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A 46-year-old woman with a sore throat was diagnosed with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma that had spread from the piriform fossa to the cervical esophagus. Tracheoesophageal fistula developed after induction chemotherapy. Because conservative repair was not applicable, intensified chemotherapy, including autologous stem cell transplantation was performed with the fistula remaining open. Laryngopharyngectomy and cervical esophagectomy were performed 6 months after transplantation. The optimal strategy for refractory lymphoma with active tracheoesophageal fistula remains undetermined. To the best of our knowledge, this is the first report describing the successful treatment of a patient with tracheoesophageal fistula who received high-dose chemotherapy supported by autologous stem cell transplantation.

The case was a 55-year-old woman. She have been pointed out von Recklinghausen's disease for several years. She was referred to our hospital due to multiple abdominal tumor and severe anemia. Enhanced CT examination revealed multiple intraabdominal tumors with central necrosis. The tumors diagnosed mesenchymal tumors associated with von Recklinghausen's disease, and tumor resection was indicated under laparotomy. Tumors were resected together with small and large bowel. The tumor in the pelvic space was resected together with the uterus and right ureter. She was discharged without any postoperative complications at 15 days after the operation. Because immunostaining was positive for CD34, c-kit and DOG1 and Ki-67-positive cells were 18%, the tumors were diagnosed with high-risk GIST for small bowel.

A 56-year-old woman complaining of right lower abdominal pain was admitted to our hospital. An abdominal computed tomography showed the enlarged appendix tip and a high density area around the appendix to retroperitoneum. The patient was diagnosis with acute appendicitis and underwent emergency laparoscopic appendectomy. Histopathological findings of the resected specimens revealed a component with signet ring cell carcinoma morphology that was positive for neuroendocrine markers by immunohistochemical staining, which led to the diagnosis of goblet cell carcinoid(GCC)of appendix. GCC cells were found to infiltrate the surrounding serosa and Ly positive. An additional laparoscopic ileocecal resection with D3 dissection was performed. In the appendix GCC, additional resection is considered because the lymph node metastasis rate increases(SS/13%)as the depth of wall progresses. Appendiceal tumors including GCC may develop acute appendicitis and may be followed by additional resection. Therefore, it is important to consider how to deal with the first surgery.

We have sometimes experienced technical difficulty performing thoracoscopic esophagectomy because of the position of the descending aorta or width of the mediastinal space. In this study, we retrospectively investigated predictive preoperative factors that influence the procedure of thoracoscopic esophagectomy with a focus on the position of the descending aorta and width of the mediastinal space. Ninety-five patients who underwent thoracoscopic esophagectomy for esophageal cancer by two specialists were included in this study. Thirty patients in whom both the operation time and blood loss in the thoracic region exceeded the median were categorized to the difficult group. The remaining 65 patients were categorized into the common group. During the evaluation of the position of the descending aorta, we measured the aorta–vertebra angle at the level of the left inferior pulmonary vein. During the evaluation of the width of the mediastinal space, we measured the sternum–vertebra distance at the level of the tracheal bifurcation. A forward stepwise logistic regression analysis revealed the following independent predictive factors of the technical difficulty of thoracoscopic esophagectomy: aorta–vertebra angle (≥ 30°), sternum–vertebra distance (

We analyzed retrospectively the difference in treatment selection and prognosis according to timing of recurrence after radical resection of esophageal cancer. Of 190 patients who underwent radical esophagectomy for esophageal cancer from April 2010 to December 2017, 56 patients(29.5%)had recurrent diseases during the postoperative periods. These cases were divided into 27 cases with recurrence diagnosed less than 180 days after initial surgery(Group A)and 29 cases with recurrence diagnosed more than 180 days(Group B). Although there was no difference in the pathological staging, preoperative treatment, and type of recurrence between the 2 groups, there were significantly more cases with symptomatic recurrence in Group A. Surgical intervention was possible in 1 case in Group A and 10 cases in Group B, respectively. There was significantly more in Group B. Second-line treatment was possible in only 5 cases in Group B. Survival after recurrence was tend to have better in Group B. There are few cases who indicated surgical intervention and second-line treatment in early recurrence cases after radical esophagectomy for esophageal cancer, and the prognosis is poor in such cases.

