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Compared with laparoscopic surgery (LS), robotic surgery (RS) is considered to have acceptable outcomes in rectal cancer, but few reports have focused on chylous ascites in RS. The aim of this study was to investigate the incidence and etiology of chylous ascites after RS.This retrospective study included 291 patients with rectal cancer who underwent RS (n = 165) or LS (n = 126) with high ligation of the inferior mesenteric artery (IMA). Propensity score matching (PSM) was performed to compare the two groups.\Dissection around the IMA was achieved using ultrasonic coagulating shears in most LS cases, and monopolar scissors in most RS cases, sometimes using bipolar vessel sealing device or bipolar forceps. The incidence of chylous ascites was 12.2% in RS and 4.1% in LS after PSM (P = .037). When limited to the RS group, multivariate analysis identified absence of lymphatic sealing at the left side of the IMA and shorter operative time as independent risk factors for chylous ascites. Except for duration of drain placement, no outcomes differed significantly with or without chylous ascites. One patient with chylous ascites developed later infection and required antibiotic treatment.The incidence of chylous ascites is significantly higher in RS than in LS, and RS with incomplete lymphatic sealing around the IMA is a risk factor for chylous ascites in rectal cancer. Although outcomes for patients with chylous ascites were acceptable, adequate lymphatic sealing during dissection around the IMA is crucial to prevent chylous ascites in RS.

Background: One of the complications of endoscopic surgery is port-site hernia. The risk of port-site hernia is minimized by proper port-site closure, which relies on appropriate characterization of the fascia, particularly the direction of fascial fissures. Methods: The following 4 procedures were examined to identify the fascial fissure direction: mobility of the port, observation from the lumen of the port, palpation for fascia, and visual confirmation. The match rate of each procedure with visual confirmation was verified. Results: 51 port-sites without fasciotomy were examined. The direction of the fissure was from 12 to 6 o’clock in 11 cases and 3 to 9 o’clock in 40 cases. The match rate between mobility and the fissure was 45.1%. The match rate of observation from the lumen was 96.1%. Comparing the suturing time, the average time was significantly shortened to 327 seconds in the second half compared to 494 seconds in the first half of our study period with the VersaOneTM fascial closure system. Conclusion: Treatment of port-site hernia can be done by suture or mesh repair, although ideally it is best to prevent the hernia in the first place. The fissure direction was almost always identifiable via observation from the lumen of the port. Closure of the port-site using modified Z-sutures allowed for full fascial closure, particularly in cases of patients with obesity.

Recurrence-free survival and 5-year survival rates are still commonly used as prognostic indicators for gastrointestinal cancer. We believe that there is a need to find an appropriate index to evaluate changes in health status over time in postoperative patients. We evaluated changes in "frailty" after esophageal cancer surgery using the Kihon Checklist (KCL) developed by the Japanese Ministry of Health, Labour and Welfare, and examined risk factors for worsening health status after surgery. Twenty-four patients (21 thoracoscopic sub-total esophagectomy, 1 mediastinoscopic sub-total esophagectomy, and 2 total laryngopharyngoesophagectomy) who underwent esophageal cancer surgery in our department from December 2019 to April 2021 were included. Patients were asked to write down their KCL before surgery and one year after surgery at an outpatient clinic, and changes over time were checked. We compared the background factors in the "maintain" group (M group) and the "worsened" group (W group), and investigated the risk factors for pre-frail and frail states one year after the surgery. 8 patients worsened from robust to pre-frail to frail and pre-frail to frail, and 16 patients maintained their condition, with 33% of them worsening. Age (M/W: 70/72, p=0.296), male (M/W: 0.88/1.0, p=0.536), BMI (M/W: 22.4/19.6, p=0.142), pStage≥3 (M/W: 0.38/0.38, p=1.0), preoperative chemotherapy (M/W: 0.69/0.63, p=1.0), operative time (M/W: 566/610 minutes, p=0.327), blood loss (M/W: 103/151 ml, p=0.342), postoperative pneumonia (M/W: 0.25/0.25, p=1.0), and cancer recurrence (M/W: 0.19/0.50, p=0.167). The preoperative blood samples were Alb (M/W: 4.3/3.8 g/dl, p=0.046), Hb (M/W: 14.2/12.8 g/dl, p=0.015) and Cre (M/W: 0.85/0.79 mg/dl, p=0.713). At 1 year after esophageal cancer surgery, health worsened and 33% of patients were in a pre-frail or frail state. Risk factors for worsening health were low Alb and low Hb, which were not related to stage or actual age. Further study is needed to clarify risk factors for frailty.

