[Laparoscopic Proximal Gastrectomy with Supra-Pancreatic Dissection First Approach].

BACKGROUND: In laparoscopic proximal gastrectomy(LPG)with esophago-gastro anastomosis, the key of obtaining good surgical view is how to exclude the stomach from the supra-pancreatic area. METHODS: We could get good surgical view at the supra-pancreatic area with gastro-ptosis by firstly dissecting lesser curvature. Followed by the supra-pancreatic dissection we could efficiently dissect the gastro-splenic ligament from cranial side. We performed this procedure in 20 cases with upper gastric cancer. We evaluate the surgical outcomes of this procedure(S group)comparing to that of the previous procedure in 14 cases(G group). RESULTS: The median operative time in S group was significantly shorter than that in G group (226 min vs 249 min, p=0.02). Other data were similar in 2 groups. CONCLUSIONS: The short-term clinical outcomes of LPG with supra-pancreatic dissection first approach revealed that this technique is safe and feasible.

Survival Benefit of Neoadjuvant Chemotherapy with S-1 Plus Docetaxel for Locally Advanced Gastric Cancer: A Propensity Score-Matched Analysis.

BACKGROUND: Postoperative docetaxel plus S-1 (DS) chemotherapy is expected to be the standard therapeutic strategy for pStage III gastric cancer based on the results of the JACCRO GC-07 study. Neoadjuvant chemotherapy (NAC) is thought to have several advantages over adjuvant settings. OBJECTIVE: This study aimed to compare the efficacies of NAC DS and the surgery-first strategy for advanced gastric cancer patients with D2 gastrectomy. METHODS: This was a retrospective, single-institution observational study. Of 171 patients with locally advanced (cStage IIB or III) gastric cancer who underwent curative D2 gastrectomy and received NAC DS and/or S-1 adjuvant chemotherapy between 2011 and 2017, 76 (after propensity score matching for 132 patients who met the eligibility criteria) were enrolled in this study. The 3-year progression-free survival (PFS) rate was used to directly compare efficacies between NAC DS patients and surgery-first patients. RESULTS: The 3-year PFS rates for the NAC DS group were significantly higher than those for the surgery-first group (80.0 vs. 58.7; p = 0.037), and the progression hazard ratio of the NAC DS group compared with the surgery-first group was 0.394 (95% confidence interval 0.159-0.978; p = 0.045). CONCLUSIONS: The NAC DS group showed a high 3-year PFS compared with the surgery-first group, with standard S-1 postoperative chemotherapy or observation. NAC DS can be expected to be beneficial as the standard therapy for advanced gastric cancer and should be adopted for the test arm of a randomized controlled phase III trial.

Antitumor effects of metformin are a result of inhibiting nuclear factor kappa B nuclear translocation in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is an intractable digestive organ cancer that has proven difficult to treat despite multidisciplinary therapy, and a new treatment strategy is demanded. Metformin is used for type 2 diabetes mellitus and its antitumor effects have been reported recently. Metformin exerts antitumor effects in various respects, such as inhibiting inflammation, tumor growth and epithelial-mesenchymal transition (EMT). However, few reports have described the efficacy of metformin on ESCC, and their findings have been controversial. We analyzed the antitumor effects of metformin and clarified its effects on anti-inflammation, growth suppression and EMT inhibition. Activation of nuclear factor kappa B (NF-κB), the major transcription factor induced by inflammation, was investigated by immunostaining. We found that localization of NF-κB in the nucleus was reduced after metformin treatment. This suggests that metformin inhibited the activation of NF-κB. Metformin inhibited tumor growth and induced apoptosis in ESCC cell lines. Associated with EMT, we examined cell motility by a wound healing assay and the epithelial marker E-cadherin expression of various ESCC cell lines by western blotting. Metformin inhibited cell motility and induced E-cadherin expression. In conclusion, metformin showed multiple antitumor effects such as growth suppression, invasion inhibition, and control of EMT by inhibiting NF-κB localization on ESCC. Further exploration of the marker of treatment efficacy and combination therapy could result in the possibility for novel treatment to use metformin on ESCC.

ZNF750 Expression Is a Potential Prognostic Biomarker in Esophageal Squamous Cell Carcinoma.