We investigated the clinical outcomes of salvage thoracoscopic esophagectomy for residual or recurrent cases after radical radiochemotherapy for cStage Ⅳa esophageal cancer. Thoracic procedure was started thoracoscopically in all cases, but converted to thoracotomy in 2 cases. The operation time was 315 minutes and the blood loss was 300 mL. Lymph node metastasis was diagnosed in 5 cases, and 2 cases were finished in R1or 2. Nine cases died of recurrence and 1 case died of pneumonia. The 2-year and 5-year survival rates(OS)of all cases were 46.1% and 28.3%, respectively. R1,2 cases and pN+ cases had significantly poor prognosis. Surgical treatment after radical radiochemotherapy for cStage Ⅳa esophageal cancer can be safely performed thoracoscopically. If R0 is not obtained, the long-term prognosis cannot be expected, and selection of R0 resectable cases is important.

Neoadjuvant chemotherapy (NAC) involving two cycles of cisplatin plus fluorouracil is recommended in Japan as a standard treatment for resectable, locally advanced esophageal squamous cell carcinoma (ESCC). We have encountered patients who were administered incomplete chemotherapy because of adverse events or the patient’s refusal of treatment. Here, we retrospectively investigated the influence on perioperative outcomes and long-term prognosis of patients with ESCC who underwent complete (two cycles) or incomplete (one cycle) NAC. We retrospectively investigated 133 patients with locally advanced ESCC of the thoracic esophagus who underwent NAC. We compared the perioperative results and prognoses of patients who underwent complete or incomplete NAC because of adverse events or the patient’s refusal of treatment. Of 133 patients, 37 patients did not receive the second cycle of NAC; the remaining 96 patients received the second cycle of NAC as scheduled. There were no significant differences in the clinical backgrounds, surgical results, or operative morbidity rates between the groups. Patients in both groups were similarly administered postoperative chemotherapy regimens. There was no significant difference in disease-free survival or overall survival. We suggest that perioperative outcomes and long-term prognosis of patients with locally advanced ESCC were not significantly influenced, even if the patients did not receive a complete cycle of NAC. When certain adverse events occur after the first cycle of NAC, we believe that it is nevertheless possible to discontinue chemotherapy.

Neoadjuvant chemotherapy (NAC) with cisplatin and fluorouracil is the recommended standard treatment for resectable locally advanced esophageal cancer (EC) in Japan. We investigated the effects of NAC on the safety and feasibility of thoracoscopic esophagectomy with total mediastinal lymphadenectomy for EC. This retrospective study analyzed data from 225 consecutive patients who underwent thoracoscopic esophagectomy with lymph node dissection between April 2007 and December 2015. Patients with clinical stage IB, IIA, IIB, IIIA, or IIIB EC, and no active concomitant malignancy were included. We compared intraoperative outcomes, and postoperative morbidity and mortality between patients who received NAC (n = 139; NAC group) and patients who did not (n = 86; non-NAC group). Preoperative laboratory data revealed that anemia, thrombopenia, and renal dysfunction were more common in the NAC group than in the non-NAC group. There were no differences between the groups in operating times, blood loss, number of dissected lymph nodes, overall complication rates, or length of postoperative hospital stay. Based on our findings, thoracoscopic esophagectomy is safe and effective for locally advanced EC, even after NAC.

A 73-year-old man was diagnosed with essential thrombocythemia and treated with acetylsalicylic acid and hydroxyurea for 15 years. He was referred to our hospital for treatment of esophageal cancer detected by endoscopy. The cancer stage was T1N1M0, cStage IIB according to the classification of the Union for International Cancer Control, 7th edition. After administering two courses of preoperative chemotherapy (5-fluorouracil + cisplatin), the patient underwent video-assisted thoracoscopic radical esophagectomy. Hydroxyurea administration was discontinued during anticancer therapy and restarted to control the platelet count. Heparin was continuously infused during the perioperative period, and hydroxyurea was restarted through a jejunostomy tube on the postoperative day 2. No thrombosis or hemorrhage developed, and the patient was discharged from the hospital on the postoperative day 33. This is the first case report of video-assisted thoracoscopic radical esophagectomy for esophageal cancer in a patient with essential thrombocythemia.

