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A 51-year-old woman with a 3-year history of diplopia was admitted to our hospital. Repetitive stimulation of the right median nerve revealed decreasing hand muscle responses. Edrophonium chloride administration alleviated the symptoms. The serum antiacetylcholine receptor antibody level was 3.3 nmol/l; thus, myasthenia gravis was diagnosed. A chest roentgenogram revealed a left inferior mediastinal mass, and a chest computed tomographic scan revealed a fat density mass partly containing soft tissue areas in the left side of the anterior mediastinum. Median sternotomy and extended thymectomy were performed. The pathology examination of the tumor revealed mature adipose tissue including islands of thymic tissue containing Hassall's corpuscles, without germinal centers. The tumor was a thymolipoma of the anterior mediastinum. Her postoperative course was good, and she is doing well at 1 year postoperatively.

Although some beneficial effects of surgical treatments for pulmonary or hepatic metastases from colorectal carcinoma have been reported, identifying candidates for these aggressive surgical procedures is controversial. In this study, patients with pulmonary metastases from colorectal carcinoma, particularly those with pulmonary and hepatic metastases, were retrospectively analyzed. Forty-six patients who had undergone complete resection for pulmonary metastases from colorectal carcinoma were retrospectively analyzed. The median follow-up period after pulmonary resection was 26 months, and the 5-year postoperative survival rate was 34%. The 5- and 10-year survival rates of patients with pulmonary metastasis alone, metachronous pulmonary metastasis after liver metastasis, and synchronous metastasis to the liver and lung were 75%, 75%, and 25% and 25%, 38%, and 0%, respectively, when calculated from the time of primary colorectal resection (P < 0.01). Patients with synchronous metastases had a poorer prognosis than did the patients in the other two groups. Surgical treatments for patients with pulmonary metastasis alone or metachronous metastasis can provide a beneficial outcome. Patients with synchronous metastasis have a poor prognosis, and effective pre- and postoperative systemic treatments should be considered to prolong their survival.

We present 2 resected cases of thymic tuberculosis, which had been preoperatively diagnosed as invasive thymoma, using a thallium-201 ((201)Tl) single photon emission computed tomography ((201)Tl SPECT). [Patient 1] A 74-old-male with a 32-year history of steroid therapy for rheumatic arthritis was diagnosed with an anterior mediastinal tumor by routine chest CT scans after onset of myocardial infarction. [Patient 2] A 56-old-female with a 28-year history of diabetes mellitus presented with a dry cough. A chest CT demonstrated an anterior mediastinal tumor. Neither patient showed pulmonary infiltrations on chest x-ray. (201)Tl SPECT was undertaken for each patient. Abnormal findings could not be detected on a planar image of the scintigraphy; however, on SPECT images accumulations of (201)Tl were clearly detected in the anterior mediastinal mass and a thymoma was thus suspected in each case. Total thymectomy was carried out in each case and the mass then diagnosed as caseous granuloma in the thymus. Both patients are well without recurrence after operation. In patients with a (201)Tl SPECT positive anterior mediastinal tumor associated with an immunologically deficient status, and with negative findings in planar images on thallium scintigraphy, the possibility of thymic tuberculosis should be considered.

A 73-year-old male presented with bloody sputa for a month. Chest computed tomography (CT) showed a large mass about 7 cm in diameter in the right lower lobe. Bronchoscopic curette cytology revealed class V and a suspected adenocarcinoma, although a systemic evaluation demonstrated no metastatic lesion. The patient underwent a right lower lobectomy and mediastinal dissection. A biphasic pulmonary blastoma was histologically diagnosed by a characteristic finding that it was mainly constituted of immature tumor tissue that had both epithelial and mesenchymal components. No mediastinal lymph node metastasis was proven. Stage T2N0M0 disease was diagnosed, and the patient chose not to undergo postoperative adjuvant chemotherapy; he remains well without recurrence 36 months after the operation.

Pulmonary hamartoma is a common benign neoplasm that is usually asymptomatic and that arises in the periphery of the lung. However, when the tumor is growing without showing characteristic findings of hamartoma, such as involving calcification, fat density, and chondromatous contents in chest X-rays or computed tomography, the diagnosis is sometimes that problematic and definitive histological diagnosis should be established. We herein report a case with a massive hemoptysis 10 days after a successful transbronchial biopsy. A 69-year-old man who underwent mitral valve plasty 6 years earlier presented a left lung shadow during a routine chest X-ray. The shadow was seen to be growing by a series of chest X-rays. A week after warfarin had been stopped, a bronchoscopic biopsy was performed. No bronchial hemorrhage was observed during the procedure, and warfarin was not restarted. The patient began noticing bloody sputa once or twice a day, and 10 days after the biopsy, 400 mL of hemoptysis was suddenly disgorged. An emergency left upper lobectomy of the lung was performed, and the hemoptysis soon disappeared postoperatively. The patient is well without respiratory symptoms 36 months after the surgery.

We report a case of pouchitis and pre-pouch ileitis, and inflammation in the neo-terminal ileum proximal to the pouch, developed after restorative proctocolectomy for ulcerative colitis. A 35-year old female presented with fever and abdominal pain five weeks after ileostomy closure following proctocolectomy. Computed tomography showed collection of feces in the pouch and proximal ileum. A drainage tube was placed in the pouch perianally, and purulent feces were discharged. With antibiotic treatment, her symptoms disappeared, but two weeks later, she repeatedly developed fever and abdominal pain along with anal bleeding. Pouchscopy showed mucosal inflammation in both the pouch and the pre-pouch ileum. The mucosal cytokine production was elevated in the pouch and pre-pouch ileum. With antibiotic and corticosteroid therapy, her symptoms were improved along with improvement of endoscopic inflammation and decrease of mucosal cytokine production. The fecal stasis with bacterial overgrowth is the major pathogenesis of pouchitis and pre-pouch ileitis in our case.

