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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.

Background Cisplatin-induced acute kidney injury (AKI) is common during preoperative chemotherapy for esophageal cancer. The purpose of this study was to investigate the association between AKI after preoperative chemotherapy and postoperative complications in patients with esophageal cancer. Methods In this retrospective cohort study, we included patients who had received preoperative chemotherapy with cisplatin and underwent surgical resection for esophageal cancer under general anesthesia from January 2017 to February 2022 at an education hospital. A predictor was stage 2 or higher cisplatin-induced AKI (c-AKI) defined by the KDIGO criteria within 10 days after chemotherapy. Outcomes were postoperative complications and length of hospital stays. Associations between c-AKI and outcomes including postoperative complications and length of hospital stays were examined with logistic regression models. Results Among 101 subjects, 22 developed c-AKI with full recovery of the estimated glomerular filtration (eGFR) before surgery. Demographics were not significantly different between patients with and without c-AKI. Patients with c-AKI had significantly longer hospital stays than those without c-AKI [mean (95% confidence interval (95%CI)) 27.6 days (23.3–31.9) and 43.8 days (26.5–61.2), respectively, mean difference (95%CI) 16.2 days (4.4–28.1)]. Those with c-AKI had higher C-reactive protein (CRP) levels and prolonged weight gain after surgery and before the events of interest despite having comparable eGFR trajectories after surgery. c-AKI was significantly associated with anastomotic leakage and postoperative pneumonia [odds ratios (95%CI) 4.14 (1.30–13.18) and 3.87 (1.35–11.0), respectively]. Propensity score adjustment and inverse probability weighing yielded similar results. Mediation analysis showed that a higher incidence of anastomotic leakage in patients with c-AKI was primarily mediated by CRP levels (mediation percentage 48%). Conclusion c-AKI after preoperative chemotherapy in esophageal cancer patients was significantly associated with the development of postoperative complications and led to a resultant longer hospital stay. Increased vascular permeability and tissue edema due to prolonged inflammation might explain the mechanisms for the higher incidence of postoperative complications.

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 In gastrectomies, especially subtotal gastrectomies and operations on the gastroesophageal junction, identifying the exact location of the tumor and establishing the appropriate resection line is very important. Accurate resection lines have a major impact on the preservation of organ function and curability. Preservation of as much as possible of the remaining stomach, including the fornix, may be an important surgical goal for maintaining an adequate postoperative quality of life. In adenocarcinoma of the gastroesophageal junction, the height of the esophageal dissection may affect reconstruction of the transhiatal approach. Methods We perform a new technique, near infrared ray-guided surgery, for the accurate localization of a tumor using the Firefly technology of the daVinci Xi system and intra-operative upper gastrointestinal endoscopy. We used this new technique for cases of upper gastric cancer or adenocarcinoma of the gastroesophageal junction. In this retrospective study, we examined to determine the extent (mm) of the tumor invasion of the esophagus, visualization of near infrared ray contained within endoscopic light, and distance from the proximal margin of the tumor to the surgical cut line on rapid histopathology and in the permanent preparation, including the operative videos and extracted specimens. Results We performed near infrared ray-guided surgery for 12 patients with gastric cancer or adenocarcinoma of the gastroesophageal junction, and the near infrared ray was clearly seen as green light with Firefly mode in all the patients. Near infrared ray-guided surgery was useful for obtaining localization of the tumor. In addition, it was possible to resect organ with adequate margins from tumor. Rapid intraoperative histopathological examinations confirmed that the resected specimens had negative margins. None of the patients required additional resection. Conclusions We believe that because near infrared ray-guided surgery can provide an accurate resection line, it will be useful for the resection of upper gastric cancer and adenocarcinoma of the gastroesophageal junction. It will also provide patients with a good postoperative quality of life after surgery.

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.

The repair of DNA damage caused by chemotherapy in cancer cells occurs mainly at two cell cycle checkpoints (G

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.

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.

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.

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.

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.

