[A Case of Neoadjuvant Chemotherapy with Modified FOLFOXIRI plus Bevacizumab for Transverse Colon Cancer with Invasion of the Gastric Antrum].

A 66-year-old male diagnosed with transverse colon cancer was admitted to our hospital. Computed tomography, colonoscopy, and esophagogastroduodenoscopy revealed locally advanced cancer with invasion of the gastric antrum. We staged the disease as cT4a, cN2, cM0, Stage ⅢB, with wild-type RAS expression. We performed an ileostomy prior to administering chemotherapy. The patient received 4 courses of modified FOLFOXIRI plus bevacizumab and 2 courses of FOLFIRI. The size of the tumor noticeably decreased after chemotherapy. The patient experienced grade 3 neutropenia, anorexia, and oral mucositis during chemotherapy. We performed a right hemicolectomy(D3), partial gastrectomy and ileum resection after administering neoadjuvant chemotherapy. The pathological stage of the disease was ypT2, ypN0, ypM0, ypStageⅠ, and the effect of the chemotherapy was Grade 1b. After the resection, he received mFOLFOX6 and CapeOX for 3 months as adjuvant chemotherapy. He remained cancer-free for 1 year and 3 months after the surgery. This result suggests that preoperative modified FOLFOXIRI plus bevacizumab chemotherapy is a useful regimen for the treatment of locally advanced colon cancer.

Laparoscopic excision of a retroperitoneal completely isolated enteric duplication cyst in an adult male: A case report and review of literature.

INTRODUCTION: Duplication cysts are very rare congenital malformations in adults. They are lined by gastrointestinal mucosa, connect to the digestive tract, and share smooth muscular layers and a common blood supply. In rare cases, duplication cysts are completely isolated from the digestive tract and have a proper blood supply. Completely isolated duplication cysts in the retroperitoneum are unusual so it is hard to diagnose them without a surgical resection. PRESENTATION OF CASE: A 19-year-old male presented at our emergency department with sharp abdominal pain. Contrast-enhanced computed tomography detected a 5-cm multilocular cystic mass located in the retroperitoneum, caudal to the pancreatic body. The cystic mass was safely resected with laparoscopic surgery without any complication. The final pathological diagnosis was an epithelium-lined duplication cyst in the retroperitoneal space. There was no evidence of malignancy in the duplication cyst. Intracystic bleeding was assumed to be the cause of the abdominal pain. DISCUSSION: The most common differential diagnoses of retroperitoneal cystic masses are pseudocysts related to pancreatitis, cysts from surrounding structures, and neoplasms. In this case, the cystic mass was diagnosed as completely isolated duplication cyst after surgical resection. It is very rarely observed in adults, but it should be listed on differential diagnoses because it has some possibility of malignancy. CONCLUSION: A completely isolated duplication cyst is very rare but noteworthy because there is some possibility of malignancy, ulcerative bleeding, and perforation. A surgical resection is recommended for diagnostic treatment. Laparoscopic surgery is favorable for intraoperative inspection and it is minimally invasive.

[A Case of Colon Metastasis from Breast Cancer with Resection by Laparoscopic Surgery].

A 50-year-old woman underwent breast-conserving surgery and axillary lymph node dissection for left breast cancer in May 2003. She received chemotherapy and radiation for lymph node, lung, and brain metastases. In October 2015, because of abdominal pain and melena, she underwent colonoscopy for suspected sigmoid colon metastasis from breast cancer. We performed laparoscopic sigmoidectomy and diagnosed sigmoid colon metastasis from breast cancer after histopathological examination. Colon metastasis from breast cancer can occur, although it is very rare.

A bilateral thoracic approach for esophageal cancer in the prone position.