The foraging strategy of many animals is thought to be determined by their past experiences. However, few empirical studies have investigated whether this is true in diving animals. We recorded three-dimensional movements and mouth-opening events from three Antarctic fur seals during their foraging trips to examine how they adapt their behaviour based on past experience—continuing to search for prey in the same area or moving to search in a different place. Each dive cycle was divided into a transit phase and a feeding phase. The linear horizontal distance travelled after feeding phases in each dive was affected by the mouth-opening rate during the previous 244 s, which typically covered two to three dive cycles. The linear distance travelled tended to be shorter when the mouth-opening rate in the previous 244 s was higher, i.e. seals tended to stay in the same areas with high prey-encounter rates. These results indicate that Antarctic fur seals follow decision-making strategies based on the past foraging experience over time periods longer than the immediately preceding dive.

31 Background: PD-1 (Programmed Death 1), a member of the B7-CD28 family, is a cell surface coinhibitory receptor expressed on T cells, B cells, monocytes, and natural killer T cells, following activation. Recently, PD-1 expression is involved with malignancy have been reported in cancer cells and virus-infected cells. The aim of this study is to clarify the impact of PD-1 expression on long term outcome of gastric cancer. Methods: Total of 105 patients who were performed gastrectomy in Stage 2/3 gastric cancer. For resected specimen was performed immunostaining of PD-1. We counted PD-1 positive T cells in the tumor across five adjoining high power fields (×400 magnification level). And, we calculated the percentage of the total cell number, it was considered PD-1 positive more than 40%. We investigated clinicopathological factors and survival. Results: 28 cases were PD-1 positive expression. There was no significant difference between the two groups in the clinicopathological factors (age, gender, tumor size, differentiation, depth of invasion, lymph node metastasis, stage, lymphatic invasion and venous invasion). There was no difference in overall survival rate at 3 years (PD-1 positive vs. negative 76% vs. 81%, p=0.552). PD-1 positive expression was significantly poorer in disease-free survival rate (36% vs. 65%, p=0.022). 10 cases were Foxp3 positive expression, and Foxp3 positive expression was related with PD-1 expression. Conclusions: The PD-1 expression in the tumor could be a potential prognostic factor in gastric cancer.

620 Background: Oxaliplatin(Ox) based regimen is widely used in colorectal cancer patients.One of the major adverse effects of Ox is a neuropathy. There is no useful biomarker predicting such adverse effect. The aim of this study is to evaluate platinum concentration as a biomarker predicting the adverse effect. Methods: Ten patients who underwent curative colectomy were included in this study. Final stage of all patients was UICC stage III. All patients underwent adjuvant chemotherapy by CapeOX regimen for eight cycles (or six months). Blood samples were collected after fourth cycle and last cycle. Ox concentration was measured in red blood cells (RBC) and serum, and evaluated the kinetics of platinum (PL) in blood. In addition, we investigated relationship between Ox concentration and adverse effects. Results: 1) Kinetics of PL concentration: PL concentration in RBC tended to be correlated with the difference of RBC numbers between pre- and post-chemotherapy (R2=0.358, p=0.068). The PL concentration in RBC siginificantly correlated with the difference of mean corpuscular volume (MCV) between pre- and post-chemotherapy (R2=0.661, p=0.004). After four cycle, the platinum concentration in RBC siginificantly correlated with the hemoglobin and hematocrit (R2=0.447, p=0.004 and R2=0.425, p=0.041). There was no siginificant difference in PL concentration in both RBC and serum between the points after four cycle and last cycle points (RBC: 1380.5±495.2 ng/ml vs. 1107.0±699.2 ng/ml Aserum: 210.1±38.9 ng/ml vs. 221.2±99.2 ng/ml). 2) PL concentration and adverse effects: PL concentration did not elevate depending on cycle number. There was no siginificant correlations between PL concentrations in RBC or serum and the grade of neuropathy. Conclusions: The PL concentration was significantly related with the difference of RBC numbers and MCV between pre- and post-chemotherapy. However, there was no siginificant relationship between Ox concentration in blood and side effects including neuropathy. So Ox concentration in blood could not be a reliable biomarker for predicting the grade of neuropathy. Clinical trial information: 000009128.

Mediastinal parathyroid carcinoma is very rare regardless of whether it is functioning, and it is sometimes problematic in both diagnosis and treatment. We herein report a case of primary hyperparathyroidism (PHP) associated with large parathyroid carcinoma extending into the superior mediastinum successfully removed by a transcervical approach, with a review of recent literature. A 61-year-old male with a six-year history of PHP and urinary stone disease presented with an abnormal mediastinal mass in a chest X-ray. His serum level of intact parathyroid hormone (PTH) was markedly elevated to 1,220.0 pg/mL (normal range: 10.0-65.0 pg/mL), though calcium and phosphorus levels were within normal limits. Chest computed tomography demonstrated a large mass in the superior mediastinum, displacing the trachea to the right and reaching the aortic arch, posteriorly adjacent to the thoracic vertebra. Transcervical extirpation of the tumor was performed. The resected specimen measured 50x85x38 mm and weighed 56.8 g. Histopathological examination revealed a capsular invasion of the tumor cells, and a diagnosis of parathyroid carcinoma was made. On the 8th postoperative day, the patient was discharged uneventfully with a decreased serum level of PTH (59.0 pg/mL), and no recurrent disease or exacerbation of hyperthyroidism was observed 36 months after surgery.

Pleural metastasis of synovial sarcoma that originally developed in the soft tissue is a very rare entity. We report here the detailed clinical features of such a case. An asymptomatic 25-year-old female, with a history of a resected synovial sarcoma in her left brachial muscle and pulmonary metastasectomy of the right lung, presented a small nodule in the periphery of the left lung on a routine chest-computed tomography. Exploratory thoracoscopy was then performed. A soft flat red tumor approximately 2 cm in diameter was shown on the pleura of the lingula, mimicking a blood clot on the pleura. The tumor was removed by partial resection of the lung. The mass lay in the pleura and did not seem to invade the lung parenchyma macroscopically. Intraoperative frozen sectioning evidenced metastatic synovial sarcoma. Many small patchy red lesions were also found on the visceral pleura of the lung and parietal pleura of the diaphragm. We diagnosed unresectable pleural metastases of synovial sarcoma and finished the operation after sampling another pulmonary pleural lesion. The patient then underwent ifomide-based chemotherapy and survived for 3 years after her initial surgery. Postoperative histopathological examination revealed a solid and bundle-like proliferation of a short spindle cell tumor with a monophasic pattern, which was diagnosed as a metastatic pleural synovial sarcoma. A hemangio-pericytomatous pattern was also seen; therefore the lesion looked like a blood clot because of its rich vascularity.