Situs inversus totalis is defined as a complete mirror-image transposition of the thoracic and abdominal viscera. Cancer surgery in patients with situs inversus totalis can be more difficult than in patients without situs inversus totalis; however, robotic surgery using the da Vinci Surgical System allows for intuitive operation with its multi-articular function and stereopsis effect. In addition, prevention of shaking and the motion scale allows for efficient surgical procedures. We evaluated a 64-year-old man who had gastric cancer, and situs inversus totalis and a blood-vessel variation. To facilitate intuitive handling of the robot in this patient with organs reversed from the norm, we arranged the instruments and ports in such a way that the Maryland bipolar forceps could be used with the surgeon’s right hand. We performed a successful robotic distal gastrectomy with lymph node dissection. The operative time was 286 min, and the blood loss was 44 mL. There were no intra- or post-operative complications. The patient was discharged on postoperative day 7 and has had no evidence of a recurrence for 18 months. We conclude that robotic surgery is an efficient tool for operating on patients with gastric cancer, and situs inversus totalis and vessel variations.

Background: Anastomotic leakage is a serious complication in colorectal surgery, often associated with higher morbidity and mortality. Even with advances in medical technology and devices, the rates of anastomotic leakage is not on downward trend. We describe our experimental and clinical validation of our method to overcome the weakness of the double stapling technique, especially the intersecting staple lines. Methods: Experimentally, we conducted double stapled anastomosis with pig small intestines. In order to verify pressure resistance, the anastomosis was tested and compared with that formed by a conventional stapler and a reinforced cartridge preattached to a Neoveil sheet. Additionally, during the anastomosis performed by the circular stapler, both ends of the Neoveil sheet were grasped by forceps, and the Neoveil sheet was pulled tight to fit the anastomotic surface. The burst pressure of the anastomosis was recorded. Clinically, we used a reinforced cartridge for rectal surgery performing a low anterior resection and verified its efficacy and safety. Results: Unlike a conventional stapler, our methods with the use of a reinforced cartridge showed no leakage from the intersecting staple lines. Clinically, our method has been used for 20 patients without complications, including leakage and bleeding. Conclusion: The addition of reinforcing material to the linear stapler should lead to increased strength of the anastomosis. We believe that a double stapling anastomosis that uses our method for the intersection lines provides increased safety and security and thereby should lead to a reduced rate of suture failure after rectal resection.

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Few studies have investigated or verified the pressure resistance of anastomosis with circular staplers. We conducted end-to-end anastomoses with circular staplers and compared the pressure resistance with or without bioabsorbable material (Neoveil NanoⓇ). We conducted end-to-end anastomosis with or without Neoveil NanoⓇ (NN). Fresh pig small intestines were used. An end-to-end anastomosis was performed between two intestinal specimens using a circular stapler. The burst pressure of the anastomosis was recorded. The group with the highest pressure resistance was the group in which NN was attached only to the anvil, which was higher than the group in which NN was attached to the shaft and anvil. In contrast, no increase in pressure resistance occurred in the group using NN only for the shaft. Clinically, this method was used for various anastomoses using a circular stapler. In the absence of NN, a portion of the staple was often exposed at the anastomosis. When NN was used, however, only a small amount of the staple was exposed. There were no complications that were associated with NN. The usefulness of NN for pressure resistance of anastomosis with a circular stapler was demonstrated. The pressure resistance was highest by attaching NN only to the anvil of the stapler. Use of a circular stapler significantly reduces the complication associated with an anastomosis.

The acquisition of resistance to apoptosis is one of the biggest problems in colorectal cancer (CRC) treatment. This study aimed to elucidate the mechanisms of resistance to apoptosis with a focus on interleukin (IL)-6 produced by the interaction between cancer cells and cancer-associated fibroblasts (CAFs).DLD-1 and HCT116 cell lines were treated with IL-6 and furthermore co-cultured with CAFs. The expression levels of Bcl-xL, Mcl-1 and phosphorylation of STAT3 were evaluated by western blotting. We also performed immunostaining for CRC specimens and evaluated the correlation between CAFs invasion and Bcl-xL/Mcl-1 expression.Both IL-6 and co-culturing enhanced Bcl-xL, Mcl-1 and the phosphorylation of STAT3. Immunohistochemistry showed a positive correlation between CAFs and Bcl-xL/Mcl-1. These results showed that the interaction between CAFs and cancer cells enhances Bcl-xL and Mcl-1 through the IL-6/STAT3 signaling pathway.Our findings provide new potential therapeutic targets and strategies for CRC treatment.

Description, Intake of specific seven essential amino acids affects the pathology of the brain., Protein malnutrition is epidemiologically suggested as a potential risk factor for senile dementia, although molecular mechanisms linking dietary proteins and amino acids to neurodegeneration remain unknown. Here, we show that a low-protein diet resulted in down-regulated expression of synaptic components and a modest acceleration of brain atrophy in mice modeling neurodegenerative tauopathies. Notably, these abnormal phenotypes were robustly rescued by the administration of seven selected essential amino acids. The up-regulation of inflammation-associated gene expression and progressive brain atrophy in the tauopathy model were profoundly suppressed by treatment with these essential amino acids without modifications of tau depositions. Moreover, the levels of kynurenine, an initiator of a pathway inducing neuroinflammatory gliosis and neurotoxicity in the brain, were lowered by treatment through inhibition of kynurenine uptake in the brain. Our findings highlight the importance of specific amino acids as systemic mediators of brain homeostasis against neurodegenerative processes.