Background and Objectives Although some investigators recently suggested that MMP-9 may play a critical role in invasion and metastasis, along with MMP-2, in esophageal carcinoma, there has been no direct evidence that MMPs play a critical role in the actual invasion of esophageal carcinoma cells. Here, we investigated the role of MMPs in the in vitro invasion of esophageal carcinoma cell lines (TE-series). Methods Our methods included in vitro invasion assay, gelatin zymography, and enzyme-linked immunosorbent assay (ELISA). Results Four cell lines (but not TE-5) secreted MMP-2 and MMP-9 in the culture medium. Using a quantitative in vitro invasion assay, we found a significant (P = 0.002) correlation between the extent of in vitro invasion and the amount of MMP-9, but not of MMP-2, secreted into the conditioned medium in the four cell lines. In these cell lines, R-94138, a specific MMP-9 inhibitor, inhibited in vitro invasion in a dose-dependent manner. Although TE-5 did not secrete MMP-2 or MMP-9, the cells showed a strong in vitro invasion. Conclusions Our data suggest that most of the esophageal carcinoma cell lines use MMP-9 for in vitro invasion, but others may use proteinase(s) other than MMP-9. J. Surg. Oncol. 2002;81:80–86. © 2002 Wiley-Liss, Inc.

A segment of the transverse colon can be used for gastric reconstruction after a total gastrectomy. This report presents the case of a 68-year-old woman with primary adenocarcinoma of the colon in a segment used for reconstruction after a total gastrectomy. The interposed colon developed colon carcinoma 9 years after the gastric reconstruction. The possibility of a primary carcinoma arising in a gastric colon interposition must be considered when employing the transverse colon as a gastric substitute.

With synchronously grown cells of an aerobic unicellular marine cyanobacterium Synechococcus sp. Miami BG 043511, changes in the activities of anoxygenic, nitrogenase-dependent hydrogen photoproduction and oxygen photoevolution were measured under non-growing hydrogen production conditions. Interestingly, synchronously grown cells, incubated in light under an argon atmosphere, exhibited cyclic changes in the activity of nitrogenase-catalyzed hydrogen production for approximately 20- to 25-h intervals. Cyclic photosynthetic oxygen production activity also appeared in approximately the same intervals. However, changes in hydrogen production and oxygen production activities were inversely correlated and temporally separated. Stepwise accumulation of hydrogen in closed vessels was also observed in approximately 24-h cycles in these non-growing cells. These observations in non-growing cells suggest that this unicellular aerobic, nitrogen-fixing cyanobacterium may have an endogenous system to control the exhibition of cyclic rhythms, in addition to the previously studied cell cycle-oriented system. Expression and switching between these two systems may be related to the sufficiency or insufficiency of nitrogen growth nutrients. The possibility of the existence of a common control factor of the two systems involving glycogen is also discussed.

FBXW7 is a tumor suppressor gene that induces the degradation of positive cell-cycle regulators such as c-Myc, cyclin E, c-Jun and Notch. The loss of FBXW7 promotes cell-cycle progression and cell proliferation. In the present study, we investigated the relationship between FBXW7 expression and the clinicopathological characteristics of patients with esophageal squamous cell carcinoma (ESCC). The expression of FBXW7 was quantified by real-time reverse transcription polymerase chain reaction in 43 primary ESCCs and their paired normal esophageal mucosa in patients who had not received preoperative therapy. FBXW7 expression levels were significantly correlated with the progression of the cancer and with local invasiveness. In muscle-invasive tumor cases (T2-4), lymphatic invasive tumor cases and stage II-IV cases, FBXW7 expression levels were significantly decreased (P=0.0315, P=0.0336 and P=0.0289, respectively). Decreased expression of FBXW7 was correlated with poor prognosis (P=0.0255). In conclusion, this study examined the relationship between FBXW7 expression and tumor progression in ESCC. We suggest that FBXW7 is a molecular prognostic marker and can be used to elucidate the mechanism of carcinogenesis.