A 74-year-old asymptomatic female presented with an anterior mediastinal mass incidentally discovered on a routine chest X-ray. Systemic evaluation demonstrated no metastatic lesions. The patient underwent an extended thymectomy via median sternotomy on suspicion of a thymoma. The tumor had arisen from the left half of the thymus without a pedicle and had directly invaded into the left lung and pericardium. The tumor was resected with the entire thymic tissue, and the invaded lung and pericardium were resected en-bloc. The size of the tumor was 5.3x4.0 cm. A disseminated lesion on the mediastinal pleura was also resected. Histopathologically, the lesion mainly consisted of non-atypical spindle-shaped tumor cells in a so-called "patternless pattern" with various densities of collagenous background. Pleomorphism and mitoses were not significant. Immunohistochemical analysis revealed mesenchymal positive markers such as vimentin and CD34. Epithelial markers such as CAM 5.2 and AE1/AE3 were negative. S-100 protein and desmin were not stained. Solitary fibrous tumor of the thymus was diagnosed histologically. Postoperative adjuvant chemotherapy or radiotherapy was not undertaken because the benefits were uncertain. She is well without recurrence 3 months after the operation.

Objective: Impacts of mediastinal lymph node dissection on a patient’s course after pulmonary resection is unclear in octogenarians with non-small cell lung cancer. Methods: Retrospectively identified subjects included 39 octogenarians and 1 nonagenarian, with grades according to the Charlson Comorbidity Index ranging from only 0 to 2. We performed mediastinal lymph node dissection in 19 patients (D group), and just lymph node sampling biopsy in the other 21 (S group). We compared clinicopathologic features and outcome after surgery between both groups. Results: Deterioration of performance status at the time of discharge, evident in 17 patients overall, was significantly more frequent in the D group. Postoperative complications occurred in 27 patients overall and there was no significant difference between the two groups. Survival rates in younger patients at 1, 3, and 5 years were 86, 59, and 49%, respectively; in octogenarians these were 83, 58, and 42% (no significant difference). Nor did survival differ significantly by surgical management of mediastinal lymph nodes; 1-, 3-, and 5-year survival rates were 94, 63, and 40%, respectively in the D group and 78, 66, and 43%, respectively in the S group. Conclusion: Octogenarians with non-small cell lung cancer should be treated by urgent pulmonary resection whenever possible. Since mediastinal lymph node dissection has little effect on long-term survival or the carried risk of worsening performance status at discharge, pulmonary resection without complete mediastinal lymph node dissection should be considered.

To prevent various distresses after proximal gastrectomy, reconstruction by interposed jejunal pouch has been advocated as an organ-preserving surgical strategy to ensure favorable quality of life for the patients.Proximal gastrectomy was performed in 9 patients with gastric cancer in the upper third of the stomach. Four patients were randomly selected for reconstruction by jejunal pouch interposition (JPI group), while 5 had reconstruction by jejunal interposition (JI group). The patients who underwent JPI and JI were followed up to evaluate resumption of normal diet, change in body weight, and clinical symptoms.The JPI group showed a significant dietary advantage. Three months after surgery, JPI patients could eat more than 80% of the volume of their preoperative meals, whereas JI patients ate less than 50%. The percentage of postoperative body weight loss was higher in the JI group than in the JPI group because the volume of the remnant stomach was more adequate in the latter. Moreover, it was easier to enter the remnant stomach and duodenum for endoscopic fiberscopy in the JPI group for the treatment of hepato-biliary pancreatic disease.JPI is an effective method for preservation of gastric function after proximal gastrectomy.

A 63-year-old man presented with dyspnea on effort. Chest computed tomography showed an anterior mediastinal mass and a lung mass in the right lower lobe. Thallium scintigraphy revealed accumulation in the mediastinal mass. Therefore, under diagnosis of invasive thymoma or thymic carcinoma associated with suspected lung cancer, exploratory right thoracotomy was undertaken through a median sternotomy with video-assisted thoracoscopic support. The lung mass was intraoperatively diagnosed as squamous cell carcinoma. Right lower lobectomy and total thymectomy were then carried out without additional incision. Thymic small cell carcinoma was diagnosed; therefore the patient received 50 Gy of irradiation to the mediastinum. Ten months after surgery the patient is alive without recurrence.

Stiff-person syndrome (SPS) is a rare autoimmune neurologic disorder characterized by painful tonic spasms in systemic skeletal muscles. 1 Anti-glutaminic acid decarboxylase (GAD) antibodies are produced with disturbing synthesis of -aminobutylic acid, one of the important suppressive neurotransmitters in the central nervous system. In some patients SPS is reportedly accompanied by thymomas, 2-4 and in these patients surgical resection of the malignancy reportedly reduces the neurologic symptoms of SPS. We report herein the clinical course of a patient with SPS associated with invasive thymoma.

We herein report a case of gastrointestinal bleeding induced by angiodysplasia of the cecum in a case of Bernard-Soulier syndrome with recurrent breast cancer. In spite of endoscopic hemostatic therapy and interventional embolization, she had repeated massive bleeding from the cecal lesion. In addition, she had chronic hepatitis C and progressive liver tumors metastasized from breast cancer, and she finally died of hepatic failure. There are four case reports in the literature describing Bernard-Soulier syndrome with gastrointestinal bleeding angiodysplasia. The reported cases benefited from hormonal, endoscopical hemostasis and surgical therapy. In our case, because of her terminal metastatic breast cancer, only conservative treatments were administered after the third bleed. Both the endoscopic hemostatic method and interventional embolization showed only a temporary effect. Surgical treatment should be considered if the general condition can tolerate a surgical procedure.