Esophagectomy in the prone position has recently been introduced as a less-invasive procedure for treating esophageal cancer. We herein present a case of esophageal squamous cell carcinoma (ESCC) treated with a bilateral thoracic approach in the prone position. The patient was a 69-year-old male diagnosed with middle thoracic ESCC. Computed tomography scans and fluorine-18-fluorodeoxyglucose revealed possible metastasis to the lymph nodes on the left dorsal side of the descending thoracic aorta (DTA). After preoperative chemotherapy, we dissected the lymph node metastasis on the left dorsal DTA using the left thoracic approach, following resection of the ESCC by a right thoracic approach in the same prone position. The postoperative course was uneventful, and the patient was discharged 23 days after surgery. A bilateral thoracic approach for esophageal cancer in the prone position may be a new option for surgically treating esophageal cancer.

Radon inhalation protects against transient global cerebral ischemic injury in gerbils.

Although brain disorders are not the main indication for radon therapy, our previous study suggested that radon inhalation therapy might mitigate brain disorders. In this study, we assessed whether radon inhalation protects against transient global cerebral ischemic injury in gerbils. Gerbils were treated with inhaled radon at a concentration of 2,000 Bq/m(3) for 24 h. After radon inhalation, transient global cerebral ischemia was induced by bilateral occlusion of the common carotid artery. Results showed that transient global cerebral ischemia induced neuronal damage in hippocampal CA1, and the number of damaged neurons was significantly increased compared with control. However, radon treatment inhibited ischemic damage. Superoxide dismutase (SOD) activity in the radon-treated gerbil brain was significantly higher than that in sham-operated gerbils. These findings suggested that radon inhalation activates antioxidative function, especially SOD, thereby inhibiting transient global cerebral ischemic injury in gerbils.

Relapse-associated microRNA in gastric cancer patients after S-1 adjuvant chemotherapy.

S-1 has been recommended as adjuvant chemotherapy in patients after curative surgery for gastric cancer. However, some patients suffer recurrence even after S-1 adjuvant chemotherapy. The present study was conducted to find a predictive marker of the efficacy of S-1 adjuvant chemotherapy. We examined the microRNA (miRNA) expression of 35 patients who underwent S-1 adjuvant chemotherapy after curative surgery (R0) for pathological stage II or III gastric cancer. miRNAs were extracted from formalin-fixed, paraffin-embedded specimens for analysis and miRNA expression was examined using miRNA oligo chips. Fifteen patients relapsed and 20 did not over 5 years. Five miRNAs (miR-92b, 422a, 4732-5p, 4758-3p and 221) were highly expressed according to the tumor/normal (T/N) ratio in the patients who relapsed but not in those who did not relapse (P-value <0.05) by microarray analysis. If tumors showed high expression of 4 miRNAs (miR-92b, 422a, 4732-5p and 4758-3p) their positive predictive value of relapse was 93.8% and negative predictive value was 92.3%. In this case, their disease-free survival rate and overall survival rate were very poor. Our findings indicate that miR-92b, miR­422a, miR-4732-5p and miR-4758-3p are closely associated with relapse following S-1 adjuvant chemotherapy in gastric cancer.

Studies on possibility for alleviation of lifestyle diseases by low-dose irradiation or radon inhalation.

Our previous studies showed the possibility that activation of the antioxidative function alleviates various oxidative damages, which are related to lifestyle diseases. Results showed that, low-dose X-ray irradiation activated superoxide dismutase and inhibits oedema following ischaemia-reperfusion. To alleviate ischaemia-reperfusion injury with transplantation, the changes of the antioxidative function in liver graft using low-dose X-ray irradiation immediately after exenteration were examined. Results showed that liver grafts activate the antioxidative function as a result of irradiation. In addition, radon inhalation enhances the antioxidative function in some organs, and alleviates alcohol-induced oxidative damage of mouse liver. Moreover, in order to determine the most effective condition of radon inhalation, mice inhaled radon before or after carbon tetrachloride (CCl(4)) administration. Results showed that radon inhalation alleviates CCl(4)-induced hepatopathy, especially prior inhalation. It is highly possible that adequate activation of antioxidative functions induced by low-dose irradiation can contribute to preventing or reducing oxidative damages, which are related to lifestyle diseases.