The cancer-stromal interaction has been demonstrated to promote tumor progression, and cancer-associated fibroblasts (CAFs), which are the main components of stromal cells, have attracted attention as novel treatment targets. Chitinase 3-like 1 (CHI3L1) is a chitinase-like protein, which affects cell proliferation and angiogenesis. However, the mechanisms through which cells secrete CHI3L1 and through which CHI3L1 mediates tumor progression in the cancer microenvironment are still unclear. Accordingly, the present study assessed the secretion of CHI3L1 in the microenvironment of colorectal cancer and evaluated how CHI3L1 affects tumor angiogenesis. CAFs and normal fibroblasts (NFs) established from colorectal cancer tissue, and human colon cancer cell lines were evaluated using immunostaining, cytokine antibody array, RNA interference, reverse transcription-quantitative PCR (RT-qPCR), ELISA, western blotting and angiogenesis assays. The expression and secretion of CHI3L1 in CAFs were stronger than those in NFs and colorectal cancer cell lines. In addition, interleukin-13 receptor α2 (IL-13Rα2), a receptor for CHI3L1, was not expressed in colorectal cancer cell lines, but was expressed in fibroblasts, particularly CAFs. Furthermore, the expression and secretion of IL-8 in CAFs was stronger than that in NFs and cancer cell lines, and recombinant CHI3L1 addition increased IL-8 expression in CAFs, whereas knockdown of CHI3L1 suppressed IL-8 expression. Furthermore, IL-13Rα2 knockdown suppressed the enhancement of IL-8 expression induced by CHI3L1 treatment in CAFs. For vascular endothelial growth factor-A (VEGFA), similar results to IL-8 were observed in an ELISA for comparison of secretion between CAFs and NFs and for changes in secretion after CHI3L1 treatment in CAFs; however, no significant differences were observed for changes in expression after CHI3L1 treatment or IL-13Rα2 knockdown in CAFs assessed using RT-qPCR assays. Angiogenesis assays revealed that tube formation in vascular endothelial cells was suppressed by conditioned medium from CAFs with the addition of human CHI3L1 neutralizing antibodies compared with control IgG, and also suppressed by conditioned medium from CAFs transfected with CHI3L1, IL-8 or VEGFA small interfering RNA compared with negative control small interfering RNA. Overall, the present findings indicated that CHI3L1 secreted from CAFs acted on CAFs to increase the secretion of IL-8, thereby affecting tumor angiogenesis in colorectal cancer.

Background Spontaneous esophageal rupture is a rare but serious disease with high mortality. Conservative treatment and endoscopic therapy have been reported, but surgical treatment is still a basic modality of therapy. In addition to thoracotomy, recent studies have reported treatment with thoracoscopic surgery and laparoscopic transhiatal repair. In this study, we report a patient who underwent laparoscopic transhiatal suture closure for spontaneous esophageal rupture with favorable postoperative course. We also discuss indication for laparoscopic surgery for spontaneous esophageal rupture. Case presentation A 70-year-old man visited our hospital with chief complaints of epigastric pain and vomitus niger. He was diagnosed with spontaneous esophageal rupture in the left wall of the lower esophagus by computed tomography and upper gastrointestinal (GI) series. At 11 h after the onset of symptoms, we performed laparoscopic transhiatal suture closure and lavage drainage. We performed transhiatal esophageal replacement using the 5-hole approach. We observed a perforation of 2 cm in diameter at the site of the rostral portion approximately 4 cm from the esophageal hiatus. All layers were closed with three stitches using 3–0 absorbable sutures. No perforation was observed in the thoracic cavity. The total operative time was 178 min, and total bleeding was 2 ml. He had no postoperative complications and was discharged on day 15 after the procedure. He received continuous proton pump inhibitor therapy as an outpatient. Healing cicatrization was found at the site of rupture by esophagogastroscopy. The patient was advised to improve his lifestyle and has shown no signs of recurrence over 2 years from the date of surgery. Conclusions Simple closure of all the layers using laparoscopic transhiatal simple closure was useful in the treatment of esophageal rupture as a less invasive approach for patients who meet the following conditions: stable general condition, intrathoracic perforation, and the perforation site is identified as the lower esophagus by pre-operative examination.

One of the complications in laparoscopic surgery is port-site hernia. It is a rare but potentially dangerous complication. Especially when using ports with a size 10 mm or more, it is required to securely close the port site. However, this procedure is often difficult especially for obese patients. We herein devised a new closure method by using a device developed for port site. These techniques are methods that can close the port site by a combination of putting in and out of thread and port rotation without removing a port. The port-site closure with these techniques was done for 53 port sites of 41 patients. The port site was closed horizontally or vertically, depending on the shape of the port site for two patients. Modified Z-suture was done for other 37 patients. To date, we have not noted any complications from this new method, including port-site hernia. With our technique, we could save operation time and reduce stress of us especially for obese patients. We would like to increase the number of patients and verify the safety and usefulness in further study.