Aberrant hypermethylation of specific genes is present in esophageal squamous cell carcinomas (ESCCs). Such hypermethylation is also present in normal-appearing esophageal mucosae of ESCC patients and is considered to contribute to the formation of a field for cancerization. On the other hand, the presence of global hypomethylation in ESCCs or in their background esophageal mucosae is unknown. We collected 184 samples of esophageal mucosae (95 normal mucosae from healthy subjects, and 89 non-cancerous background mucosae from ESCC patients) and 93 samples of ESCCs. Methylation levels of repetitive elements (Alu, LINE1) and cancer/testis antigen genes (NY-ESO-1, MAGE-C1) were measured by bisulfite pyrosequencing and quantitative methylation-specific PCR, respectively. Methylation levels of Alu, LINE1, NY-ESO-1, and MAGE-C1 were significantly lower in ESCCs than in their background and normal mucosae. Also, in the background mucosae, a significant decrease of the Alu methylation level compared with the normal mucosae was present. In ESCCs, methylation levels of the two repetitive elements and the two cancer/testis antigen genes were correlated with each other. This is the first study to show the presence of global hypomethylation in ESCCs, and even in their non-cancerous background mucosae. Alu hypomethylation might reflect the severity of an epigenetic field for cancerization.

Massive bleeding from large vessels is a serious and life-threatening complication after radical esophagectomy. Here, we present the rare case of patient survival following two episodes of massive bleeding from a tracheo-brachiocephalic artery fistula after salvage surgery for cervical esophageal cancer following definitive chemoradiation. During the first episode of bleeding, the damaged part of the brachiocephalic artery was transected with an extra-anatomical arterial bypass (right femoro-axillo artery bypass graft) to maintain the arterial blood flow to the brain and the free jejunal graft. During the second bleeding, the distal stump of the brachiocephalic artery was reclosed. During both episodes of bleeding, the musculocutaneous flap was effectively employed to seal the stumps of the brachiocephalic artery and fill the dead space. Finally, the patient was discharged 351 days after the first surgery. (132/150).

Background The development of minimally invasive surgery has yielded many benefits, therefore the number of patients undergoing thoracoscopic radical esophagectomy (TRE) for esophageal cancer has been increasing worldwide. However, in the Japanese nationwide web-based database report, the incidence of recurrent laryngeal nerve (RLN) paralysis and overall morbidity were significantly higher in the TRE group than in the open esophagectomy group. In recent years, intraoperative nerve monitoring (IONM) is commonly being used in thyroid and parathyroid surgery in many centers. We tried to determine the feasibility and effectiveness of IONM of RLN during upper mediastinal lymph node dissection in TRE. Methods All 628 patients who underwent TRE in the left lateral decubitus position at Osaka City University Hospital between May 1995 and February 2018 were enrolled in the present study. We introduced IONM using NIM® (Medtronic) during TRE from October 2016 at our hospital. We divided retrospectively the patients into two groups: IONM group (TRE with IONM of RLN; n = 49) and No-IONM group (TRE without IONM of RLN; n = 579). Diagnosis of RLN paralysis was performed using laryngoscopy. The feasibility of IONM during TRE and the incidence of postoperative RLN paralysis were compared with those in No-IONM group. Results IONM could be performed for 46 patients (93.9%) in IONM group. Three patients (6.1%) could not keep single-lung ventilation using a single lumen tracheal tube with a bronchial blocker and needed to replace a tracheal tube by a double lumen tube during TRE. The incidence of postoperative RLN paralysis (CD≧ 1; CD; Clavien-Dindo classification of surgical complications) was 17.4% in IONM group and 30.2% in No- IONM group. There was a significant difference in the incidence of postoperative RLN paralysis (P Conclusion IONM of RLN during TRE is technically feasible. The introduction of standardized IONM of RLN during TRE is able to reduce the incidence of postoperative RLN paralysis. Disclosure All authors have declared no conflicts of interest.

In DNA methylation microarray analysis, quantitative assessment of intermediate methylation levels in samples with various global methylation levels is still difficult. Here, specifically for methylated DNA immunoprecipitation-CpG island (CGI) microarray analysis, we developed a new output value. The signal log ratio reflected the global methylation levels, but had only moderate linear correlation (r = 0.72) with the fraction of DNA molecules immunoprecipitated. By multiplying the signal log ratio using a coefficient obtained from the probability value that took account of signals in neighbouring probes, its linearity was markedly improved (r = 0.94). The new output value, Me value, reflected the global methylation level, had a strong correlation also with the fraction of methylated CpG sites obtained by bisulphite sequencing (r = 0.88), and had an accuracy of 71.8 and 83.8% in detecting completely methylated and unmethylated CGIs. Analysis of gastric cancer cell lines using the Me value showed that methylation of CGIs in promoters and gene bodies was associated with low and high, respectively, gene expression. The degree of demethylation of promoter CGIs after 5-aza-2'-deoxycytidine treatment had no association with that of induction of gene expression. The Me value was considered to be useful for analysis of intermediate methylation levels of CGIs.