Synchronously growing cells of nitrogen-fixing Synechococcus sp. Miami BG 043511 were harvested periodically and the capability for hydrogen photoproduction in closed vessels was measured under hydrogen production conditions. The capability for hydrogen photoproduction in cells was correlated with that of cellular carbohydrate content. Cells with a high carbohydrate content exhibited a high capacity for hydrogen production and those with low carbohydrate content exhibited low capacity for hydrogen production. Nitrogenase activity at the onset of incubation did not coincide with a capability for the cells to produce hydrogen during the subsequent incubation period. Interestingly, when cells with a high capacity for hydrogen photoaccumulation were incubated, alternate periods of hydrogen and oxygen accumulation were observed at 12 hour intervals. About 0.5 ml of hydrogen per ml of cell suspension was accumulated in flasks during the initial 12-h incubation period. These observations indicate that the use of synchronous culture can be one of the ways of provide materials suitable not only for basic studies but also for applied aspects of hydrogen photoproduction.

Transcription from the human immunodeficiency virus type 1 (HIV-1) provirus is activated by a cellular factor, NF kappa B, recognizing the tandemly repeated 10-base-pair sequences, termed the kappa B sequence, present in the enhancer region within the viral long terminal repeat (LTR). Using electrophoretic mobility shift assay (EMSA), which demonstrates specific DNA-protein interaction in vitro, we could demonstrate that reducto-oxidative modulation of NF kappa B dramatically changes its DNA binding activity and that a cellular physiological reducing catalyst, thioredoxin (TRX) also known as adult T cell leukemia derived factor (ADF), fully restored the DNA-binding activity of the oxidized NF kappa B. We also observed that purified TRX/ADF protein could augment gene expression from HIV LTR as demonstrated by transient chloramphenicol acetyltransferase (CAT) assay. These observations confirmed the previous notion that ADF might be an inducing factor of cellular interleukin-2 receptor alpha subunit (IL-2R alpha) through the kappa B sequence that is a common central cis-regulatory element in both IL-2R alpha and HIV gene expression. These observations indicate that reducto-oxidative regulation (or redox regulation) of a cysteine residue(s) on the NF kappa B molecule might play an important role in its specific DNA interaction and that it might provide a clue to the understanding of a pathway of cellular signal transduction to NF kappa B that is independent from the known pathways involving protein phosphorylation.

Runt-related transcription factor 3 (RUNX3) has been reported to be a candidate tumor suppressor gene in gastric cancer. However, in esophageal cancer, the role of RUNX3 has not been studied. The expression of RUNX3 mRNA was quantified by real-time reverse transcription polymerase chain reaction using Taq Man PCR in 15 esophageal cancer cell lines (TE1-15) and 70 esophageal squamous cell carcinoma (ESCC) specimens and their paired normal esophageal mucosa. The data were analyzed with reference to clinicopathological factors. Using specific primers, methylation of the promoter region of RUNX3 was examined. RUNX3 mRNA expression in ESCC tissue was significantly lower than that in the corresponding normal esophageal mucosa (3.913+/-4.617 vs. 7.795+/-15.361, P=0.0345). RUNX3 mRNA expression levels in locally invasive T4 tumors were significantly lower than those in less invasive T1-3 tumors (P=0.0454). Patients who had low RUNX3 mRNA expression levels had a significantly shorter survival after surgery compared with patients who had high RUNX3 mRNA expression (P=0.0299). Among the 15 esophageal cancer cell lines studied, one had methylation of the promoter region of RUNX3. Only 4 in 70 ESCC tumors had methylation in this region. In conclusion, RUNX3 expression may be involved in the tumor invasion and poor prognosis of patients with ESCC. The methylation of the RUNX3 promoter region in esophageal cancer is rare. A study on the mechanisms that underlie the reduced expression of RUNX3 in ESCC is warranted.

5-Fluorouracil (5-FU) is a key drug in the treatment of esophageal squamous cell carcinoma (ESCC). Gene expression of 5-FU metabolic enzymes such as thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT), has recently been investigated in order to predict the 5-FU sensitivity of several cancers. We examined the relationship between such gene expression and 5-FU sensitivity in 25 ESCC cell lines. TS, DPD, TP and OPRT mRNA levels were assessed by real-time polymerase chain reaction. The 50% inhibitory concentrations (IC50) of 5-FU in 25 ESCC cell lines were determined by cell proliferation assay. IC50 values for 5-FU ranged from 1.00 to 39.81 micromol/L. There were significant positive correlations between IC50 and TS mRNA expression (R(2) = 0.5781, P < 0.0001) and DPD mRNA expression (R(2) = 0.3573, P = 0.0016). There were no correlations between IC50 and TP or OPRT mRNA expression. TS and DPD mRNA expression levels may be useful indicators in predicting the anti-tumor activity of 5-FU in ESCC.