The use of laparoscopic surgery has become widespread in recent years. One of its complications is port site hernia (PHS). It can be difficult to close the fascia at the time of laparoscopy, especially in obese patients, and there is a risk of herniation through a fascial defect with incomplete closure. It is important to ascertain closure of the defect when repairing PHS to prevent recurrence. We report a 47-year-old woman who developed a PHS at the superior aspect of the umbilicus. We repaired the defect using the VersaOneTM Fascial Closure System with laparoscopic guidance. This system allows the port site to be reliably closed while observing the suture from the abdominal cavity. The incision is the same size as a port site. If the abdominal wall is thick and the PHS has a diameter of ~10 mm, this method is considered to be indicated, regardless of the site.

We previously showed that oral administration of cystine and theanine (CT) to mice confers resistance to influenza virus infection. In human studies, CT prevented colds in healthy subjects and enhanced antibody production after influenza vaccination in elderly individuals with a poor nutritional status. The mechanism of action of CT is thought to be glutathione (GSH)-mediated regulation of intracellular redox, which might affect innate immune systems such as macrophages to exert physiological effects. The effect of CT on influenza is independent of viral type, and this treatment has a broad range of antiviral activities. To explore the mechanisms of CT in viral infection, we performed transcriptome profiling of spleen tissues isolated from influenza A virus (IAV)-infected mice. We identified unique gene signatures in response to CT in the IAV-infected mice. Genes upregulated by CT included redox-regulated genes such as GCLC/GCLM (subunits of glutamate cysteine ligase, a rate-limiting enzyme of GSH biosynthesis), TXN1, TXN2, TXNRD2, and SOD1, suggesting that the intracellular redox environment is substantially altered by CT. However, genes downregulated in response to CT included chemokine/chemokine receptor genes (CCL5, CCL19, CXCL9, CXCL12, CXCR3, CXCR4, and ACKR3), some of which are related to cytokine storm. A comparison with public COVID-19-related gene set data showed that the upregulated gene signature was highly similar to the downregulated gene sets of SARS-CoV/SARS-CoV-2-infected cells and the upregulated gene set of attenuated SARS-CoV-infected cells. In conclusion, the unique gene signatures observed in response to orally administered CT in IAV-infected mouse spleen tissues suggested that CT may attenuate viral infection, replication and associated symptoms such as cytokine storm.

// Yuji Toiyama 1 , Yoshinaga Okugawa 1 , Satoru Kondo 1 , Yoshiki Okita 1 , Toshimitsu Araki 1 , Kurando Kusunoki 2 , Motoi Uchino 2 , Hiroki Ikeuchi 2 , Seiichi Hirota 3 , Akira Mitsui 4 , Kenji Takehana 5 , Tsutomu Umezawa 5 and Masato Kusunoki 1 1 Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Graduate School of Medicine, Mie University, Mie, Japan 2 Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan 3 Department of Surgical Pathology, Hyogo College of Medicine, Hyogo, Japan 4 Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan 5 RD methylation; ulcerative colitis Abbreviations: AUC: area under the ROC curve; CRC: colorectal cancer; FFPE: formalin-fixed paraffin-embedded; ROC: received operating characteristic; UC: ulcerative colitis Received: June 19, 2018 Accepted: August 10, 2018 Published: September 04, 2018 ABSTRACT Background: There are no biomarkers to facilitate the identification of patients with ulcerative colitis (UC) who are at high risk for developing colorectal cancer (CRC). In our current study, we used rectal tissues from UC patients to identify aberrant DNA methylations and evaluated whether they could be used to identify UC patients with coexisting colorectal neoplasia. Results: Using a training set, we identified 484 differentially methylated regions (DMRs) with absolute delta beta-values > 0.1 in rectal mucosa by using the ChAMP algorithm. Next, pathway enrichment analysis was performed using 484 DMRs to select coordinately methylated DMRs, resulting in the selection of 187 aberrant DMRs in rectal tissues from UC-CRC. Then, the Elastic Net classification algorithm was performed to narrow down optimal aberrant DMRs, and we finally selected 11 DMRs as biomarkers for identification of UC-CRC patients. The 11 chosen DMRs could discriminate UC patients with or without CRC in a training set (area under the curve, 0.96) and the validation set (area under the curve, 0.81). Conclusions: In conclusion, we identified 11 DMRs that could identify UC patients with CRC complications. Prospective studies should further confirm the validity of these biomarkers. Methods: We performed genome-wide DNA methylation profiles in rectal mucosal tissues ( n = 48) from 24 UC-CRC and 24 UC patients in a training set. Next, we performed comprehensive DNA methylation analysis using rectal mucosal tissues ( n = 16) from 8 UC-CRC and 8 UC patients for validation.