[A case of high CEA colon cancer responding to neoadjuvant chemotherapy with FOLFIRI].

We report a case of high CEA advanced colon cancer, which we were able to down stage after treatment with FOLFIRI-1. The patient was a 56-year-old woman who had advanced sigmoid colon cancer with high CEA. It was suspected that the tumor had directly invaded the ovary by CT scan. For curative operation, hysterectomy was considered necessary. Neoadjuvant therapy was performed to avoid an extensive operation. After the fourth course, according to colonoscopy and CT findings, a significant tumor reduction was obtained. Sigmoid colorectomy with D3 nodal dissection was then performed. The histological diagnosis was pT1, pN0, PStage I. The histological effect was observed in lymph node metastasis. The patient was recurrence free at her 3-year follow-up examination.

[Advanced gastric cancer in an elderly woman showing histopathologic CR after a course of S-1 and CDDP combination therapy].

An 80-year-old woman was diagnosed with advanced gastric cancer of T2N0H0P0M0, Stage IB. She was strongly advised to undergo surgery, but refused this option. Because the performance status (PS)was 1, combination chemotherapy with S1 100 mg/day (day 1-21) and CDDP 50 mg/m2 (day 8) was initiated. After one course of treatment was completed, she changed her mind and expressed the wish to undergo an operation for her disease, which led to proximal gastrectomy (double tract reconstruction) being performed. A histopathological examination revealed CR of the disease with no cancer cells. As the population grows older, the number of elderly patients with advanced gastric cancer will increase in the future. Therefore, S-1 and CDDP combination therapy may be a treatment of choice for gastric cancer with dose reduction according to patient status, if the elderly patient refuses a curative operation. It may well prove to be an effective treatment in the elderly provided the dosage and administration are appropriate.

Applicability and performance of an imaging plate at subzero temperatures.

The performance of imaging plates (IPs) has not been studied at temperatures lower than 0 degrees C. In the present study, an IP was irradiated with gamma rays emitted from the mineral monazite at temperatures between -80 and 30 degrees C to determine its fundamental properties. The IP response as a function of irradiation time was found to be linear, suggesting that the IP works properly at low temperatures. Fading, an effect which should be considered at temperatures of more than 0 degrees C, was not observed at -30 and -80 degrees C. Furthermore, the fading-corrected PSL value of the IP irradiated at -80 degrees C was lower than at other temperatures (30, 5 and -30 degrees C). This can be explained by thermostimulated luminescence (TSL). Since the only intensive TSL peak in the temperature range from -80 to 30 degrees C is present at about -43 degrees C, some of the electrons trapped at F centers recombine with holes through the process of TSL before the stored radiation image is read out at room temperature. This finding suggests that the apparent sensitivity of the IP is lower at -80 degrees C although it is similar to sensitivities between -30 and 30 degrees C. This low sensitivity should be corrected to perform quantitative measurements.

First model of the effect of grain size on radon emanation.

The present model represents an improvement on previous models of radon emanation from soil by incorporating soil grain size in addition to moisture. Monte Carlo simulation was employed in the calculation since it was difficult to mathematically express the radon emanation fraction for the present soil model. Grain size is one of the most important factors in describing the properties of soil. Grain size was demonstrated to affect the radon emanation fraction, depending on moisture content. Although the emanation fraction is generally considered to be proportional to grain size, the result of the model calculation suggested that the effect of grain size is not so simple. This study should serve as an initial step toward improving the modeling of this radon emanation.

Differences of natural radioactivity and radon emanation fraction among constituent minerals of rock or soil.