食道癌術後には凝固異常が発症することが知られている。この凝固異常に対しては，現在までステロイドなどさまざまな薬剤投与が試みられてきた。今回われわれは，好中球エラスターゼの特異的阻害剤（シベレスタットナトリウム，以下SN）投与の食道癌術後の凝固能におよぼす影響について検討した。対象は食道癌切除再建を一期的に行った41例で，これら症例を術後SNを投与した21例（SN+群）と，SNを投与しなかった20例（SN-群）に分けた。SN+群でSNを，術直後より0.2mg/kg/hrで術5病日まで持続的に投与した。全例で術直前にメチルプレドニゾロン（500mg）を投与し，術7病日まで血小板数・FBG·FDP·D-Dimer·AT3·TAT·APTT·Protein C・α2PIを経時的に測定した。血小板数・FBG·FDP·D-Dimer·TATの変動には両群に差がなかった。AT3とProtein Cは術2·3病日でSN+群が有意に高値で，α2PIは術3病日でSN+群が有意に高値であった。APTTは，術3病日にSN-群で有意に高かった。食道癌術後管理におけるエラスターゼ阻害剤投与は食道癌術後の凝固異常状態を制御し，早期に回復させることが可能である。

We report a case of pneumocystis pneumonia (PCP) during adjuvant chemotherapy for advanced sigmoid colon cancer. A 70-year-old Japanese man was referred to our hospital after complaining of bloody stools. He was diagnosed with advanced sigmoid colon cancer, T2N2aM1b, Stage IV B. After 3 cycles of mFOLFOX6 plus panitumumab as first-line chemotherapy, he received FOLFIRI plus bevacizumab as second-line chemotherapy because of progressive disease. Aprepitant and steroids were administered as antiemetic agents for a short period during each chemotherapy session. During the 2 cycle of FOLFIRI plus bevacizumab, he developed a high fever without respiratory symptoms. Chest CT revealed ground-glass opacities in both the lungs. We first treated him with antibiotics (PIPC/TAZ plus GRNX), suspecting bacterial pneumonia. However, based on the elevation of serum b -D-glucan (148 pg/mL), we diagnosed PCP and initiated SMX/TMP in addition to PIPC/TAZ. The inflammation promptly decreased, and follow-up chest CT revealed the disappearance of the ground-glass opacities. If a patient develops a fever or respiratory symptoms during a course of chemotherapy, we should consider the possibility of PCP and perform careful examinations.

Esophageal anastomotic leakage is one of the most fatal complications after esophagectomy and increases the hospitalization length. We aimed to identify a convenient clinical marker of anastomotic leakage in the early postoperative period.In total, 108 patients who underwent esophagectomy were retrospectively screened, and 96 were used to validate the overall results. All 108 patients underwent physical examinations and determination of their white blood cell count, C-reactive protein level, platelet count, fibrinogen level, fibrin degradation product level, and antithrombin III level until postoperative day 6.Anastomotic leakage occurred in 21 of the 108 patients (median detection, 8 days). The C-reactive protein level on postoperative day 3 and fibrinogen level on postoperative day 4 in the leakage group were significantly higher than those in the nonleakage group. Receiver operating characteristic curves for detection of anastomotic leakage were constructed; the cutoff value of C-reactive protein on postoperative day 3 was 8.62 mg/dL, and that of fibrinogen on postoperative day 4 was 712 mg/dL. Anastomotic leakage occurred in 23 of the 96 patients in the validation group. There was a significant difference between the leakage and nonleakage groups when the C-reactive protein threshold on postoperative day 3 was set at 8.62 mg/dL. However, there was no difference between the groups when the fibrinogen threshold on postoperative day 4 was set at 712 mg/dL.The C-reactive protein level on postoperative day 3 is a valuable predictor of anastomotic leakage after esophagectomy and might allow for earlier management of this complication.