OBJECTIVE: ZNF750, a transcriptional regulator of epidermal differentiation, has been identified as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the clinical and prognostic significance of ZNF750 expression and to evaluate the effect of ZNF750 knockdown on cell proliferation, migration, and invasion in ESCC. METHODS: A total of 124 patients with ESCC who underwent curative esophagectomy were evaluated in this study. The expression of ZNF750 in surgical specimens was immunohistochemically assessed and used in the analysis of clinicopathological features and overall survival (OS). The molecular role of ZNF750 was investigated by ZNF750 knockdown using small interfering RNA (siRNA) in ESCC cell lines. RESULTS: Low ZNF750 expression had a significant correlation with positive lymph node metastasis (p = 0.028). Furthermore, there was a significant relationship between low expression of ZNF750 in ESCC and a poor OS, and a multivariate analysis showed that low ZNF750 expression was an independent prognostic factor (p = 0.020). The cell growth, migration, and invasion were significantly increased by downregulation of ZNF750. CONCLUSIONS: The low expression of ZNF750 was significantly associated with a poor prognosis, and ZNF750 expression may, therefore, be a reliable prognostic biomarker in ESCC.

Fra-1 Regulates the Expression of HMGA1, Which is Associated with a Poor Prognosis in Human Esophageal Squamous Cell Carcinoma.

BACKGROUND: The expression of Fos-related antigen 1 (Fra-1) affects tumor progression, migration, and invasion. In this study, we identified the genes regulated by Fra-1 in esophageal squamous cell carcinoma (ESCC). METHODS: We constructed Fra-1 knockdown models via the transfection of small interfering RNA (siRNA) into ESCC cell lines (TE10, TE11). The expression levels of the genes in the knockdown models were analyzed using a microarray and a Biobase Upstream Analysis, while the expression levels of the candidate genes in the primary tumors of surgical specimens obtained from ESCC patients were determined using real-time polymerase chain reaction (PCR) and immunohistochemical staining. The clinicopathological features were then analyzed. RESULTS: The Biobase Upstream Analysis showed the high-mobility-group protein-1 (HMGA1) to be a significant gene regulated by Fra-1. Actual binding of Fra-1 to the promotor region of HMGA1 was revealed in subsequent chromatin immunoprecipitation PCR experiments. Patients with a positive HMGA1 expression had a poor prognosis, and a multivariate analysis demonstrated a positive HMGA1 expression to be a significant independent prognostic factor. CONCLUSION: HMGA1 is regulated by Fra-1 in ESCC, and the HMGA1 expression is significantly associated with a poor prognosis in ESCC patients. Downregulation of the HMGA1 expression may become a practical treatment strategy against ESCC in the future.

ZNF750 Expression as a Novel Candidate Biomarker of Chemoradiosensitivity in Esophageal Squamous Cell Carcinoma.

OBJECTIVE: ZNF750, an epidermal differentiation regulator, has been suggested to act as a tumor suppressor of esophageal squamous cell carcinoma (ESCC). Although a correlation between the epidermal differentiation gene and resistance to chemoradiotherapy (CRT) has been posited, no data regarding the ZNF750 status in ESCC have been reported. The aim of the present study was to evaluate the relationship between ZNF750 expression and response to CRT in ESCC. METHODS: Eighty-seven patients who had been pathologically diagnosed with ESCC were evaluated in the present study. All patients underwent neoadjuvant CRT, followed by curative esophagectomy. The expression of ZNF750 in pretreatment biopsy samples was immunohistochemically investigated and compared to the histopathological effectiveness of CRT in surgical specimens. RESULTS: High expression of ZNF750 was closely correlated with good sensitivity to CRT (p = 0.016). A univariate analysis showed that high/intermediate expression of ZNF750 was a significant predictive factor for good sensitivity to CRT (p = 0.006). High/intermediate expression of ZNF750 (30% or more) remained an independent predictive factor for sensitivity to CRT in a multivariate analysis (p = 0.033). CONCLUSIONS: ZNF750 expression predicts sensitivity to CRT and can be a biomarker that reliably predicts the response of ESCC to CRT.

Drill needle aspiration biopsy for submucosal tumors in an experimental study.