We examined differences in the radioactive characteristics among the main minerals forming granite materials. Using a non-toxic high-density agent, minerals were separated from rock (granite-gneiss) and soil (weathered granite) samples. The natural radioactivity ((238)U and (226)Ra) and radon emanation fraction of the minerals were then studied by gamma-ray spectrometry. The radon emanation fractions (27-43%) of the minerals from the soil were much higher than those (0.6-4.6%) of the rock minerals. Additionally, the emanation fractions differed greatly among the minerals separated from both the bulk rock and soil. These results were discussed in terms of the differences of surface area and radium distribution in the mineral grains. It was noticeable that a higher emanation fraction than expected for quartz was commonly observed in the rock and soil samples. We then estimated the contribution of each constituent mineral to the total radon exhalation from the bulk samples. The result depended not only on the radon emanation fraction, but also on the (226)Ra activity and the mineral content. Furthermore, using the obtained data, we also discussed the effect of grain size on radon emanation and why this has been reported to vary markedly in previous studies.

[Successful resection of an advanced gastrointestinal stromal tumor by neoadjuvant chemotherapy with imatinib- a case report].

We report a case of a large gastric gastrointestinal stromal tumor (GIST), which we were able to curatively resect after treatment with a daily dosage of 400 mg imatinib for 3 months. The patient was a 46-year-old man whose chief complaint was anemia. Historical diagnosis by endoscopic biopsy was a c-kit-positive GIST of the stomach. From a CT scan, it was suspected that the tumor had directly invaded the pancreas. The tumor was 9 cm in size. For this case, total gastrectomy with distal pancreato splenectomy was necessary for curative resection. Imatinib mesilate was administered as neoadjuvant therapy according to the NCCN guidelines. After 3 months of treatment, CT revealed a dramatic reduction in tumor diameter of 61% and showed direct invasion of the pancreas. The radical operation was considered feasible and a partial gastrectomy was performed. The tumor did not invade other organs, and radical surgery was possible without rupture. The patient was recurrence free at his 12-month follow-up examination.

In vitro experimental study of the relationship between the apparent diffusion coefficient and changes in cellularity and cell morphology.

Diffusion-weighted magnetic resonance imaging (MRI) is frequently used clinically, and is available for the whole-body screening for tumors. The exact mechanism by which the apparent diffusion coefficient (ADC) value decreases in tumorous tissue remains unclear, although various theories have been proposed, including intracellular and extracellular factor theories. It is impossible to distinguish each factor in the intracellular and extracellular spaces as the source of MR signal generation by means of conventional comparison between MR images and pathological specimens. Other factors which have been reported to affect ADC include cellularity and cellular edema of human tissues, and temperature of phantoms at the time of measurement. We employed a new technique that enables cellular MR imaging using a newly developed bio-phantom containing a living culture tumor cell line, Jurkat-N1. We investigated possible reasons for observed decreases in ADC values for tumors, and we considered the contribution of both the intracellular and extracellular space to such a decrease. The ADC values of the bio-phantom increased with increasing heat exposure from 27 to 45 degrees C. ADC values also increased after the destruction by sonication of tumor cell membranes. ADC values decreased as cellularity increased in the bio-phantom. ADC values decreased due to cellular edema caused by a low salt concentration in the bio-phantom. Changes in pressure in the bio-phantom had no effect on the observed ADC values. We calculated both the intracellular ADC and extracellular ADC values using the ADC values, cellularity, and cellular volume of Jurkat-N1 cells in the bio-phantom. The extracellular ADC values in the bio-phantom were estimated to be lower than the ADC value of distilled water. These results indicate that not only intracellular ADC values, but also extracellular ADC values contribute to the determination of the ADC values of bio-phantoms. This is the first report to have examined the contribution of intracellular and extracellular space on the ADC values of bio-phantoms containing cultured tumor cells.

No Different Sensitivity in Terms of Whole-Body Irradiation between Normal and Acatalasemic Mice.