We report a case of perforation, fistula formation, and small bowel obstruction in a 2-year-old child who had ingested 32 small magnets. Multiple magnets will attract one another through the bowel wall and lead to pressure necrosis with complications. We recommend early surgical intervention before the onset of gastrointestinal complications if ingested multiple magnets have not moved on the follow-up radiograph. Both clinicians and the lay population need to be aware that multiple magnets can be hazardous foreign bodies for children.

Purpose: Identification of cancer/testis antigens useful for diagnosis or immunotherapy of cancers was attempted by cDNA expression cloning with patients' sera (SEREX). Experimental Design: cDNA expression libraries made from testis or endometrial cancer cell lines were screened using sera from patients with endometrial cancer or melanoma patients immunized with dendritic cells pulsed with autologous tum or lysates. Tissue-specific expression by RT-PCR and immunogenicity by Western blotting of the bacterial recombinant antigen with sera from cancer patients were evaluated. Results: A cancer/testis antigen, CAGE, was isolated by two independently performed SEREX. CAGE was expressed in various cancer cell lines including endometrial cancer, colon cancer, and melanoma in 7 of 10 endometrial cancer tissues and in 1 of 3 atypical endometrial hyperplasia, but not in normal tissues including the endometrium and testis. The protein expression on cancer cells was confirmed by Western blot analysis with the recombinant CAGE protein, anti-CAGE IgG antibody was detected in sera from 5 of 45 endometrial cancer, 2 of 24 melanoma, and 2 of 33 colon cancer patients, but not in sera from healthy individuals. By ELISA analysis, anti-CAGE antibody was detected in 12 of 45 endometrial cancer, 2 of 20 melanoma, and 4 of 33 colon cancer patients. Intriguingly, anti-CAGE antibody was highly positive in 7 of the 13 (53.8%) microsatellite instability (MSI)-H patients with endometrial cancer, but negative in 20 non–MSI-H patients (P = 0.001). Conclusion: CAGE may be useful for immunotherapy and diagnosis of various cancers particularly MSI-positive endometrial cancer.

Preoperative right portal vein embolization enhances remnant liver function following massive hepatectomy. Several studies have reported an increase in the volume of the left hepatic lobe after right portal vein embolization, but little information exists regarding heat shock protein induction in hepatocytes after right portal vein embolization. The objective of this study is to determine whether heat shock protein is induced in hepatocytes after right portal vein embolization in patients who underwent extended right hepatic lobectomy.Four patients with gallbladder cancer and one patient with intrahepatic cholangiocellular carcinoma who underwent extended right hepatic lobectomy combined with caudate lobectomy and resection of the extrahepatic bile duct after right portal vein embolization were enrolled in this study. Operation was performed 21-36 days after right portal vein embolization. At operation, small liver specimens were taken immediately after laparotomy from both the right anterior segment (embolized lobe) and lower part of the left medial segment (non-embolized lobe) and heat shock protein 70 was induction in these specimens was measured by Western blotting.Heat shock protein 70 was induced in the left lobe relative to the right lobe in four patients, three of whom had an uneventful postoperative course.This paper is the first report to show the induction of heat shock protein 70 in the non-embolized hepatic lobe after right portal vein embolization in the clinical cases.

Carcinogenesis of cervical cancer has been investigated, and p16(INK4a) overexpression in squamous cell carcinoma of the cervix has been reported as a result of infection by human papillomavirus (HPV) (eg, HPV 16), and the consequence of the retinoblastoma (Rb) protein inactivation by HPV E7 protein. However, to our knowledge, there have been no studies on the relation between p16(INK4a) overexpression associated with HPV and small cell carcinoma of the cervix, which behaves more aggressively clinically than squamous cell carcinoma. The purpose of this study was to determine whether p16(INK4a) is overexpressed in small cell carcinoma, and if p16(INK4a) is overexpressed, the types of HPV that are related to this cancer. We reviewed 10 cases of small cell carcinoma and examined them for p16(INK4a) overexpression by immunohistochemistry. We also performed HPV typing with polymerase chain reaction (PCR)-sequencing analysis and in situ hybridization and found that p16(INK4a) was overexpressed in every case. PCR-sequencing analyses revealed that all cases were HPV-positive and that 9 cases were positive for HPV 18. Five of the 9 cases positive for HPV 18 were also positive by in situ hybridization and yielded a punctate signal, considered to represent the integrated form. In conclusion, p16(INK4a) was overexpressed and HPV 18 was frequently detected in an integrated form in small cell carcinoma. Therefore, inactivation of Rb protein by HPV 18 E7 protein may be associated with carcinogenesis of small cell carcinoma the same as inactivation of Rb protein by HPV 16 E7 protein is associated with carcinogenesis of squamous cell carcinoma.

A fluid-based Papanicolaou test has been established to improve sample collection and preparation. This study was the first large-scale investigation in Japan to examine the feasibility of using fluid-based Papanicolaou specimens to detect human papillomavirus (HPV) using Hybrid Capture II and polymerase chain reaction (PCR). Three thousand patients who visited Keio University Hospital between October 2000 and February 2001 were enrolled in the study. The results of the fluid-based Papanicolaou tests corresponded well with those of conventional Papanicolaou smears (96.8% concordance). The sensitivities of cervical neoplasia detection using the fluid-based Papanicolaou test (73.9%) and Hybrid Capture II (76.3%, P=0.55) were not significantly different. Among the cervical intraepithelial neoplasia 3 and squamous cell carcinoma specimens, HPV 16 and HPV 52 were predominantly detected using the PCR method. Although some DNA samples extracted from the fluid-based specimens were degradaded, PCR and direct sequencing could be performed without difficulty even after 1 year of specimen storage. We conclude that fluid-based Papanicolaou specimens can be applied to investigate HPV infection.