BACKGROUND AND AIMS: EUS-guided FNA biopsy has been widely performed to aid in the diagnosis of submucosal tumors (SMTs). However, in cases of small tumors, the diagnostic yield of EUS-FNA is poor. Therefore, it is necessary to develop a new needle for the diagnosis. We developed a device with a new mechanism that we refer to as a drill needle aspiration biopsy (DNAB). The aim of this study was to evaluate the use of DNAB in resected gastric SMT specimens. METHODS: A drill needle with a sharp tip and wide ditch was inserted into a catheter for angiography. Continuous suction is enabled through the catheter at the tip. DNAB was performed with one pass and one stroke in 13 gastric SMTs resected by operation. Similarly, FNA was performed by one pass and ten strokes. These gastric tumors included nine diagnosed gastrointestinal stromal tumors and four undiagnosed SMTs by preoperative examinations. The tissue quantity between DNAB and FNA was macroscopically and microscopically examined. RESULTS: All 13 drill biopsy specimens were obtained. Additionally, all 13 gastric SMTs, including 4 undiagnosed tumors, could be diagnosed by DNAB. The quantity of each specimen obtained by DNAB was macroscopically and microscopically much greater than that by FNA. In particular, for tumors <25 mm in the longer axis, the ratio of microscopic diagnosable cases was 100 % (7/7) for DNAB and 42.9 % (3/7) for FNA. CONCLUSIONS: DNAB is a novel method that can obtain more tissue than FNA for small gastric SMT.

Gastric Resection Under Retroflexed Endoscopic Guidance: A Reliable Procedure for Totally Laparoscopic Subtotal Gastrectomy.

BACKGROUND/AIMS: Totally laparoscopic distal gastrectomy (TLDG) has become a feasible and safe surgical option for early gastric cancer. However, determining the transection line of the stomach without palpation is still difficult. This study aimed to assess the efficacy of TLDG for gastric resection under retroflexed endoscopic guidance (GRREG) in patients with gastric cancer in the middle third of the stomach. METHODS: Fifteen patients with gastric cancer underwent TLDG using GRREG. Preoperative tumor localization using endoscopic metal clips was performed in all cases. After lymphadenectomy, two-thirds of the estimated transection line was occluded by an endoscopic stapler, beginning at the lesser curvature. Under gastric occlusion, the gastroscope was passed via the narrow lumen along the greater curvature followed by retroflexion to reveal the occlusion line, marking clips, and tumor in the same field of view. This view verified the safe oncological transection line. RESULTS: All patients had cancer-free margins and did not require additional surgery. The mean (±SD) proximal margin was 23.5 ± 10.4 mm. There were no procedure-related complications. CONCLUSIONS: GRREG was a safe and effective technique for TLDG. Ideal transection of the stomach was achieved using a combination of an endoscopic stapler and gastroscope retroflexion.

Is "functional end-to-end anastomosis" really functional? A review of the literature on stapled anastomosis using linear staplers.

PURPOSES: Anastomosis is one of the basic skills of a gastrointestinal surgeon. Stapling devices are widely used because stapled anastomosis (SA) can shorten operation times. Antiperistaltic stapled side-to-side anastomosis (SSSA) using linear staplers is a popular SA technique that is often referred to as "functional end-to-end anastomosis (FEEA)." The term "FEEA" has spread without any definite validation of its "function." The aim of this review is to show the heterogeneity of SA and conventional hand-sewn end-to-end anastomosis (HEEA) and to advocate the renaming of "FEEA." METHODS: We conducted a narrative review of the literature on SSSA. We reviewed the literature on ileocolic and small intestinal anastomosis in colonic cancer, Crohn's disease and ileostomy closure due to the simplicity of the technique. RESULTS: The superiority of SSSA in comparison to HEEA has been demonstrated in previous clinical studies concerning gastrointestinal anastomosis. Additionally, experimental studies have shown the differences between the two anastomotic techniques on peristalsis and the intestinal bacteria at the anastomotic site. CONCLUSIONS: SSSA and HEEA affect the postoperative clinical outcome, electrophysiological peristalsis, and bacteriology in different manners; no current studies have shown the functional equality of SSSA and HEEA. However, the use of the terms "functional end-to-end anastomosis" and/or "FEEA" could cause confusion for surgeons and researchers and should therefore be avoided.

Experimental analyses of the cavitation generated by ultrasonically activated surgical devices.