Background Few studies have investigated the burst pressure of side-to-side anastomoses comparing different stapling devices that are commercially available. Objectives We conducted side-to-side anastomoses with a variety of staplers and compared burst pressure in the crotch of the anastomoses. Setting Nagoya City East Medical Center. Methods We conducted side-to-side anastomoses with 9 staplers with different shapes and forms. Fresh pig small intestines were used. A side-to-side anastomosis was performed between 2 intestine specimens using a linear stapler. The burst pressure of the anastomosis was recorded. Results In total, 45 staplers were used for this experiment. The site of leakage in all cases was the crotch. Regarding the influence of the number of staple rows, the burst pressure in 3-row staplers was significantly higher than in 2-row staplers. With regard to the relationship between staple height and burst pressure, staples with a height slightly shorter than the intestinal thickness showed the highest burst pressure. In a comparison of staplers with uniform staple heights and stamplers with staples of 3 different heights, the latter had significantly lower burst pressures. Neoveil significantly increased the burst pressure in the crotch and contributed to the highest burst pressure of all the staplers used in this experiment. Conclusions In this experiment, we defined the important factors that influence burst pressure at the crotch of a stapled, side-to-side anastomosis. These factors include the number of staple rows, the height of the staple compared with the thickness of the tissue, uniformity of staple height, and reinforcement of the staple line. In any surgical case requiring intestinal anastomosis, selection of a stapler is a critical step.

// Hideyuki Ishiguro 1, * , Tomotaka Okubo 1, * , Yoshiyuki Kuwabara 1 , Masahiro Kimura 1 , Akira Mitsui 1 , Nobuyoshi Sugito 1 , Ryo Ogawa 1 , Takeyasu Katada 1 , Tatsuya Tanaka 1 , Midori Shiozaki 1 , Koji Mizoguchi 1 , Yosuke Samoto 1 , Yoichi Matsuo 1 , Hiroki Takahashi 1 and Shuji Takiguchi 1 1 Nagoya City University Graduate School of Medicine, Department of Gastroenterological Surgery, Mizuho-ku, Nagoya 467-8601, Japan * These authors have contributed equally to this work Correspondence to: Hideyuki Ishiguro, email: h-ishi@med.nagoya-cu.ac.jp Keywords: colon cancer, β-catenin, NOTCH1, NICD1, prognosis Received: May 29, 2016 Accepted: June 27, 2017 Published: July 25, 2017 ABSTRACT Purpose and Methods: The translocation of β-catenin/CTNNB1 to the nucleus activates Wnt signaling and cell proliferation; however, the precise mechanism underlying this phenomenon remains unknown. Previous reports have provided evidence that NOTCH1 is involved in the Wnt signaling pathway. Therefore, we sought to determine the mechanism by which NOTCH1 influences the Wnt/β-catenin pathway. We constructed a vector expressing the NOTCH1 intracellular domain (NICD1) and transfected the vector into HCT116 which has low expression of NICD1. Furthermore, inhibition of NOTCH signal pathway in SW480 which has abundant NICD1 expression, was performed by transfection of siNICD1 or DAPT, gamma secretase inhibitor, treatment. In addition, we evaluated NICD1 and β-catenin localization in colon cancer cell lines and in 189 colon cancer tissue samples and analyzed the correlation between the nuclear localization of NICD1 and the clinicopathological features of colon cancer patients. Results: Immunohistochemical assays demonstrated that NICD1 and β-catenin exhibited a similar localization pattern in colon cancer tissues. In addition, we found that NICD1 induced the translocation of β-catenin to the nucleus and that NICD1 and β-catenin co-localized in the nucleus. Overexpression of NICD1 increased luciferase activity of Wnt signal pathway. On the other hand, reduction of NICD1 reduced luciferase activity of Wnt signaling pathway. In the 189 analyzed colon cancer cases, multivariate COX regression analysis demonstrated the independent prognostic impact of nuclear localization of NICD1(p=0.0376). Conclusion: NOTCH1 plays a key role in the Wnt pathway and activation of NOTCH1 is associated with the translocation of β-catenin to the nucleus.

Highlights • The indications for stripping of the esophagus have decreased due to the widespread of endoscopic mucosal resection and thoracoscopic surgery. • Even if indications for this procedure have decreased, this is an important option in the armamentarium of the esophageal surgeon., Introduction Patients with esophageal cancer frequently cannot tolerate thoracotomy due to their overall debilitated condition. Moreover, some patients have severe adhesions in the thoracic cavity. Eversion stripping of the esophagus is an option for resection in these patients. Presentation of case A 64-year-old man was admitted to our institution with the chief complaint of epigastric pain. Endoscopic examination showed a protruding lesion 22 cm from the incisors, with a superficial and circumferential mucosal irregularity on the distal side of the lesion. Biopsy revealed squamous cell carcinoma. Clinical stage was T1b(sm)N0M0, cStage I. In addition to the poor pulmonary status of the patient, adhesions in the intrathoracic cavity were predicted. The decision was made to perform esophageal resection without a thoracotomy. In order to ensure complete invagination of the esophagus, the esophagus was insufflated prior to stripping. The stripping process was observed with a gastroscope. During the stripping, the esophagus did not bunch up, and stripping was smooth and with minimal resistance. Discussion The stripping resection of the esophagus is an important option for the esophageal surgeon. In this case report, we describe a new eversion stripping method of the esophagus. This easy and reliable stripping method incorporates intraesophageal insufflation. Conclusion The indications for blunt esophageal dissection without thoracotomy have been decreasing. On the other hand, our method seems to be useful in optimal case of stripping of esophagus.