563 Background: Recent pharmacogenetic studies have revealed a significant association between uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms *28 and *6 and toxicities such as severe diarrhea and neutropenia under treatment with irinotecan. Moreover, the latter of these two polymorphisms is specifically detected in East Asian populations. We performed a prospective study to determine the optimal dose of this drug depending on which polymorphism is present in order to maximize the effectiveness of therapy while avoiding side effects. Methods: 59 patients from 11 institutions were enrolled in this study. Patients were assigned to one of the following three groups: wild type (*1/*1), heterozygous (*28/*1, *6/*1), or homozygous (*28/*28, *6/*6*, *28/*6*). The double heterozygous state (*28/*6) was included within the homozygous group. Second-line FOLFIRI was administered, with the dose of irinotecan at 150 mg/m2, in the wild type and heterozygous groups and at 100 mg/m2 in the homozygous group. The incidences of severe toxicities according to UGT1A1 gene type, response rate, and progression-free survival were investigated. Results: 26 (44.1%) were assigned to the wild type group, 28 (47.4%) to the heterozygous group, and 5 (8.5%) to the homozygous group. Grade 3 or higher severe toxicities were observed in 8 patients (30.8%) in the wild type group, 5 (17.9%) in the heterozygous group, and 1 (20.0%) in the homozygous group. No significant difference was observed among the three groups. The most frequently observed severe toxicities were neutropenia, nausea, vomiting, and diarrhea. The overall response rate (complete response + partial response) was 2 patients (7.7%) in the wild type group, 2 (7.1%) in the heterozygous group, and none (0.0%) in the homozygous group. Conclusions: In terms of tolerability and safety, the present results suggest that irinotecan should be administered at a dose of 150mg/m2 in heterozygous patients and 100 mg/m2 in homozygous patients receiving second-line FOLFIRI.

Although vaginal radical trachelectomy is an effective treatment for early stage cervical cancer and has an acceptable live birth rate, there are concerns over its oncological safety and possible surgical injury with this radical procedure. Moreover, most gynecologists have difficulty performing this unfamiliar procedure and require special training. Many of these problems can be overcome with the use of abdominal radical trachelectomy. The abdominal approach provides adequate resection of the parametrial and vaginal tissue and does not require special training. Only a few case studies have investigated abdominal radical trachelectomy. This retrospective study presents follow-up data and reviews a series of cases conducted in Japanese women with early stage cervical cancer who had undergone elective abdominal radical trachelectomy and pelvic lymphadenectomy between 2002 and 2008. The aim of the study was to assess the effectiveness and safety of the abdominal approach in this population. A total of 61 patients at a median age of 33 years (range, 26-44 years) were followed up for a median 27 months (range, 1-67 months). There were 6 recurrences (9.8%, 6/61); 1 occurred in a patient with adenocarcinoma. None of the other 5 recurrences were found in cases with a primary tumor diameter of

An 18-year-old woman presented with hemoptysis during long-distant running. A chest computed tomographic scan revealed a well-demarcated, round-shaped, solitary mass (3.0 cm in diameter) in the left pulmonary hilum. The bleeding was getting more often and a left upper lobectomy was carried out to avoid critical airway bleeding. A solid proliferation of short spindle cells with a remarkable whorl pattern was demonstrated histologically. Immunohistochemical studies showed positive for vimentin and S-100, and focally positive for epithelial membrane antigen. Primary pulmonary meningioma was thus diagnosed. The patient is well without recurrent disease 15 months after surgery.

The enhancing effect on liver metastasis produced by the excessive surgical stress of thoraco-laparotomy (TL), and its regulation with a radical scavenger, were studied in 10-week-old Donryu rats. The rats were divided into three groups: those given thoraco-laparotomy for 1 h (the TL group); those given laparotomy alone for 1 h (the L group); those given a short laparotomy (the C group). The effects of treatment with 5 mg/kg of EPC-K1 was assessed in the TL group. A rat hepatocellular carcinoma cell line AH 60C (5 x 10(5) cells) was administered into the portal vein under general anesthesia. The number of metastatic liver nodules was counted 3 weeks later, and the lipid peroxide (LPO) levels of the liver and serum were measured by the TBA method on postoperative days (PODs) 1, 2, and 3. The number of metastatic liver nodules was 40.6 +/- 29.7, 15.0 +/- 15.8, and 13.7 +/- 9.4 in the TL, L, and C groups, respectively. When EPC-K1 was administered to the TL group, the LPO level on POD 1 decreased from 49.8 +/- 25.8 to 18.9 +/- 7.9 nM/g, and the number of metastatic liver nodules decreased from 27.2 +/- 30.0 to 8.9 +/- 12.7 in parallel. The findings of this study suggested that the excessive surgical stress produced by thoraco-laparotomy enhanced liver metastasis in parallel with an increase in LPO levels; however, the radical scavenger EPC-K1 could aid in reversing this effect.

Vascular complications after the intravesical instillation of Bacillus Calmette-Guérin (BCG) therapy are extremely rare. We experienced a case of abdominal aortic aneurysmal infection excluded by a stent graft with an iliopsoas abscess after intravesical instillation of BCG therapy that required reoperation. Five years ago, an 81-year-old man was diagnosed with transitional cell carcinoma of the bladder. After transurethral resection of the bladder tumor and intravesical BCG therapy, a radical cystectomy was performed. Twenty-four months after intravesical BCG therapy, follow-up an abdominal computed tomographic (CT) scan revealed an aortic abdominal aneurysm. Endovascular aneurysm repair was performed, and the aneurysm was excluded postoperatively. Thirty months after the endovascular aneurysm repair (and 54 months after intravesical BCG therapy), a follow-up abdominal CT revealed a low-density area in the right iliopsoas muscle that formed a fistula to the excluded aneurysm. We performed CT-guided iliopsoas abscess drainage and collected yellow pus. Polymerase chain reaction analysis revealed that the pus was positive for Mycobacterium tuberculosis complex. The patient was diagnosed with abdominal aortic aneurysmal infection associated with iliopsoas abscess caused by Mycobacterium bovis, and surgery was performed. We performed an extra-anatomical bypass and removed the stent graft with debridement. When the aneurysmal wall was incised and resected, yellow pus surrounded the stent graft. In addition, a large fistula was present between the right posterolateral aortic aneurysmal wall and the iliopsoas abscess cavity. After the operation, the histopathological examination of excised abdominal aortic aneurysmal wall tissue revealed an epithelioid granuloma with caseous necrosis involving multinucleated giant cells, indicating M tuberculosis complex infection. Although the intravesical instillation of BCG therapy is considered safe, complications resulting from vascular infections can arise in extremely rare cases. The complication described in this case report emphasizes the need to cautiously select treatment for a mycotic aortic aneurysm after intravesical instillation of BCG therapy.

