Application and outcomes of a standardized lymphadenectomy in laparoscopic right hemicolectomy requiring ligation of the middle colic artery.

BACKGROUND: Complete mesocolic excision with central vessel ligation may be important for accurate staging and improving the prognosis of right-sided colon cancer. Although the procedure is often performed laparoscopically, approaching the middle colic artery (MCA) is technically demanding, especially when complete ligation of arteries at their roots is desired. We standardized our laparoscopic approach by establishing the dissection boundary along the superior mesenteric artery to achieve D3 lymphadenectomy in the region of the MCA. The aim of the present study was to evaluate, on the basis of perioperative and short-term oncologic outcomes, the feasibility and safety of our technique METHODS: We conducted a retrospective study on consecutive patients with cancer located at the ascending colon and transverse colon who had laparoscopic right hemicolectomy requiring ligation of the MCA. RESULTS: There were 41 patients (22 males, median age 71 years [range 49-86] years). The median operation time was 285 min, and blood loss volume was 40 mL. Conversion to open surgery was required in 1 case. Complications that were Clavien-Dindo grade III or above occurred in 3 patients (7.3%). There was no anastomotic leakage. The median number of lymph nodes harvested was 46. CONCLUSIONS: Our technique was shown to be a safe, feasible, and useful strategy for performance of right hemicolectomy requiring ligation of the MCA in cases of colon cancer. The technique facilitates maximal lymph node dissection. Having obtained favorable outcomes, we look forward to investigation into long-term outcomes.

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer.

BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

Evaluation of the Glasgow Prognostic Score in patients receiving chemoradiotherapy for stage III and IV esophageal cancer.

High Glasgow Prognostic scores (GPSs) have been associated with poor outcomes in various tumors, but the values of GPS and modified GPS (mGPS) in patients with advanced esophageal cancer receiving chemoradiotherapy (CRT) has not yet been reported. We have evaluated these with respect to predicting responsiveness to CRT and long-term survival. Between January 2002 and December 2011, tumor responses in 142 esophageal cancer patients (131 men and 11 women) with stage III (A, B and C) and IV receiving CRT were assessed. We assessed the value of the GPS as a predictor of a response to definitive CRT and also as a prognostic indicator in patients with esophageal cancer receiving CRT. We found that independent predictors of CRT responsiveness were Eastern Cooperative Oncology Group (ECOG) performance status, GPS and cTNM stage. Independent prognostic factors were ECOG performance status and GPS for progression-free survival and ECOG performance status, GPS and cTNM stage IV for disease-specific survival. GPS may be a novel predictor of CRT responsiveness and a prognostic indicator for progression-free and disease-specific survival in patients with advanced esophageal cancer. However, a multicenter study as same regime with large number of patients will be needed to confirm these outcomes.

Eagle's syndrome-A non-perceived differential diagnosis of temporomandibular disorder.

INTRODUCTION: This article unveils a case of the classic styloid syndrome and states that panoramic imaging and ultrasound can be an alternative to computed tomography. In addition, the endoscope-assisted extraoral approach using CT-based navigation is useful. Eagle's Syndrome is an aggregate of symptoms described by Eagle in 1937. He described different forms: the classic styloid syndrome consisting of elongation of the styloid process which causes pain. Second, the stylo-carotid-artery syndrome which is responsible for transient ischemic attack or stroke. PRESENTATION OF CASE: Using the example of a 66 years old male patient suffering from long term pain, we explain our diagnostic and surgical approach. After dissecting the styloid process of the right side using an extraoral approach, the pain ceased and the patient could be discharged without any recurrence of the pain up to this point. DISCUSSION: Eagle's syndrome, with its similar symptoms, is rather difficult to differentiate from temporomandibular joint disorders (TMD), but can be easily excluded from possible differential diagnoses of TMD using panoramic radiographs and ultrasound. CONCLUSION: Making use of low cost and easily accessible diagnostic workup techniques can reveal this particular cause for chronic pain restricting quality of life. Thereby differentiation from the TMD symptomatic complex is possible.

In vivo comparison of hard tissue regeneration with ovine mesenchymal stem cells processed with either the FICOLL method or the BMAC method.

INTRODUCTION: The aim of this work was to analyse the suitability of mesenchymal stem cell isolation by FICOLL density centrifugation and the closed bone marrow aspirate concentrate (BMAC) system for sinus augmentation with bovine bone mineral (BBM) in the sheep model. METHODS: 16 sheep underwent sinus augmentation with BBM and MSCs; they were divided between two groups with survival points of 8 and 16 weeks. For the FICOLL control arm three, and for the BMAC test arm, five augmentations were performed for each time point. The derived cell numbers were counted; a colony forming unit (CFU) assay was performed; the pluripotency of the MSCs was proved; histological and histomorphometrical analysis were performed. RESULTS: The approach of using BBM and MSCs in combination with fibrin adhesive was sufficient for new bone formation as the FICOLL experiment indicated. However, due to significantly lower cell numbers isolated using the BMAC in sheep, less new bone was formed in the test arm. CONCLUSIONS: The BMAC system is well suited for human MSC isolation but it needs to be optimized to fit sheep cell characteristics if it is to be used in this animal model.