Introduction Various types of staplers are used for gastric tube formation after esophagectomy. Using a stapling device, a gastric tube can safely be created in a short amount of time. The problems with gastric tube creation using only linear type staplers include staple overlap as well as the problem of cost associated with using multiple staplers. To address this, both linear and radial type staplers have been introduced. We herein compare three methods of gastric tube creation. Methods From 2012 to 2014, 62 patients with esophageal cancer underwent esophagectomy with gastric tube reconstruction. We evaluated and compared the mean number of stapler loads and cost in each groups. Results The mean number of stapler loads was 6.24 in method A, 5.16 in method B, and 4.33 in method C. The mean cost accounting for total staple fires per case was 3116.07 dollars in the method A group, 2576.74 dollars in the method B group, and 2447.78 dollars in the method C group. Anastomotic leaks developed in 4 cases in the method A group and in 3 cases in the method B group. There were no anastomotic leaks in the method C group. Conclusion We hypothesize that by using radial type staplers, we can create a durable gastric tube and reduce the number of staplers and therefore reduce operative cost., Highlights • We herein compare three methods of gastric tube creation. • Using radial type staplers, we can create a durable gastric tube. • We also reduce the number of staplers and therefore reduce operative cost.

A 44-year-old woman with advanced metastatic colon cancer received chemotherapies comprising oxaliplatin and capecitabine (XELOX), irinotecan hydrochloride, leucovorin calcium and fluorouracil irinotecan (FOLFIRI)/panitumumab and mFOLFOX6/bevacizumab. Fifteen months later, she presented with the acute onset of a headache, drowsiness and seizure with a fever and hypertension. Brain magnetic resonance imaging (MRI) indicated bilateral regions of signal hyperintensity in the white matter with spasms of bilateral cerebral arteries apparent on magnetic resonance angiography. Posterior reversible encephalopathy syndrome (PRES) was diagnosed, and treatments resulted in improvement of the MRI findings, but the patient experienced cerebral infarction and ultimately died of deterioration of cancer on day 26 after the onset of PRES.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy and one of the more difficult diseases to diagnose in Japan due to its poor prognosis. MicroRNAs are small non-coding RNAs of 21–23 nucleotides that regulate gene expression. MicroRNA-34b (miR-34b) has been reported to be overexpressed in various types of cancer. However, its role in ESCC has yet to be extensively studied. The present study investigated the expression of miR-34b in 88 ESCC patients. The miR-34b expression in ESCC was significantly higher than that in the corresponding normal esophageal mucosa. It was more highly expressed in tumors with more advanced stages. However, its expression did not correlate with the p53 status. Transfection of anti-miR-34b to the ESCC cells suppressed cell growth in vitro. These results suggest an oncogenic role of miR in ESCC.

症例は43歳の男性で，右下腹部痛を主訴として近医受診した．急性虫垂炎様症状を呈し，保存的治療で軽快した．経過観察の腹部CTにて右下腹部の充実性腫瘤を認めた．検査所見から回腸悪性腫瘍の診断で，手術を施行した．回腸末端より約120 cmにMeckel憩室を認め，憩室先端部に腫瘍が存在した．腫瘍は膀胱右側腹壁へ浸潤し，腹膜播種と思われる小結節，腸間膜リンパ節の腫脹，肝転移を認めた．手術は腫瘍を含めたMeckel憩室の切除を行った．腫瘍は病理組織学的には，高分化型腺癌で，Meckel憩室内の異所性胃粘膜と連続していた．我々は異所性胃粘膜が発生母地と考えられたMeckel憩室癌の1例を経験したので自験例を加え，本邦報告例37例の集計および文献的考察を行った．

Thioredoxin-1 (TRX) is a small (14 kDa) multifunctional protein with the redox-active site Cys-Gly-Pro-Cys. Macrophage migration inhibitory factor (MIF) is a 12 kDa cytokine belonging to the TRX family. Historically, when we purified TRX from the supernatant of ATL-2 cells, a 12 kDa protein was identified along with TRX, which was later proved to be MIF. Here, we show that TRX and MIF form a complex in the cell and the culture supernatant of ATL-2 cells. Using a BIAcore assay, we confirmed that TRX has a specific affinity with MIF. We also found that extracellular MIF was more effectively internalized into the ATL-2 cells expressing TRX on the cell surface, than the Jurkat T cells which do not express surface TRX. Moreover, anti-TRX antibody blocked the MIF internalization, suggesting that the cell surface TRX is involved in MIF internalization into the cells. Furthermore, anti-TRX antibody inhibited MIF-mediated enhancement of TNF-alpha production from macrophage RAW264.7 cells. These results suggest that the cell surface TRX serves as one of the MIF binding molecules or MIF receptor component and inhibits MIF-mediated inflammatory signals.