e14572 Background: Recent pharmacogenetic studies on irinotecan have revealed significant associations of UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms *28 and *6, the latter being specifically detected in East Asians resulting in severe toxicity such as severe diarrhea and neutropenia. It is necessary that the dose-finding trial that decided the optimal dose according to the gene polymorphism to draw out the maximum therapeutic effect while evading the side effect. Here, we present the final report of prospective trial of safety and efficacy about FOLFIRI ± bevacizumab (Bev) therapy according to each gene type of UGT1A1for Japanese patients with advanced CRC in second-line setting. Methods: Between September 2008 and March 2012, 59 patients were enrolled in this study. Grouping was defined as follows: wild group; both *28 and *6 were wild types, hetero group; *28 and either *6 was hetero type, and homo group; 28/*28 and *6/*6* or a both hetero types. In the 59 patients with advanced CRC treated with FOLFIRI ± Bev as a second line, wild and hetero groups were administered 150mg/m2 irinotecan, and homo group was 100mg/m2. The incidences of severe toxicities according to gene type of UGT1A1, the response rate and progression-free survival were investigated. Results: In the 59 patients, wild group was 28 (47%), hetero group was 26 (44.1%) and homo group was 5 (8.5%). 8 patients (29%) showed severe toxicities (grade 3 or more) in wild group, 5 patients (19%) in hetero group, 1 patient (20%) in homo group (P=0.71). Regarding the response rate, CR, PR, SD, PD was observed in 1 (4.0%), 1 (4.0%), 5 (20.0%) and 18 patients (72.0%), respectively in wild group, 0 (0.0%), 2 (8.3%), 5 (20.8%) and 17 patients (70.8%), in hetero group, 0 (0.0%), 0 (0.0%), 1 (20.0%) and 4 patients (80.0%), in homo group. The overall response rate (CR+PR) was 8.0% in wild group, 8.3% in hetero group, 0% in homo group (P=0.80). As for progression-free survival, the number of cycle to PD was 12.1 cycles (2-35 cycles) in wild group, 8.3 (2-20) in hetero group, 9.8 (6-14) in homo group (P=0.15). Conclusions: The dosages of 150mg/m2 irinotecan in hetero group, 100mg/m2 in homo group are safe and effective in FOLFIRI ± Bev therapy in the second line. Clinical trial information: UMIN000004773.

499 Background: Preoperative chemoradiotherapy (CRT) in rectal cancer reduces the local recurrence rate after operation and preserves the anus, but it is difficult to predict the effects of CRT. Multicenter randomized phase II clinical trial of preoperative chemoradiotherapy by S-1 vs UFT for rectal cancer was conducted to compare the toxicity and efficacy of CRT using oral DPD-inhibitory fluoropyrimidines (UFT versus S-1, (UMIN ID: 000001704)) in patients with locally advanced rectal cancer. Methods: In this randomized phase II study, during April 2008 to October 2010, rectal cancer patients (n=59) who underwent preoperative CRT were randomly divided into two groups; S-1 group (n=30, 80 mg/m2/day, 5 days/w x 4 w), and UFT (n=29, 300 mg/m2/day, 5 days/w x 4 w). Both groups were combined with 40Gy radiotherapy (2 Gy ×5 days/w × 4 weeks,total 40 Gy). The pathological response rate, clinical response rate by RECIST, and frequency of adverse events of CRT were compared between S-1 group and UFT group. Results: Response to CRT determined by histopathologic examination of surgically resected specimens and RECIST were as follows: responders (grade 2 or 3) were 60% (S-1) and 52% (UFT) (p=0.52). S-1 group showed 54% of response rate in pathological response, whereas UFT group showed 45% (p=0.43). In adverse events, frequence of Grade 2 and 3 diarrhea was significantly higher in S-1 group compared with UFT group. There was no difference between the two groups in compliance (S-1group: 83%, UFT group: 97%). Conclusions: Both S-1 and UFT were safely used for preoperative CRT. S-1 tended to show higher response rate than UFT, although diarrhea in S-1 was higher than in UFT. Clinical trial information: 000001704.

OBJECTIVE In cervical intraepithelial neoplasia (CIN), p16(INK4a) immunohistochemistry has been reported to be a useful diagnostic biomarker. However, limited information is available about the association between the p16(INK4a) immunohistochemistry and the outcomes of CIN. Here, we report p16(INK4a) immunohistochemistry as an effective biomarker to predict the outcomes of CIN. METHODS p16(INK4a) immunohistochemistry was performed in patients with CIN from January 2000 to August 2009. Among these patients, we have performed a retrospective analysis of the medical records to evaluate the outcome of CIN 1-2 and performed statistical analysis to determine the correlation between p16(INK4a) expression and the outcomes. We also performed HPV genotyping and analyzed the relation between the infecting human papillomavirus (HPV) genotype and the outcomes. RESULTS A total of 244 patients, including 82 with CIN 1, 60 with CIN 2, and 102 with CIN 3, were examined. The rate of p16(INK4a) overexpression increased with increasing CIN grade, 20.7% for CIN 1, 80.0% for CIN 2, and 89.2% for CIN 3, with significant differences between CIN 1 and CIN 2-3 group. In the 131 CIN 1-2 patients, the progression rate was significantly higher for the patients showing p16(INK4a) overexpression than for those not showing p16(INK4a) overexpression (p=0.005); the regression rate was also found to be significantly lower for the patients showing p16(INK4a) overexpression (p=0.003). High-risk HPV genotypes were detected in 73 patients (73.7%). Both progression and regression rates were not significantly different between the high-risk HPV-positive and HPV-negative groups (p=0.401 and p=0.381, respectively). CONCLUSION p16(INK4a) overexpression was correlated with the outcome of CIN 1-2, and p16(INK4a) is considered to be a superior biomarker for predicting the outcome of CIN 1-2 compared with HPV genotyping.