A New Statistical Model Identified Two-thirds of Clinical T1 Gastric Cancers as Possible Candidates for Endoscopic Treatment.

BACKGROUND: Clinical T1 gastric cancer has low metastatic potential to lymph nodes and is generally curable by local treatment. Endoscopic resection can preserve the whole stomach and does not impair the patient's quality of life; however, its indication is strictly limited to the subset of patients without nodal metastasis. The study was designed to predict reliably the patients without nodal metastasis based only on the clinical information. METHODS: We examined patients with clinical T1 disease who were treated with surgery. The clinically available information was evaluated for its ability to predict nodal metastasis by logistic regression model. Then, the predictive ability of the logistic regression model using the risk factors for nodal metastasis was evaluated by a receiver operating characteristic curve. RESULTS: A total of 511 patients were entered into this study. The clinical depth (cT1a or cT1b), maximal tumor diameter, and pathological type were confirmed to be significantly different between patients with and without nodal metastasis. The cutoff value of the tumor diameter differed depending on the histology and clinical depth: 79 mm for differentiated type and 48 mm for undifferentiated type in cT1a tumors, and 43 mm for differentiated type and 11 mm for undifferentiated type in cT1b tumors. According to these criteria, 348 of the 511 patients (68.1 %) were classified to have predictive N0 status. The negative predictive value was 95.7 % (95 % confidence interval 94.0-97.5 %). CONCLUSIONS: The predictive criteria based on the multivariate logistic model identified that almost two-thirds of the patients with clinical T1 gastric cancer were possible candidates for endoscopic treatment.

Prognostic significance of CD44 variant 2 upregulation in colorectal cancer.

BACKGROUND: CD133 and CD44 are putative cancer stem cell (CSC) markers in colorectal cancer (CRC). However, their clinical significance is currently unclear. Here, we evaluated primary CRC cell isolates to determine the significance of several CSC markers, including CD133 and CD44, as predictors of tumourigenesis and prognosis. METHODS: CD133- and CD44-positive cells from fresh clinical samples of 77 CRCs were selected by flow cytometric sorting and evaluated for tumourigenicity following subcutaneous transplantation into NOD/SCID mice. Cancer stem cell marker expression was examined in both xenografts and a complementary DNA library compiled from 167 CRC patient samples. RESULTS: CD44(+), CD133(+) and CD133(+)CD44(+) sub-populations were significantly more tumourigenic than the total cell population. The clinical samples expressed several transcript variants of CD44. Variant 2 was specifically overexpressed in both primary tumours and xenografts in comparison with the normal mucosa. A prognostic assay using qRT-PCR showed that the CD44v2(high) group (n=84, 5-year survival rate (5-OS): 0.74) had a significantly worse prognosis (P=0.041) than the CD44v2(low) group (n=83, 5-OS: 0.88). CONCLUSIONS: CD44 is an important CSC marker in CRC patients. Furthermore, CRC patients with high expression of CD44v2 have a poorer prognosis than patients with other CD44 variants.

IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling.

BACKGROUND: Interleukin-22 (IL-22) has been recently highlighted owing to its biological significance in the modulation of tissue responses during inflammation. However, the role of IL-22 in carcinogenesis has remained unclear. Here, we investigated the pathophysiological significance of IL-22 expression in gastric cancer tissues and examined the mechanism by which IL-22 promotes gastric cancer cell invasion. METHODS: Human gastric cancer specimens were analysed by immunohistochemistry for expression of IL-22 and IL-22 receptor 1 (IL-22R1). The effects of IL-22-induced STAT3 and ERK signalling on invasive ability of gastric cancer cells were examined using a small-interfering RNA system and specific inhibitors. AGS cells were co-cultured with cancer-associated fibroblasts (CAFs) from human gastric cancer tissues and assessed by invasion assay. RESULTS: Interleukin-22 and its receptor were expressed in α-smooth muscle actin-positive stromal cells and tumour cells at the invasive front of gastric cancer tissues, respectively. The expression of IL-22 and IL-22R1 was significantly related to lymphatic invasion. Interleukin-22 treatment promoted the invasive ability of gastric cancer cells through STAT3 and ERK activation. The invasive ability of gastric cancer cells was significantly enhanced by co-culture with IL-22-expressing CAFs. CONCLUSIONS: Interleukin-22 produced by CAFs promotes gastric cancer cell invasion via STAT3 and ERK signalling.

Effect of rikkunshito on the expression of substance P and CGRP in dorsal root ganglion neurons and voluntary movement in rats with experimental reflux esophagitis.