成因の異なる良性食道気道瘻3例を経験した。症例1: 63歳，男性。食道癌に対し，60Gy照射した1年後に咳嗽と胸痛が出現した。内視鏡で食道と左主気管支間に瘻孔を認めたが，ステントにて瘻孔を遮断できず，右開胸下に瘻孔辺縁の食道壁によるパッチ閉鎖および食道癌根治術を行った。瘻孔部に癌遺残はなく，放射線傷害による食道気管支瘻と診断した。症例2: 56歳，男性。胆嚢摘出術後に左肺炎を繰り返した。胸部X線で左下肺野の肺炎像を，食道造影で中部食道の憩室から左下気管支へ造影剤の流入を認めた。左開胸下に憩室と左主気管支間に索状物，また左肺下葉の器質化を認めた。Braimbridge I型の先天性食道気管支瘻と診断し，憩室切除と左肺下葉切除を行った。症例3: 31歳，男性。交通事故での胸部外傷後，摂食時に咳嗽が出現した。内視鏡で膜様部欠損による食道気管瘻を認めた。外傷性食道気管瘻と診断し，右開胸下に瘻孔辺縁の食道壁によるパッチ閉鎖を行い，食道壁はGambee縫合で閉鎖した。良性食道気道瘻では食道や気道の狭窄を伴うことが少なく，ステントによる瘻孔遮断は無効なことが多い。手術による瘻孔閉鎖が有効である。

More than 15 years have passed since thoracoscopic surgery was first employed in Japan as a treatment for esophageal cancer with curative intent. Because of the proliferation of techniques that can be used to obtain an adequate operative field, such as hand assist, placing the patient in the prone position, etc., the number of approaches to thoracoscopic surgery has been increasing, contrary to expectations of standardization. The technique of mediastinal dissection has been refined with increasing knowledge of microanatomy, which can be clarified under the magnified view provided in thoracoscopic surgery. Comparable pulmonary function and survival are achieved after both thoracoscopic surgery and open-chest surgery. The accreditation board of the Japan Society for Endoscopic Surgery is now standardizing the thoracoscopic technique. To avoid surgical mistakes, thorough knowledge and adherence to the proper indications are essential.

A 77-year-old male with thoracic esophageal cancer (cT3N3M0, Stage III) received nedaplatin at 80mg/m2 for 1 day and 5-fluorouracil at 800mg/m2 for 5 days as neoadjuvant treatment. On the fifth day of treatment, he lapsed into a coma (Japan Coma Scale 30), and his serum sodium concentration was found to be decreased to 116mEq/L. We concluded hyponatremia due to SIADH (syndrome of inappropriate secretion of antidiuretic hormone) induced by chemotherapy based on the fact that the patient had no finding of dehydration, particular history of related disorders, serum hypoosmolality accompanied by urine hyperosmolality and persistent urinary sodium excretion. We treated him with fluid restriction, sodium supplement and administration of loop diuretic. Then he regained consciousness and appropriate serum sodium level. Thereafter, hyponatremia was corrected without recurrence, and the patient underwent radical esophagectomy safely. He has been in good condition without recurrence of esophageal cancer after surgery.

The presence of lymph node metastasis in esophageal squamous cell carcinoma (ESCC) patients is a critical factor for decision of treatment strategy. However, there have been no molecular markers to assess lymph node metastasis. In this study, we aimed to identify CpG islands (CGIs) whose DNA methylation statuses are associated with the presence of lymph node metastasis. A total of 96 ESCCs were divided into a screening set (n = 48) and a validation set (n = 48). Genome-wide methylation analysis was performed by methylated DNA immunoprecipitation-CGI microarray analysis. Methylation levels were analyzed by quantitative methylation-specific PCR (qMSP). Genome-wide methylation analysis identified 25 CGIs differentially methylated between 8 ESCCs with lymph node metastasis and 4 without. In the screening set, 7 CGIs had significantly different methylation levels (P

Many patients who undergo distal gastrectomy develop remnant gastritis. The diagnosis of remnant gastritis is commonly established endoscopically. This report describes the correlation between endoscopic and histological findings of inflammatory changes in the remnant gastric mucosa.Ninety-seven patients who underwent curative distal gastrectomy for gastric cancer, with radical lymphadenectomy, were studied. Endoscopy was performed 12 weeks after surgery. Patients with marked redness, erosion, or edema of the gastric remnant, as seen by endoscopy, were judged to have remnant gastritis, and were divided into group P (positive) and group N (negative). Histological remnant gastritis was evaluated with the neutrophil infiltration score based on the updated Sydney System for endoscopically taken biopsies. Cyclooxygenase (COX)-2 expression was evaluated immunohistochemically.There was no difference in neutrophil infiltration or COX-2 expression scores between the patients in groups P and N. There was a significant correlation between neutrophil infiltration score and COX-2 expression score (p0.001).Endoscopic diagnosis of remnant gastritis was not correlated with histological findings. Histological remnant gastritis had significant correlation with COX-2 expression score, which was induced by inflammation. Therefore, proper diagnosis of remnant gastritis should be based on histological examination.

