institution. Selection of eligible institutions, where appropriate treatment modalities could be performed, would also be possible when planning such a study.

Depressive disorders as psychiatric complications after obesity surgery

Three case reports of morbidly obese patients (two women and a man) who underwent vertical banded gastroplasty and who subsequently fell into depression, are presented here. The psychiatric diagnosis according to DSM‐III‐R (Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised), the eating pattern before obesity surgery, the past history of mental disorder, social adaptation before surgery, psychological gain from their obese state, and the presence of unrealistic expectations of obesity surgery were investigated. Case 1 was diagnosed postoperatively as having a major depressive episode without a personality disorder. Case 2 was diagnosed postoperatively as having a major depressive episode. Case 3 had a depressive disorder not otherwise specified. Cases 2 and 3 had a social phobia with comorbidity of personality disorders. Binge eating disorder was confirmed in all patients before obesity surgery. There were differences between case 1 and cases 2 and 3 based on the presence of personality disorder and the time of onset of depression. When some psychiatric characteristics are confirmed in obese patients, obesity surgery should be undertaken more prudently because the patients may manifest depression postoperatively. The pre‐operative psychiatric assessment is essential for a decision on indication of obesity surgery.

Diffusion-weighted MRI as an adjunct to mammography in women under 50 years of age: an initial study.

To evaluate diffusion‐weighted magnetic resonance (DW) imaging as an adjunct to mammography for the detection of small invasive breast cancer.

CHAP31 Induces Apoptosis Only via the Intrinsic Pathway in Human Esophageal Cancer Cells

Objective: The antitumor mechanism of histone deacetylase (HDAC) inhibitors differs from conventional antitumor agents. HDAC inhibitors may be effective as novel therapeutic agents for esophageal squamous cell carcinoma (ESCC). This study describes the antiproliferative activity of CHAP31, a novel HDAC inhibitor. Furthermore, the molecular mechanism of CHAP31-induced apoptosis was investigated in ESCC. Methods/Results: The antitumor activity of CHAP31 was tested in esophageal cancer cell lines (T.Tn and TE2), and potent antitumor activity was observed in vitro and in vivo. In addition, CHAP31 induced apoptosis in esophageal cancer cells. Next, the mechanisms of CHAP31-induced apoptosis were examined using quantitative real-time RT-PCR and Western blotting. No processing of caspase 8 was observed, but CHAP31 induced the cleavage of caspase 9 and up-regulation of the Bax/Bcl-2 protein ratio. Conclusion: This study provides new and important information on the potent antitumor activity of CHAP31 and the apoptotic pathway induced by CHAP31 in human esophageal cancer cell lines T.Tn and TE2. In contrast to previous reports showing that apoptosis induced by HDAC inhibitors includes the extrinsic pathway, in our study, apoptosis induced by CHAP31 in the human esophageal cell lines T.Tn and TE2 involved only the intrinsic pathway.

Combined Effects of p53 Gene Therapy and Leptomycin B in Human Esophageal Squamous Cell Carcinoma

Background: p53 gene therapy has been examined in several clinical trials, however, the results of those trials have mostly been unsatisfactory due to the low efficacy of this therapy. Leptomycin B (LMB) is an antibiotic originally isolated from Streptomyces that has the ability to inhibit the export of proteins containing a nuclear export signal from the nucleus to the cytoplasm. Currently, it has been shown that p53 protein has a nuclear export signal. In this study, we assessed whether LMB augments the transduced p53 gene effect. Methods: Antiproliferative effect of LMB was assessed in human esophageal squamous cancer cell lines. Accumulation of p53 protein into the nucleus by LMB was observed by fluorescence microscopy. The combined effect of p53 and LMB was evaluated in in vitro experiments. Results: LMB induced cell death in a dose-dependent manner and p53 drastically accumulated in the nucleus after LMB treatment. The combinatory treatment of p53 gene and LMB significantly increases the efficiency compared to either agent alone. Conclusions: Our findings suggest that LMB has a potent ability to augment the effect of the tumor suppressor p53 in esophageal squamous cancer cell lines and that it is a promising component in p53 gene therapy.

Primary Non-Hodgkin's Lymphoma of the Male Breast: A Case Report.

A 69-year-old Japanese man presented with bilateral gynecomastia and a soft, mobile and clearly defined mass beneath the left nipple. A round radiopaque mass was revealed on mammography. The tumor was homogeneous, hypoechoic and measured 2.4X3.9 cm on ultrasonography. Based on a diagnosis of malignant lymphoma by needle aspiration cytology, a modified radical mastectomy with ipsilateral axillary lymph node dissection was performed. Malignant diffuse large B-cell type lymphoma was diagnosed histologically. Whole body examinations revealed no evidence of other tumors. Three courses of adjuvant CHOP therapy were subsequently performed. The patient is free of recurrence 12 months after surgery.Primary non-Hodgkin’s lymphoma (NHL) of the male breast is extremely rare. The occurrence of lymphoma in this patient could be related to elevated estrogen levels.