In this study, we examined the expression of esophageal cancer-related gene 4 (ECRG4) mRNA and evaluated its clinical significance in esophageal squamous cell carcinoma (ESCC). ECRG4 mRNA expression was quantified by real-time RT-PCR in 63 ESCC and corresponding normal esophageal mucosal samples. ECRG4 mRNA expression levels were significantly lower in ESCC tissues compared with corresponding normal esophageal mucosa (P

Caveolin-1 (CAV1) and caveolin-2 (CAV2) are the major structural proteins of caveolae. We investigated the relationship between the clinicopathological factors of esophageal squamous cell carcinoma (ESCC) and the expression of CAV1 and CAV2. CAV1 and CAV2 expression were analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 15 esophageal cancer cell lines (TE1-15) and a normal esophageal epithelium cell line (Het-1A). CAV1 and CAV2 expression was examined by RT-PCR and immunohistochemical analysis in 47 ESCC specimens. High levels of CAV1 and CAV2 mRNA were detected in TE1-15, but neither CAV1 nor CAV2 mRNA were detected in Het-1A. In the ESCC samples CAV1 and CAV2 mRNA expression in the ESCC samples were significantly higher than in the corresponding normal esophageal mucosa (CAV1, P=0.0024; CAV2, P=0.0136). However, we could not find any significant relationship between CAV1 or CAV2 mRNA expression and clinicopathological factors. Immunostaining for CAV1 was positive in 13 of 47 patients (27.7%), whereas CAV2 was positive in 22 of 47 patients (46.8%). A significant correlation was observed between CAV1 and CAV2 immunostaining and T factor, lymphatic invasion, vein invasion and differentiation. The patients with positive staining for CAV1 or CAV2 had a significantly shorter survival than those with negative staining (P=0.0105 and 0.0424 for CAV1 and CAV2, respectively). These results suggest that positive staining for CAV1 and CAV2 could be a potentially useful prognostic marker of ESCC.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly cancers in Japan. In this study we performed fluorescent in situ hybridization (FISH) and loss of heterozygosity (LOH) analysis for chromosome 18q in ESCC cells to investigate allelic imbalance of chromosome 18q in ESCC. In the FISH analysis, only one signal for chromosome 18q was detected in TE-1 esophageal cancer cells, whereas two signals were detected in TE-2 cells. Two of five resected ESCC samples from patients showed loss of one copy of chromosome 18q. To construct a precise deletion map of chromosome 18q, LOH analysis was performed using 30 microsatellite markers localized to chromosome 18q. LOH was observed in 31 of 46 ESCC samples (67.4%) for at least one locus on chromosome 18q. LOH frequency for individual markers varied from 18.5% (D18S460) to 48.4% (D18S866). Thirteen of 46 ESCC samples (28.3%) showed the loss of most of the long arm of chromosome 18. Lymph node metastasis and vein invasion were significantly associated with the deletion of chromosome 18q. Loss of chromosome 18q may play an important role in the progression of ESCC.

ACP6 (acid phosphatase 6, lysophosphatidic) is a lysophosphatidic acid (LPA)-specific phosphatase that hydrolyzes LPA to monoacylglycerol and is involved in lipid metabolism in the mitochondria. Its role in oncogenesis and cancer progression has not been studied. In this study, we examined the expression of ACP6 mRNA and evaluated its clinical significance in esophageal squamous cell carcinoma (ESCC). Expression of ACP6 mRNA was quantified by real-time reverse transcription polymerase chain reaction using the LightCycler in 70 esophageal ESCC specimens and their paired normal esophageal mucosa. The data were analyzed with reference to clinicopathological factors. ACP6 mRNA expression in esophageal cancer tissue was significantly lower than that in corresponding normal esophageal mucosa (P=0.0301). Among the esophageal cancer tissues, ACP6 mRNA expression significantly correlated with local tumor invasion (T factor, P=0.0461) and lymph node metastasis (P=0.0128). Furthermore, low ACP6 mRNA expression was associated with a significantly shorter survival time compared with high expression (log-rank test, P=0.0358). In multivariate analysis, ACP6 mRNA expression emerged as a significant independent factor (P=0.0148). Impaired ACP6 expression may lead to more aggressive invasion of ESCC, and ACP6 mRNA expression level could be an independent prognostic factor for patients with ESCC.