The usefulness of a heat sensitivity test which involved performing an ATP assay on endoscopic biopsy materials for predicting the clinical response to hyperthermia was investigated in esophageal cancer patients. Following in vitro heat treatment of FM3A tumor cells, the heat sensitivity detected by ATPA was significantly correlated with that in the colony-forming assay, and the percent inhibition of the ATP level in the tumor cells was correlated with in vivo tumor growth. The heat sensitivity of the biopsy materials evaluated by ATPA correlated well with that of the resected specimens in 18 esophageal cancer patients, while the clinical response to thermal therapy was well predicted by the heat sensitivity of the biopsy materials evaluated by ATPA in seven of the patients. These results indicate that the heat sensitivity test conducted by performing an ATPA on endoscopic biopsy materials could be a useful indicator for predicting the clinical response to thermal therapy.

31 Background: Epigenetic modification by HDAC (histone deacetylase) plays important roles in the development and progression of cancer. It has been reported that CD133 positive cancer stem cells were induced through the HDAC → HIF-1α (Hypoxia Inducible Factor-1α) pathway, and Thrombospondin1 (THBS1) is associated with tumor angiogenesis. The aim of this study is to evaluate relationship between the HDAC, CD133, THBS1 and prognosis in gastric cancer. Methods: 65 patients of gastric cancer were enrolled in this study. HDAC1, CD133 and THBS1 expressions were evaluated in immunohistochemical (IHC) staining of surgical specimens. Relationship between the expressions of HDAC1, CD133, THBS1 and clinicopathological factors was investigated. Results: HDAC1-positive patients were 52% and had significantly poor prognosis compared with negative patients. There were more frequent liver metastasis and lymphatic invasion in positive patients. CD133-positive patients were 23.1% and had significantly poor prognosis compared with negative patients. There were more frequent depth wall invasion, distant metastasis, peritoneal recurrence. THBS1-positive patients were 26% and had significantly better prognosis compared with negative patients. In THBS1 positive patients, there was less lymph node metastasis, positive peritoneal cytology in ascites, distant metastasis and lymphatic invasion. CD133 expression is positively correlated with HDAC1. THBS1 expression revealed negative correlation with HDAC1. The survival rate of HDAC1 (+) / CD133 (+) group was significantly poor prognosis compared to the other group (HDAC1 (+) / CD133 (-), HDAC1 (-) / CD133 (+), HDAC1 (-) / CD133 (-)). HDAC1 (-) / THBS1 (+) group revealed significantly higher survival rate compared to the other group (HDAC1 (-) / THBS1 (+), HDAC1 (+) / THBS1 (+), HDAC1 (+) / THBS1 (-)). Conclusions: It was suggested that HDAC1 promoted CD133, suppressed THBS1 in gastric cancer and their interaction were increased the degree of malignancy.

Positron acceleration in a shock wave in an electron-positron-ion plasma is studied with one-dimensional, fully kinetic, electromagnetic particle simulations, with particular attention paid to the effect of inhomogeneity of external magnetic field B0. First, acceleration to γ ∼ 104, where γ is the Lorentz factor, is demonstrated for a shock wave in a uniform B0 with the shock speed νsh close to c cos θ, where c is the speed of light and θ is the angle between B0 and the wave normal. The acceleration is not saturated till the end of the simulation run. Then, the effect of nonuniformity of B0 is investigated: Comparisons are made between the case in which the difference (νsh − c cos θ) at the shock front changes from negative to positive values as the shock wave propagates and the case with this relation reversed. The latter is found to create a greater number of high-energy particles than the former.

38 Background: The risk category of gastrointestinal stromal tumors (GIST) is usually determined by tumor size and mitotic count. Because of technical complexity and tumor heterogeneity in biopsy, accurate preoperative evaluation of malignant potential of GIST is very difficult. The aim of this study is to evaluate the utility of preoperative PET-CT examination for predicting the malignant potential of GIST. Methods: Ten patients with GIST who underwent preoperative PET-CT examination were enrolled. They were divided into two groups (low/intermediate-risk or high-risk) by risk category (tumor size, mitotic index). The relationships between the standardized uptake value (SUV) and GIST parameters including the size, mitotic index and Ki67 index were examined. Results: There was a significant correlation between the mitotic index and the SUV (p=0.029) but tumor size is not correlated with SUV. The SUV was significantly higher in the high-risk group (11.0 ± 3.04) than in the low/intermediate-risk group (2.1 ± 1.5). The Ki67 labeling index was also significantly higher in the high-risk group (8.63 ± 6.2) than in the low/intermediate-risk group (1.75 ± 0.52). There was a significant correlation between the Ki67 labeling index and the SUV (p=0.028). A mitotic index of 5/50 HPF was equivalent to an SUV of 4.3, and a Ki67 labeling index of 5 was equivalent to SUV of 6.3. SUV of 5 can predict the malignant potential between the high and low/intermediate risk. Conclusions: PET-CT can predict malignant potential. Cases with a high SUV, using a criterion of 5, might have malignant potential.