To develop novel therapeutic and diagnostic methods for esophageal cancer, it is important to understand the precise biological mechanism. Micro-RNAs (miRNAs) seem to be crucial factors in diverse regulation pathways. In this study, we analyzed the expression of mature miRNAs in esophageal squamous cell carcinoma (ESCC). The expression of 73 miRNAs was quantified by qRT-PCR in 30 primary ESCC specimens. We examined the correlation between miRNA expressions and the clinicopathological factors and prognosis of ESCC. The Kaplan-Meier survival curves showed that the high expression levels of 6 of the 72 miRNAs correlated with significantly lower patient survival rates. The overexpression of miR-129 was identified as a significant and independent prognostic factor (P = 0.031) in surgically treated ESCC patients. The hazard ratio for the prediction of early death was 18.11 for high versus low expression levels of miR-129. Similar results were obtained from an analysis performed on an additional 19 patients (test cohort) (P = 0.0057, for training cohort; P = 0.011, for test cohort; log-rank test). This experiment supports the notion that the high miR-129 expression levels, as observed in this study, might play a important role in the development of esophageal cancer.

Ninety-one strains of nitrogen fixing marine blue-green algae were tested for their nutritional value for seawater adapted hybrid tilapia fry (Tilapia mossambica females x Tilapia hornorum males) with initial weights of 0.2 to 1.3 g. The majority of these blue-green algae were acceptable single ingredient feeds for the fish when the increase in wet body weight was used as a measure of food value. Twenty-two of the marine blue-green algal strains tested, belonging to the genera Nostoc, Anabaena and Calothrix, supported daily weight gains in excess of 10% when the fish were fed to excess in 5 to 7 day feeding trials. Fish fed to excess on several selected blue-green algal strains had growth rates equivalent to those of fish fed to excess on a complete ration. Excellent food conversion ratios (dry weight blue-green algae fed/wet weight gain) in the range of 1.48 to 1.81 were obtained when the fish were fed three selected nutritive blue-green algal strains at a daily rate of 10% of the body weight.

SUMMARY. Radiotherapy plays a key role in the control of tumor growth in esophageal cancer patients. To identify the patients who will benefit most from radiation therapy, it is important to know the genes that are involved in the radiosensitivity of esophageal cancer cells. Hence, we examined the global gene expression in radiosensitive and radioresistant esophageal squamous cell carcinoma cell lines. Radiosensitivities of 13 esophageal cancer cell lines were measured. RNA was extracted from each esophageal cancer cell line and a normal esophageal epithelial cell line, and the global gene expression profiles were analyzed using a 34 594-spot oligonucleotide microarray. In the clonogenic assay, one cell line (TE-11) was identified to be highly sensitive to radiation, while the other cell lines were found to be relatively radioresistant. We identified 71 candidate genes that were differentially expressed in TE-11 by microarray analysis. The up-regulated genes included CABPR, FABP5, DSC2, GPX2, NME, CBR3, DOCK8, and ABCC5, while the down-regulated genes included RPA1, LDOC1, NDN, and SKP1A. Our investigation provided comprehensive information on genes related to radiosensitivity of esophageal cancer cells; this information can serve as a basis for further functional studies.

症例は72歳，女性．腹痛を主訴に平成14年4月中旬当院救急外来を受診した．外来で点滴加療中に大量の血便とともに，ショック状態となった．腹部は軽度膨満し，全体に軽度の圧痛を認めた．右上腹部に約5横指肝を触知した．緊急CTを施行したところS状結腸壁肥厚とS状結腸内への造影剤の漏出，さらに肝右葉を占拠する約15cmの腫瘤を認めた．以上より肝転移を伴うS状結腸癌からの出血性ショックと診断し緊急開腹術を施行した．開腹所見は，骨盤内で回腸末端，回腸間膜，S状結腸腫瘍が一塊になっていた．S状結腸癌の回腸および回腸間膜浸潤と判断しこれを一塊に切除，回腸は端々吻合し，結腸は口側切離端を人工肛門としてHartmann手術を施行した．S状結腸に2型の腫瘍が存在し，その潰瘍底が回腸間膜に穿通していた．大量出血の原因は腫瘍の回腸間膜への浸潤および同部の血管の破綻と考えられた．本症例は，小腸間膜に大腸癌が浸潤，穿通し多量の血便をきたすというきわめて稀な症例であった．若干の文献的考察を加え報告した．

Purpose: MicroRNAs (miRNA) are small noncoding RNAs thought to be involved in physiologic and developmental processes by negatively regulating the expression of target genes. Little is known about the role of miRNAs in normal and cancer cells. It is possible that deregulation of miRNA may contribute to the oncogenesis of some cancers. We studied the expression level of the miRNA processing enzyme (DICER1, DGCR8, and RNASEN) in esophageal squamous cell carcinoma (ESCC). Experimental Design: The expression levels of DICER1, DGCR8, and RNASEN mRNA in 73 ESCC tissues were compared with that in corresponding normal esophageal epithelium by Taqman real-time reverse-transcription PCR. We also examined RNASEN protein expression in 27 cell lines. The role of RNASEN in cell proliferation in ESCC cells was assessed by small interfering RNA. Paraffin sections of ESCC patients were immunohistochemically investigated. Results: We found that RNASEN expression levels were enhanced in a fraction of esophageal cancers. Multivariate Cox regression analysis showed that the prognostic effect of RNASEN (P = 0.0036) seems to be independent of disease stage (P = 0.0060). Knockdown of RNASEN in esophageal cancer cell lines resulted in a 46% to 85% reduction in cell number. In an immunohistochemical study, the intensity of RNASEN expression was often increased in the tumor compared with that in normal epithelium. Conclusions: The relationship between the RNASEN expression and the prognosis of the ESCC patients warrants a further study on the role of miRNA and tumor progression.