PURPOSE: Recently, the incidence of postoperative pancreatic leakage has been reported to have significantly increased after laparoscopic gastrectomy for gastric cancers in comparison to open surgery. Although their lateral thermal spread has been shown to be smaller than that of other electrosurgical devices, ultrasonically activated surgical devices (USADs) have been suggested as one of the causes. We therefore hypothesized that cavitation generated by USADs could cause injuries to pancreatic tissue. Our retrospective study showed that the amylase activity in the drainage fluid of patients in whom surgery was performed using a USAD with a curved blade was significantly higher than that in patients in whom surgery was performed using a USAD with a straight blade. We therefore focused on the effects of straight and curved USAD blades. METHODS: The distribution of microbubbles generated in degassed water, which produce mechanical and biological tissue destructive forces, was measured and compared between the two types of USAD. RESULTS: More microbubbles were found to be generated from the side aspect of the curved blade, and the mechanical and biological destructive forces were found to be significantly higher than those generated by the side aspect of the straight blade. CONCLUSIONS: These findings strongly suggest that cavitation generated by USADs could injure pancreatic tissues in the clinical cases. Surgeons should be aware of these properties of devices to achieve safe and secure surgeries.

Synthetic polyglycomer short-term absorbable sutures vs. polydioxanone long-term absorbable sutures for preventing incisional hernia and wound dehiscence after abdominal wall closure: a comparative randomized study of patients treated for gastric or colon cancer.

PURPOSE: To compare the results of abdominal wall closure using interrupted synthetic short-term vs. long-term tensile strength-retaining absorbable sutures. METHODS: The subjects were 55 patients undergoing elective laparotomy through a midline vertical incision for gastric or colon cancer surgery between November 2008 and August 2010, at our hospital. After providing informed consent, the patients were randomized for suturing with Polysorb(®), which provides short-term tensile strength, or with PDS(®)II, which provides long-term strength. The primary outcome analyzed was the incidence of incisional hernia or wound dehiscence. RESULT: There were 28 patients allocated to the Polysorb group and 27 to the PDS II group. Postoperative wound dehiscence was noted in two patients (3.6%). Five of 51 patients (9.8%) suffered incisional hernia within 1 year after surgery, 6 of 41 patients (14.6%) within 2 years, and 6 of 35 patients (17.1%) within 3 years. There was no significant per year difference in the incidence of incisional hernia or wound dehiscence between the groups. CONCLUSION: Outcomes were favorable in both groups and not inferior to reported outcomes of larger-scale studies. Verification of the equivalence between the two types of suture material necessitates larger-scale studies that adopt the same suture methods.

Screening of alternative drugs to the tumor suppressor miR-375 in esophageal squamous cell carcinoma using the connectivity map.

OBJECTIVE: The aim of this study was to identify alternative compounds to the tumor suppressor miR-375 using the connectivity map (CMAP) and to validate the antitumor effects of the identified drugs in esophageal squamous cell carcinoma (ESCC). METHODS: Gene profiling of miR-375-treated TE2 and T.Tn cells was applied in order to search the CMAP database. Among the compounds identified using the CMAP, we focused on 8 drugs [(-)-epigallocatechin-3-gallate, metformin, rosiglitazone among others], excluding 2 drugs among the top 10 compounds. We evaluated whether these compounds possess tumor-suppressive functions in ESCC. RESULTS: A cytotoxicity assay showed that the sensitivity of TE2 and T.Tn cells treated with the 8 compounds was evaluated based on IC50 values of 42.9 µM to 3.8 mM. A cell cycle analysis revealed that the percentage of TE2 and T.Tn cells incubated with 6 compounds in the G0/G1 phase or the G2/M phase increased by approximately 40-80%. A TUNEL assay showed that the percentages of apoptotic cells treated with almost all compounds were significantly increased (p < 0.05) compared with the control cells. CONCLUSION: The CMAP database is a useful tool for identifying compounds affecting the same molecular pathways, particularly products that are difficult to apply via practical approaches, such as microRNAs.

A flexible-arm liver retractor that provides an optimal surgical field without postoperative liver dysfunction.

BACKGROUND/AIMS: It is important to retract the lateral liver segment during laparoscopic gastrectomy to achieve an optimal surgical field. Few retractors cause transient liver dysfunction after surgery; therefore, for an easier and safer procedure, we devised a new liver retractor and implemented a trial clinical application. METHODOLOGY: The novel liver retractor comprises a metallic, flexible arm retractor attached to the operating table and an air compressor which pneumatically moves and fixes the retractor. It was inserted directly into the abdominal cavity just below the xiphisternum to retract the left lobe of the liver anterosuperiorly, thereby exposing the hiatus. Blood samples were collected from the patients on days 1, 3, and 7 after surgery to assess the levels of the liver enzymes AST and ALT. RESULTS: During laparoscopic gastrectomy, no liver damage was observed macroscopically. The surgical fields obtained were optimal and efficient for laparoscopic surgery. Notably, it was possible to retract the liver as often as needed. Further, none of the patients developed postoperative liver dysfunction. CONCLUSIONS: The novel flexible-arm retractor provided an optimal surgical field without inducing liver dysfunction.