To elucidate the radiosensitivity of an acatalasemic mouse, we examined the time and dose-dependency in the survival rates, the lymphocytes and the intestinal epithelial cells, and the antioxidant function after 3.0 to 12.0 Gy whole body irradiation. Results showed that no significant differences between acatalasemic mice and normal mice were observed in the survival rates and the histological changes in spleens and small intestine after each irradiation. The catalase activities in livers and spleens of acatalasemic mice were significantly lower than those of normal mice and the glutathione peroxidase activity in livers of acatalasemic mice was significantly higher than that of normal mice. At 10 days after 6.0 Gy irradiation, the catalase activities in livers of acatalasemic and normal mice and that in spleens of normal mice significantly decreased compared with no-irradiation control, and there were no differences between those catalase activities. The total glutathione content in acatalasemic mice was significantly higher than that in normal mice at 10 days after 6.0 Gy irradiation. These findings suggested that the radiosensitivity of acatalasemic mice in terms of whole body irradiation doesn't significantly differ from that of normal mice, probably due to compensated sufficient contents of glutathione peroxidase and total glutathione in acatalasemic mice.

STAT1 activation-induced apoptosis of esophageal squamous cell carcinoma cells in vivo.

BACKGROUND: The induction of apoptosis might be a promising treatment for cancers refractory to conventional therapies, such as esophageal cancer. In this study, we examined whether epidermal growth factor-induced growth inhibition results from apoptosis of esophageal squamous cell carcinoma (SCC) cells as a result of STAT1 activation and evaluated whether interferon gamma (IFN-gamma) can induce apoptosis of cancer cells in vivo. METHODS: To assess the function of STAT1, we established stable transfectants expressing dominant-negative STAT1. Apoptosis was assessed by several experimental techniques, including flow cytometry. Differentiation was evaluated by Western blot test with involucrin used as a marker. In vivo, cancer cells were injected into male BALB/c nu/nu mice. Two weeks later, the mice started to receive injections of IFN-gamma or saline into a tail vein four times per week. Concentrations of IFN-gamma in the tumors were analyzed by enzyme-linked immunosorbent assay. Apoptosis was evaluated by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. RESULTS: Epidermal growth factor inhibited the growth of esophageal SCC cells by causing apoptosis through several pathways involving STAT1 activation. IFN-gamma induced the apoptosis of cancer cells, but it also promoted the differentiation (not apoptosis) of primary cultured cells derived from normal esophageal epithelium. IFN-gamma also inhibited the growth of xenograft tumors of esophageal SCC cells in vivo. CONCLUSIONS: Our results suggest that IFN-gamma is one candidate for cytokine-based therapy of cancer. IFN-gamma-induced STAT1 activation might be involved in the apoptosis of esophageal SCC cells and in the terminal differentiation of normal squamous cells. Further studies of STAT1 signaling pathways may provide the basis for new targeted therapeutic strategies for esophageal SCC.

[Measurement of the air kerma using dosimeters embedded in an acrylic phantom in interventional radiology.].

Interventional radiology procedure guidelines and a measurement manual (IVR guidelines) have been published for the maintenance of interventional equipment with an objective of avoiding serious radiation-induced skin injuries. In the IVR guidelines, the positioning of a dosimeter at the interventional reference point is determined, whereas placement of a phantom is not specified. Therefore, the phantom is placed at any convenient location between the dosimeter and image intensifier. The space around the dosimeter reduces detection of scattered radiation. In this study, dosimeters (consisting of a parallel plate ionization chamber, glass dosimeter and OSL dosimeter) were embedded in the phantom surface to detected scattered radiation accurately. As a result, when dosimeters were embedded in the phantom surface, the air kerma was increased compared with that when dosimeters were placed on the phantom. This suggested that embedded dosimeters were able to detect scattered radiation from the phantom.

Nicotine induces the fragile histidine triad methylation in human esophageal squamous epithelial cells.