SUMMARY. NDRG1 (N-myc downstream regulated gene-1) was reported to be necessary for p53-mediated apoptosis and to be regulated by PTEN (phosphatase and tensin homolog). In several cancers, it was suggested to be a tumor suppressor gene. Its significance in esophageal squamous cell carcinoma (ESCC) has not been studied. The objective of this study was to clarify the relation between clinicopathological and biologic factors in esophageal carcinoma and to determine the prognostic significance of the expression of NDRG1. Expression of NDRG1 mRNA was quantified by real-time reverse transcription polymerase chain reaction using a Lightcycler in 47 esophageal ESCC specimens. The data were analyzed with reference to clinicopathological factors. Among the esophageal cancer tissues, NDRG1 mRNA expression was significantly lower in tumors of more advanced pathological stage (0–I vs. II–IV; P = 0.0027) and local tumor invasion (T1–2 vs. T3–4; P = 0.0136). Patients who had low NDRG1 mRNA expression had a significantly shorter survival after surgery compared with patients who had high NDRG1 mRNA expression (log-rank test, P = 0.0478). Impaired NDRG1 expression may lead to more aggressive invasion of ESCC.

頸胸境界部の進行食道癌は，気管浸潤をきたし易く，その完全切除には縦隔気管瘻の造設が必要な場合がある。縦隔気管瘻には，致命的な合併症を高率に伴うことが報告され，これまでに，合併症を回避する目的で，種々の筋皮弁を用いた造設法が検討されてきた。今回，頸胸境界部の食道癌に対する手術法，特に縦隔気管瘻の造設法について述べる。【術式の要点】骨性前胸壁を広範囲に除去する。気管を上行大動脈と上大静脈との間より前胸壁に引き出す。全大網の付着した胃管を作製する。後縦隔経路にて大網と共に胃管を挙上する。大網を用いて，気管周囲，主要血管，吻合部を広く被覆する。【総括】頸胸境界部食道癌に対する喉頭食道全摘後の縦隔気管瘻の造設において，大網を利用する本術式は，手技が簡便・確実で，優れた造設法の一つと思われる。

High sheet resistance multilayers consisting of Ga-doped ZnO (ZnO:Ga) and Ga-Y-codoped ZnO (ZnO:Ga,Y) films were investigated. These films were deposited by DC magnetron sputtering. The sheet resistances of substrate/(ZnO:Ga,Y)/(ZnO:Ga)/(ZnO:Ga,Y) multilayers are adjustable in the range of 450–1600 Ω/sq by choosing the proper thickness of the (ZnO:Ga) layer. This is because the (ZnO:Ga,Y) layer has a high resistivity of about 1 Ω cm and does not practically contribute the sheet resistance of the multilayers. The sheet resistance of the multilayers shows almost no change after a long heating at 100°C in air. This is probably due to the improvement in crystallinity of the (ZnO:Ga) layer deposited on the (ZnO:Ga,Y) underlayer and the protection of the (ZnO:Ga) layer from its oxidation by the (ZnO:Ga,Y) overlayer.

ITO films deposited on ZrO 2 undercoats by sputtering were investigated. The ITO films have a fine grain structure, compared to a grain–subgrain structure of conventional ITO films grown on a glass substrate. The grain structure of the ITO films grown on ZrO 2 consists of 30–50 nm wide almost parallel-sided columns. The surface grains have a good uniformity in shape and size. The microstructure and electrical properties of the ITO films changed with increasing ZrO 2 thickness. This indicates that the microstructure and properties of ITO films can be controlled by the ZrO 2 film thickness. The OLED fabricated on the ITO films on ZrO 2 worked with lower driving voltage than the one fabricated on conventional ITO films at the same luminance.

In this study, we investigated activity of matrix metalloproteinase (MMP) of lung cancer by newly developed film in situ zymography (FIZ) stamp method, which allows visual localization of gelatinolytic activity within the cut surface of a tumor. We performed FIZ stamp method and conventional gelatin zymography in 39 resected specimen of lung cancer. The degree of gelatinolytic activity was scored (FIZ score) and correlated with the clinicopathological factors of the tumor. FIZ score of normal lung was very low. Lung cancer tissue had consistently higher FIZ score than the matched normal lung tissue. There were statistically significant differences in the FIZ score according to the pathological stage (P = 0.0015), nodal status (P = 0.0007) and lymphatic invasion (P = 0.0004). Direct correlation was observed between the FIZ score and MMP-2 activity (rho = 0.568, P = 0.0030) as quantitated using conventional gelatin zymography. MMP-2 may play an important role in the lymphatic invasion of lung cancer. FIZ stamp method may be a simple and useful diagnostic aid for the presence of cancer cells in the resected specimen.