A case of inferior phrenic artery injury after chest drainage treated laparoscopically.

Chest drainage is a commonly performed surgical procedure. However, caution is required when performing this procedure because of its serious complications. One complication is vascular injury. Endovascular treatment has been prioritized in patients requiring hemostasis. We report the case of an 87-year-old woman, who presented to our hospital with dyspnea caused by massive pleural effusion. We decided to perform chest tube placement for the purpose of diagnosis and treatment. The inferior phrenic artery was injured during chest drainage, resulting in hemorrhagic shock. Catheter embolization was considered, but it was deemed difficult due to the patient's abnormal blood vessel. Instead, hemostasis was induced via laparoscopy. This is the first report on the safety of laparoscopic hemostasis for inferior phrenic artery bleeding. By devising, we were able to perform hemostatsis safely under laparoscopy.

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

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

COX2 expression predicts resistance to chemoradiotherapy in esophageal squamous cell carcinoma.

PURPOSE: The overexpression of cyclooxygenase (COX)2 is correlated with carcinogenesis, tumor progression, and prognosis, and increased COX2 expression is correlated with radiation resistance. However, no correlation between the COX2 expression and resistance to chemoradiotherapy for esophageal squamous cell carcinoma has been characterized. The purpose of the present study was to evaluate whether COX2 expression is an indicator of resistance to chemoradiotherapy in esophageal squamous cell carcinoma and the feasibility of COX2 as a biomarker for CRT. METHODS: Fifty-eight patients who were diagnosed with esophageal squamous cell carcinoma from biopsy samples were enrolled in the present series. All patients underwent concurrent chemoradiotherapy in a neoadjuvant setting, followed by radical esophagectomy. COX2 expression was evaluated by immunohistochemical staining and statistically compared with the histopathologic findings in surgically resected specimens. RESULTS: The rate of responders was 87% for weak expression of COX2, 62% for moderate expression, and 30% for strong expression, and there was a close correlation between COX2 expression and the response rate (Kendall's τb = 0.396, P = 0.001). In the univariate analysis, negative or weak expression of COX2 was found to correlate significantly with CRT response (odds ratio, 6.296; 95% confidence interval (CI), 1.58-25.096; P = 0.010). In the multivariate analysis, weak expression of COX2 (30% or less) was found to be an independent prognostic factor (odds ratio, 6.534; 95% CI, 1.535-27.803; P = 0.011). CONCLUSIONS: The COX2 expression predicts resistance to chemoradiotherapy in esophageal squamous cell carcinoma, and it also is a feasible biomarker for evaluating the CRT response.

Combinatory gene therapy with electrotransfer of midkine promoter-HSV-TK and interleukin-21.

UNLABELLED: We examined the effect of the combination of herpes simplex virus type1-thymidine kinase (HSV-TK)-suicide gene therapy and interleukin-21 (IL-21) immune gene therapy. MATERIALS AND METHODS: To improve tumor specificity and the safety of gene therapy, we designed the suicide gene (HSV-TK) to be driven by midkine (MK) minimal promoter (MKp-TK). Plasmid DNA containing HSV-TK-suicide gene or IL-21 gene was injected into TE2 and Colon26 tumors developed in nude mice and electric pulses were then delivered. RESULTS: Tumors transduced with the MKp-TK gene demonstrated increased sensitivity to ganciclovir (GCV) in vitro and in vivo. MK minimal promoter conferred efficient transcriptional activity to the HSV-TK-suicide gene and in vivo electroporation was an effective method for transducing the MKp-TK gene. IL-21-transduced tumors disappeared completely in syngeneic BALB/c mice. However, the tumors were not suppressed completely in T-cell-depleted nude mice, and antitumor effects were absent in NK-cell-depleted mice. These data suggest that IL-21 induces T- and NK-cell-dependent antitumor effects. Furthermore, the growth of IL-21-producing tumors subsequently transduced with MKp-TK by electroporation was significantly retarded compared with control groups. CONCLUSION: Using the minimal promoter region of MK to drive the HSV-TK gene and in vivo electroporation to transduce IL-21 DNA into the tumors produced an efficient gene therapy with improved safety. To our knowledge, this is the first report of a combination gene therapy using HSV-TK/GCVand IL-21.