The fragile histidine triad (FHIT) gene has been proposed to have an important role in very early carcinogenesis. Methylation of the FHIT gene is associated with transcriptional inactivation in esophageal squamous cell carcinoma, and FHIT inactivation has been linked to smoking-related carcinogenesis. In this study, we confirmed methylation of the FHIT gene in human esophageal squamous epithelial cells (HEECs) and examined whether nicotine induced alteration of FHIT. Methylation status in the promoter region of the FHIT gene and p16(INK4A) gene was determined by methylation-specific PCR in HEECs exposed to nicotine under various conditions. Methylation status of the FHIT gene was confirmed by DNA-sequencing analysis. Protein expression of Fhit and the DNA methyltransferases (DNMTs) DNMT1 and DNMT3a were assessed by immunoblot analysis. In the absence of nicotine, methylation of the FHIT gene and attenuation of Fhit protein were not detected in HEECs. Nicotine induced the methylation of FHIT gene and attenuated Fhit protein in association with increased expression of DNMT3a. Reexpression of Fhit protein in HEECs was found after cessation of moderate- to long-term exposure to nicotine. Our results show that nicotine induces methylation of the FHIT gene followed by loss of Fhit protein expression in HEECs. Continuous smoking may thus increase the risk of esophageal cancer.

Chenodeoxycholic acid stimulates the progression of human esophageal cancer cells: A possible mechanism of angiogenesis in patients with esophageal cancer.

Bile acids are known to promote the growth of gastrointestinal cancer. However, the underlying mechanism remains unclear. We examined whether bile acids induce tumor growth via the cyclooxygenase (COX)-2 angiogenic pathway. In vitro, esophageal squamous cell carcinoma (ESCC) cells and esophageal adenocarcinoma cells were studied. Production of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) in response to treatment with chenodeoxycholic acid (CDCA) was assessed by enzyme-linked immunosorbent assay (ELISA). COX-2 protein and VEGF protein were measured by immunoblot analysis, and COX-2 activity was measured by ELISA. In vivo, CDCA was administered to ESCC cell-bearing mice. Tumor tissues were analyzed immunohistochemically, and microvessel density was evaluated. Clinically, 134 patients with ESCC who underwent esophagectomy were studied. In vitro, CDCA induced the production of PGE2 and VEGF in dose- and time-dependent manners, and these effects were attenuated by a selective COX-2 inhibitor, mitogen-activated protein kinases inhibitor, or epidermal growth factor receptor inhibitor. CDCA-induced COX-2 in the cell lysate increased the secretion of VEGF into the culture medium. In vivo, CDCA markedly enhanced tumor growth and increased vascularization. Clinically, patients whose tumors expressed both COX-2 and VEGF had poor outcomes. Our results suggest that bile acids, important constituents of duodenal fluid, stimulate the development of human esophageal cancer by promoting angiogenesis via the COX-2 pathway.

A new specific gene expression in squamous cell carcinoma of the esophagus detected using representational difference analysis and cDNA microarray.

OBJECTIVES: To detect new specific gene expressions in squamous cell carcinoma of the esophagus. METHODS: Representational difference analysis of cDNA (cDNA RDA) was applied to a human esophageal cancer cell line (KYSE170) and a human esophageal epithelial cell line (HEEC-1). RESULTS: LAGE-1 was expressed specifically in KYSE170, but not in HEEC-1. It is also expressed in 27% of esophageal cancer cell lines (3/11) and 33% of esophageal cancer tissues (10/30), but not in other HEECs, normal esophageal epithelium, or other normal tissues except testis, ovary and kidney. The expression of LAGE-1 is strongly correlated with that of MAGE-A1 (p = 0.013, Fisher's exact probability test). Fibronectin, cytokeratin 6B, cytokeratin 19, cyclin D2 and Ten-m2 were detected as candidates for downregulated genes. Reduced expression profiles of them were also identified using cDNA microarrays. The expression of LAGE-1 was induced by 5'-aza-2'-deoxycytidine (5Aza-dC) and trichostatin A (TSA) in esophageal cancer cell lines, which did not express LAGE-1. In HEECs, 5Aza-dC induced LAGE-1 expression, but TSA did not. CONCLUSIONS: LAGE-1 expression was detected in esophageal cancer by cDNA RDA. LAGE-1 might have the potential to be a target antigen for anti-tumoral immunotherapy in esophageal cancers because of its tumor-specific expression similar to that of MAGE-A1.