432 Background: Preoperative chemoradiotherapy (CRT) in rectal cancer reduces the local recurrence rate after operation and preserves the anus, but it is difficult to predict the effects of CRT. Our purpose of this study was to determine the effects and adverse events of CRT (S-1 or UFT) and to predict the response to CRT in rectal cancer by using both miRNA and DNA expression patterns. Methods: Rectal cancer patients (n=60) who underwent preoperative CRT were randomly divided into two groups (40Gy radiotherapy combined with S-1: 31 patients or UFT: 29 patients). The effects and adverse events of CRT were compared between S-1 group and UFT group. Additionally, RNA and DNA isolated from biopsy specimens of rectal cancer before preoperative CRT were hybridized to miRNA and DNA microarrays. Response to CRT was determined by histopathologic examination of surgically resected specimens. Results: Response to CRT determined by histopathologic examination of surgically resected specimens and RECIST were as follows: responders (grade 2 or 3) were 60%(S-1) and 52%(UFT) (p=0.52). Adverse events of CRT did not differ significantly between the 2 groups, and there was no adverse event of grade 3 or 4. As candidate predictive genes, 184 genes (S-1 group) and 193 genes (UFT group) were identified by DNA microarray, while 6 miRNA (S-1 group) and 16 miRNA (UFT group) were isolated by miRNA microarray as candidate predictive miRNA. Conclusions: Preoperative CRT using S-1 or UFT to rectal cancer is effective and the adverse events were acceptable. Expression profiling of both gene and miRNA may predict the effects of preoperative CRT, implicating the possible personalized therapy for patients with rectal cancer.

505 Background: Although Irinotecan prolongs survival, it causes severe diarrhea and neutropenia. Recent pharmacogenetic studies on irinotecan have revealed significant associations of UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms *28 and *6, the latter being specifically detected in East Asians resulting in severe toxicity. It is necessary that the dose-finding trial that decided the optimal dose according to the gene polymorphism to draw out the maximum therapeutic effect while evading the side effect. Previously, we showed UGT1A1 polymorphisms in Japanese patients (2011 ASCO-GI). Here, we present the interim report of prospective trial of the safety about FOLFIRI therapy according to each gene type of UGT1A1 for Japanese patients with advanced CRC. Methods: From 2008, 250 Japanese patients in TOKUSHIMA University were enrolled in this study. Homo group (*6/*6 and *28/*28 or a both hetero types), hetero group (It was *28 and either *6 was hetero type), and wild group (*28 and *6 were wild types) were defined. On the 30 patients with advanced CRC treated with FOLFIRI after standard chemotherapy, wild and homo groups were administered 150mg/m2 irinotecan, and homo group was 100mg/m2. The incidences of severe toxicities in each gene type of UGT1A1 and the response rate in FOLFIRI therapy were investigated. Results: In Japanese people, UGT1A1*6 polymorphisms were higher than *28 (*6 homo 3%, hetero 27% vs *28 homo 0.5%, hetero 13%). On the 30 patients with advanced CRC treated with FOLFIRI, the genotypes of UGT1A1*28 were homozygous in 1 (3%) and heterozygous in 6 (20%), *6 were homozygous in 0 and heterozygous in 8 (27%). In *6 heterozygous patients, severe toxicities (grade 3 or more) were found (38%). In *28 heterozygous patients, 1 patient (17%) showed severe toxicities. There was no decrease of irinotecan doses in each group. The number of course to PD was 7.6 (1-23). Regarding the response rate, PR, SD, PD was observed in 2 (7%), 6 (20%) and 18 patients (60%), respectively. Conclusions: In our interim report, the dosages of irinotecan based on UGT1A1 polymorphisms are safety in FOLFIRI therapy.

Objective The aim of this study was to investigate the risk and recurrence of early invasive adenocarcinoma of the cervix, and to determine whether non-radical methods of management could be performed. Methods The medical and histopathological records of 50 patients with early invasive adenocarcinoma of the cervix treated at Keio University Hospital between 1993 and 2005 were reviewed, and compared with the literature. Results The median follow-up period was 64.3 months. The depth of stromal invasion was ≤3 mm in 33 cases and >3 mm, but ≤5 mm in 17 cases. The horizontal spread was ≤7 mm in 25 cases and >7 mm in 25 cases. One of the 33 cases that had tumor volumes of ≤500 mm3, and three of the 17 cases with tumor volumes of >500 mm3 were positive for lymph node metastasis. When our data were combined with previously reported results, statistically significant differences were observed between the tumor volume and the frequency of pelvic lymph node metastasis/the rate of recurrence (p

BACKGROUND/AIMS: Chemo-radiation therapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients show poor response to adjuvant CRT. We thus investigated the usefulness of RAD51 expressions as a predictive maker of the CRT response. METHODOLOGY: Twenty three biopsied specimens among forty two patients who were suffered from lower rectal cancer were investigated. All patients received preoperative CRT consisting of TS-1, concurrent with 40 Gy of pelvic irradiation before having curative radical resection. The relationship between pathological responses of the tumors after therapy and expression of RAD51 was evaluated by immunostaining of biopsied and resected specimen, and evaluated the expression of RAD51 as a predictive factor of CRT. RESULTS: Positive expression of RAD51 was observed in 14 of 23 biopsied specimens (61%), and 24 of 42 patients (57.1%) in resected specimen. All RAD51 positive case which expressed in biopsied specimen expressed RAD51 positive in resected specimen. In biopsied specimen, RAD 51 positively expressed in 62.8% (10 of 14 cases) of SD, 44.4% (4 of 9 cases) of PR, and 0% (0 of 0 case) of CR, whereas in resected specimen, RAD 51 positively expressed in 68.2% (15 of 22 cases) of SD, and 42.2% (9 of 20 cases) of PR and CR. There is a tendency of reverse correlation between clinical response and expression of RAD51. Regarding the correlation between pathological response and RAD51 expression in biopsied specimen, positive expression of RAD51 was recognized in 90% (9 of 10 cases) of Grade 1, 50% (5 of 10 cases) of Grade 2, and 0% (0 of 3 cases) of Grade 3, and in resected specimen, positive expression of RAD51 was recognized in 75.0% (15 of 20 cases) of Grade 1, 47.1% (8 of 17 cases) of Grade 2 and 20.0% (1 of 5 cases) of Grade 3. A significant reverse correlation was recognized between RAD51 expression and pathological responses both in biopsied and resected specimen.CONCLUSIONS: RAD51 expression could be one of the most important predictive factors of preoperative CRT for advanced lower rectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5084. doi:10.1158/1538-7445.AM2011-5084