Laparoscopic double-tract reconstruction after total gastrectomy for postoperative duodenal surveillance: Case series.

INTRODUCTION: When gastric cancer or carcinoid patients have coexisting diseases such as duodenal adenoma, FAP, or Crohn's disease, periodic observation of the duodenum is necessary. METHODS: Between August 2013 and April 2015, we performed four consecutive laparoscopic total gastrectomies with double tract reconstruction for duodenal surveillance. Three of the patients were diagnosed with gastric cancer, while the remaining patient was diagnosed with gastric carcinoid. RESULTS: No deaths occurred, and three of the patients showed no early complications. One patient with Crohn's disease developed anastomotic leakage, but it was successfully managed conservatively. On endoscopy three to seven months later, we were able to observe the duodenum via jejunal anastomosis in all of the patients. DISCUSSION: Roux-en-Y reconstruction is one of the options after laparoscopic total gastrectomy. However, given that periodical endoscopic examinations of the duodenum are strongly recommended after surgery, double-tract reconstruction may be preferable in these patients. CONCLUSION: Although more detailed data are required, double-tract reconstruction may be the best choice for patients requiring total gastrectomy with regular check-up of the duodenum.

Histone deacetylase inhibitor FK228 activates tumor suppressor Prdx1 with apoptosis induction in esophageal cancer cells.

PURPOSE: The histone deacetylase inhibitor FK228 shows strong activity as a potent antitumor drug but its precise mechanism is still obscure. The purpose of this study is to reveal the effect of FK228 on gene expression in the cell and to determine the mechanism of the antitumor activity of FK228 for further clinical applications. EXPERIMENTAL DESIGN AND RESULTS: Microarray analysis was applied to verify the gene expression profiles of 4,608 genes after FK228 treatment using human esophageal squamous cell cancer cell lines T.Tn and TE2. Among them, peroxiredoxin 1 (Prdx1), a member of the peroxiredoxin family of antioxidant enzymes having cell growth suppression activity, as well as p21(WAF1), were significantly activated by FK288. In addition, FK228 strongly inhibited the cell growth of T.Tn and TE2 by the induction of apoptosis. Further, chromatin immunoprecipitation analysis revealed that FK228 induced the accumulation of acetylated histones H3 and H4 in Prdx1 promoter, including the Sp1-binding site. In mouse xenograft models of T.Tn and TE2 cells, FK228 injection resulted in significant tumor regression as well as activated Prdx1 expression in tumor tissues. Prdx1 suppression by RNA interference hindered the antitumor effect of FK228. CONCLUSION: Our results indicate that the antitumor effect of FK228 in esophageal cancer cells is shown at least in part through Prdx1 activation by modulating acetylation of histones in the promoter, resulting in tumor growth inhibition with apoptosis induction.

Probable IgG4-related sclerosing disease presenting as a gastric submucosal tumor with an intense tracer uptake on PET/CT: a case report.

A 44-year-old man consulted an internist because of abnormalities in an upper gastrointestinal series. It showed an elevated lesion with central depression in the greater curvature of the middle part of the stomach. Upper gastrointestinal endoscopy showed an elevated lesion with central depression, bridging hold, and no abnormalities of the gastric mucosa in the greater curvature of the middle part of the stomach. Endoscopic ultrasonography showed a submucosal tumor derived from the muscle layer of the stomach. Computed tomography showed a 22-mm tumor in the upper part of the stomach. Integrated position emission tomography/computed tomography (PET/CT) showed an intense tracer uptake by the tumor. Based on these findings, a gastrointestinal stromal tumor was suspected and laparoscopic endoscopic cooperative surgery was performed. A histopathological examination showed lymphoplasmacytic infiltration and fibrosis, and an immunohistochemical analysis showed the infiltration of IgG4-positive lymphoplasmacytic cells. The probable diagnosis was IgG4-related sclerosing disease of the stomach. We herein describe a rare case of probable IgG4-related sclerosing disease which presented as a gastric submucosal tumor. PET/CT is a useful imaging technique for the diagnosis and follow-up of this disease.