In some patients who already have advanced esophageal cancer at the time of presentation, symptoms like the inability to eat, and complications such as bronchoesophageal fistula are so debilitating that palliative resection may be beneficial. However, resection of the esophagus is associated with significant risk, and whether this operation should be performed for palliation remains controversial. Because few reports have been published on this subject, we retrospectively analyzed 24 patients with esophageal cancer who underwent palliative resection.Esophageal resection was performed with palliative intent in 12 patients and with curative intent in another 12 who were left with residual cancer.There was no operative death. All of the ten patients who had been unable to eat preoperatively were able to eat after the operation, and four patients with a life-threatening bronchoesophageal fistula were free of symptoms after the operation. Two patients died in hospital during the postoperative chemotherapy but the other 22 were discharged. The mean survival period was 264 days.With improved postoperative care, the risk of palliative esophageal resection is no longer considered unacceptable.

Background and Objectives Telomerase has been suggested as being necessary for continued cell growth and progression of cancer. Esophageal cancer and matched normal esophageal tissue from 54 patients were analyzed for telomerase activity, human telomerase reverse transcriptase (hTERT) mRNA expression, and their correlation with clinicopathological factors. Methods Telomeric repeat amplification protocol was used for detection of telomerase activity and real time quantitative RT-PCR was used for hTERT mRNA. An esophageal carcinoma cell line was used to study the effect of chemotherapeutic agent on telomerase. Results Telomerase activity was detectable in 79.6% of the tumor and 59.3% of the normal esophageal tissue. The level of telomerase activity in the tumor was significantly higher than that in the normal tissue. A significantly higher telomerase activity was observed in tumors with extensive blood vessel invasion. A significantly lower telomerase activity was observed in tumors that showed good response to preoperative chemotherapy than those with poor response. TE-9 cells exposed to 5-FU showed a diminished telomerase activity preceded by a time-dependent decrease in the mRNA expression of hTERT. Conclusions Telomerase activity was high in esophageal cancer tissue and showed positive correlation with blood vessel invasion. Chemotherapeutic agents may down-regulate telomerase activity. J. Surg. Oncol. 2002;79:37–45. © 2002 Wiley-Liss, Inc.

Esophageal squamous cell carcinoma (ESCC) is a common and highly fatal cancer in Japan. Systemic chemotherapy is used, but some tumors show resistance to it. The mechanisms of tumor resistance to chemotherapy remain largely unknown. We determined the chemosensitivity of 15 ESCC cell lines (TE-1-5, TE-8-15, KYSE140 and KYSE150) to docetaxel by clonogenic and MTT assays. We used cDNA microarray analysis and quantitative RT-PCR to determine which genes might determine resistance to docetaxel. Small interfering RNA (siRNA) was used to suppress gene expression and its effect on the chemosensitivity of the cell was determined. The cell line with the most resistance to docetaxel was TE-2. Using microarray analysis, we identified beta1 integrin (ITGB1) to be overexpressed in this cell line. Higher expression of ITGB1 mRNA was significantly associated with docetaxel resistance (n=15, r2=0.66, P=0.0110). Suppression of ITGB1 expression using siRNA sensitized the TE-2 cells to docetaxel. These data suggest that overexpression of ITGB1 may be related to resistance to chemotherapy and that targeting ITGB1, particularly in patients on docetaxel therapy, may enhance the effect of chemotherapy in patients with ESCC.

The aerobic synchronous growth of marine unicellular cyanobacteriaSynechococcus spp., with molecular nitrogen as the sole nitrogen growth nutrient source, was experimentally demonstrated. Cell division synchrony was induced by withholding aeration and illumination for 20 h. Three distinct cell division cycles of approximately 20 h each were observed. During the first cell division cycle, high degrees of synchrony of 78%–86% were observed in the series of cultures studied. The aerobic nitrogenase activity appeared shortly while the cell division was completed and the cell size was still small, and it disappeared after the cells were enlarging photosynthetically. Thus, three distinct cycles in aerobic nitrogenase activity were also observed having approximately the same 20-h interval as the cell division cycle. The peak aerobic nitrogenase activity was determined to be as high as 840–1220 nmol C2H2 reduced per milligram dry weight per hour.