Helicobacter pylori is a carcinogen for gastric cancer. There have been few reports on carcinogenesis about H. pylori infection in the gastric remnant after distal gastrectomy. The relationship between carcinogenesis and H. pylori infection was studied by means of inflammation and oxidative stress.Ninety-seven patients who had undergone curative distal gastrectomy for gastric cancer were studied. All patients underwent endoscopic examination 3 months after surgery. The presence of H. pylori was determined using urease rapid test, hematoxylin-eosin staining, and immunohistochemical staining. Fifty-one patients were positive (group A) and 46 patients were negative (group B). The grades of remnant gastritis were scored by updated Sydney System. 8-Hydroxydeoxyguanosine (8-OHdG) as an oxidative stress marker, was analyzed immunohistochemically, and graded in 4 grades.Both the neutrophil infiltration score and 8-OHdG expression score was higher in group A than group B (p = 0.03 and 0.05). The correlation between the 8-OHdG expression score and the neutrophil infiltration score was significant (p = 0.02).As gastritis is related to oxidative stress, H. pylori infection is suspected to play an important role in carcinogenesis in the gastric remnant.

Thoracoscopic esophagectomy for cancer has become common in the 10 years after the introduction of the procedure, with advances in instrumentation and techniques. Thoracoscopic surgery is associated with the advantage of preserving pulmonary function and reducing pulmonary complications by reducing chest wall injury and blood loss. Although it cannot be evaluated subjectively, understanding the microanatomy under a magnified view, education through viewing on a monitor, and the ability to reproduce the whole procedure are advantages. However, to perform lymph node dissection as efficiently as in open surgery, substantial learning of the procedure is necessary. To steepen the learning curve, sharing and disclosing knowledge and information are essential, as well as direct instruction and hands-on seminars given by skilled experts.

Aberrant DNA methylation is deeply involved in prostate carcinogenesis. However, inducers of aberrant DNA methylation in the prostate are almost unknown. Here, we investigated whether androgen excess can induce aberrant DNA methylation or not, using a rat prostate cancer model. First, by analysis of reported data of expression microarray after treatment of a prostate cancer cell line with a demethylating agent, we isolated two marker genes (Mmp23, Nkx3.1) whose promoter CpG islands were aberrantly methylated in testosterone and 3,2′-dimethyl-4-aminobiphenyl-induced invasive adenocarcinomas. These two genes and three genes previously isolated (Aebp1, Amn1, Tgfbr2) [Yamashita et al. Cancer Res. 2008] were used as markers. Then, we analyzed temporal profiles of DNA methylation levels of the five genes in the dorsolateral lobe of rats treated with excessive androgen. Testosterone was administrated every five weeks for 15, 30, 40 and 50 weeks from six weeks old by subcutaneous implantation of a Silastic tube containing 40 mg testosterone propionate. Aberrant DNA methylation of two genes (Amn1, Mmp23) was gradually induced during the testosterone treatment while that of the other three genes was not. The former two genes had lower mRNA expression levels in the normal prostate than the latter three genes, which was in accordance with the known fact that genes with low transcription are susceptible to DNA methylation. Third, we investigated molecular mechanisms for aberrant DNA methylation induction by androgen excess. Androgen excess did not induce mRNA expression of DNA methyltransferases; Dnmt1, Dnmt3a or Dnmt3b in the rat prostrate. As for histone modifications, it did not induce significant changes in either H3K4me3 or H3K27me3 levels of the five genes methylated in rat prostate cancer. In contrast, it induced infiltration of lymphocytes and neutrophils in the prostate. Temporal profiles of expression levels of specific inflammation-related genes (Cxcl2, Il1b, Nos2 and Tnf) paralleled the methylation levels of Amn1 and Mmp23. Androgen excess did not induce bacterial infection as determined by copy number of bacterial DNA, but induced increase in Ki67-positive cells in regions with and without infiltration of inflammatory cells. The inflammatory response, known as a major mechanism for aberrant DNA methylation induction, along with cell proliferation was likely to be the cause of aberrant DNA methylation induction in the rat prostate with androgen excess. These results demonstrated that androgen excess can induce aberrant DNA methylation in the prostate, and suggested that inflammatory response underlies aberrant DNA methylation induction by androgen excess. Citation Format: Satoshi Yamashita, Satoru Takahashi, Yasunori Matsuda, Ken Gyobu, Toshikazu Ushijima. Androgen excess induces aberrant DNA methylation in the prostate. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5375. doi:10.1158/1538-7445.AM2013-5375