A marine unicellular aerobic nitrogen-fixing cyanobacterium Synechococcus sp. strain Miarni BG 043511 was pretreated with different light and dark regimes in order to induce higher growth synchrony. A pretreatment of two dark and light cycles of 16 h each yielded good synchrony for 3 cell division cycles. Longer dark treatments decreased the degree of synchrony and shorter dark treatments caused irregular cell division. Once synchronous culture was established, distinct phases of cellular carbohydrate accumulation and cellular carbohydrate degradation were observed even under continuous illumination. Changes in carbohydrate content were repeated in a cyclic manner with approximately 20 h intervals, the same as the cell division cycle. This change in carbohydrate metabolism provided a good index of growth synchrony under nitrogen-fixing conditions. Photosynthetic oxygen evolution and nitrogen fixation capabilities and their activities in near, in situ, culture conditions were measured in well synchronized cultures of this strain under continuous illumination. Distinct oscillations of both photosynthetic oxygen evolution and nitrogen fixation capabilities with ca 20-h intervals, similar to the interval of the cell division cycle, were observed for three cycles. However, the activities of photosynthetic oxygen evolution were inversely correlated with those of nitrogen fixation. During the nitrogen fixation period, net oxygen consumption was observed even in the light under conditions approximating in situ culture conditions. The phase of temporal appearance of nitrogenase activity during the cell division cycle coincided with the phase of carbohydrate net degradation. These data indicate that this unicellular cyanobacterium can grow diazotrophically under conditions of continuous illumination by the segregation of photosynthesis and nitrogen fixation within a cell division cycle.

Ferredoxin isolated from a blue-green alga, Nostoc sp., was purified and crystallized. The absorption spectrum of Nostoc ferredoxin had, in the oxidized state, peaks at 276, 331, 423, and 470 nm, a pattern characteristic of chloroplast-type ferredoxin. The 423:276 absorption ratio was 0.57. The midpoint oxidation-reduction potential of Nostoc ferredoxin was found to be –406 mV, at pH 7.5. Nostoc ferredoxin mediated the photoreduction of NADP by isolated Nostoc chromato-phores and spinach chloroplasts from which the native ferredoxin was removed. The molar ratio of Nostoc ferredoxin to chlorophyll a was about 1:50, a ratio higher than usually found in photosynthetic cells. The possible evolutionary significance of the properties of Nostoc ferredoxin compared with those of ferredoxins from other photosynthetic organisms is discussed.

Purine nucleoside phosphorylase (purine nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) has been purified 125-fold from the homogenate of chicken livers and some of the properties of the purified enzyme have been studied. This enzyme had a pH optimum at around 6.o. At high substrate levels of inosine the reaction rate was increased, suggesting that substrate activation of the enzyme had occurred. The enzyme activity was completely lost after 48 h at −20°. The inhibition by nucleotides and SO 4 2− is a characteristic of this enzyme and has not been previously reported.

1. 1.|5′-Nucleotidase (5′-ribonucleotide phosphophydrolase, EC 3.1.3.5) was partially purified from chicken liver. This is the first time it has been possible to obtain 5′-nucleotidase from the hepatic tissue of uricotelic animals and it was found to be kinetically distinct from 5′-nucleotidases obtained from other sources. 2. 2.|5′-Mononucleotides having a keto group at position 6 in the purine base are the most active substrates of this enzyme. 5′-IMP is the most active substrate among the 5′-nucleotides tested, and it is about 10 times more active than 5′-AMP. 3. 3.|This enzyme has an optimum pH at 6.5 and requires divalent metal ions. In the absence of divalent metal ions, the enzyme is almost inactive. 4. 4.|Inosino, guanosine p-chloromercuribenzoate (PCMB) and NaF inhibit this enzyme. Of these inhibitors, PCMB was found to be the most potent. 5. 5.|The general properties of the enzyme are described, and its possible metabolic function is discussed.