BACKGROUND: While there are reports that the herbal medicine rikkunshito (RKT) relieves upper gastrointestinal disease symptoms, the effect of RKT on primary afferent neurons is unknown. METHODS: A model of reflux esophagitis (RE) was implemented using male Wistar rats aged 6-7 weeks. Ten days after surgery, the total area of esophageal mucosal erosion sites was determined. Th8-10 dorsal root ganglia (DRG) were dissected out and the expression of substance P (SP), calcitonin gene-related peptide (CGRP), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was determined in DRG using immunohistochemistry. RKT (0.6%/WV) or omeprazole (OME) (10 mg/kg) was administered for 10 days beginning on the day after surgery. Voluntary movement was measured with an infrared sensor for 22 h each day. KEY RESULTS: RE rats showed esophageal mucosal erosion and significantly increased number of SP/CGRP- and p-ERK1/2-immunoreactive neurons in DRG. Treatment with OME improved the size of erosive lesions in the esophageal mucosa of RE rats, while RKT did not. Treatment with RKT or OME significantly reduced the expression of SP/CGRP and p-ERK1/2 in DRG, and significantly increased voluntary movement in RE rats. CONCLUSIONS & INFERENCES: RKT inhibited the activation of ERK1/2 and decreased the expression of SP and CGRP in DRG of RE rats, which may be associated with the observed amelioration of voluntary movement.

Diagnostic value of computed tomography for staging of clinical T1 gastric cancer.

BACKGROUND: T1 gastric cancer can be diagnosed only by endoscopy and is almost curable by local treatment. It has been unclear how a multidetector-row computed tomography (CT) evaluation is valuable for clinical T1 patients. METHODS: Patients with clinical T1 disease, as diagnosed by endoscopy and treated with endoscopic submucosal dissection (ESD) or surgery between October 2000 and October 2007, were examined. The efficacy of CT was evaluated by the reversal rate of endoscopic T1 by CT, the incidence of clinical M1 disease, and the accuracy of diagnosing pathological N+ disease in patients who received surgery. To confirm metachronous distant and nodal metastases, the disease-free survival (DFS) also was evaluated. RESULTS: A total of 761 patients, 236 treated by ESD and 525 treated with surgery, were examined. None of the patients had an endoscopic diagnosis of clinical T1 reversed by CT. No clinical M1 disease was found. Among the 525 patients who underwent surgery, 8 showed clinical N+ disease (1.5 %), while 47 demonstrated pathological N+ disease (8.9 %). The accuracy, sensitivity, specificity, positive predictive value, and negative predictive values were 90.3, 4.3, 98.7, 25, and 91.3 %, respectively. The 5-year DFS rate was 93.6 % (95 % confidence interval 91.4-95.8 %). CONCLUSIONS: The present study suggests that diagnostic value of CT is limited for staging of clinical T1 gastric cancer patients, because the reversal rate of endoscopic T1 by CT was very low, clinical M1 disease was rare, the diagnosis of N+ status was unreliable, and metachronous M1 and N+ findings were rare.

Global histone modification of H3K27 correlates with the outcomes in patients with metachronous liver metastasis of colorectal cancer.

BACKGROUND: We evaluated the methylation patterns of histone H3 lysine 27 (H3K27), H3 lysine 36 (H3K36) and the expression of H3K27 methylase EZH2 in patients with colorectal carcinomas with metachronous liver metastasis to search for biomarkers identifying these patients. METHODS: Double 2-mm core tissue microarrays were made from 54 paraffin-embedded samples of primary colorectal adenocarcinomas and corresponding liver metastases and examined using an immunohistochemical analysis of dimethylation and trimethylation in H3K27, H3K36 and EZH2. Positive tumor cell staining for each histone modification (H-score) was used to classify patients into low- and high-staining groups, which were then examined to identify any correlations between the clinicopathological parameters and the clinical outcomes. RESULTS: The H-scores of H3K27me2 were lower in the liver metastases than in the corresponding primary tumors, while the H-scores of H3K36me2 were higher in the liver metastases than in the corresponding primary tumors (P < 0.001). H3K27me2 in the primary tumors correlated with tumor size (P = 0.016), H3K36me2 in the primary tumors correlated with histological type (P = 0.038), and H3K36me3 in the primary tumors correlated with lymph node metastasis (P = 0.017). In addition, lower levels of H3K27me2 in the primary tumors correlated with poorer survival rates (P = 0.039). The multivariate survival analysis showed that the H3K27me2 status is an independent prognostic factor for colorectal cancer patients (P = 0.047). CONCLUSIONS: Our findings suggest that the methylation level of H3K27me2 detected with immunohistochemistry may be an independent prognostic factor for metachronous liver metastasis of colorectal carcinomas.

Chronic rhinosinusitis in ex-lepromatous leprosy patients with atrophic rhinitis.

AIM: Rhino-sinus mucosal involvement is well documented in untreated lepromatous leprosy, but less understood in ex-leprosy patients (i.e. leprosy patients who have been treated and cured) with atrophic rhinitis. MATERIALS AND METHODS: Rhino-sinus abnormalities were investigated in 13 ex-lepromatous leprosy patients with atrophic rhinitis, using interviews enquiring about sinonasal symptoms, nasal endoscopy, nasal swab culture and computed tomography. Endoscopic sinus surgery had been performed in three patients. The clinical course, computed tomography findings and nasal biopsy results of these three patients were evaluated. RESULTS: All patients had turbinate atrophy and 6 of the 13 (46.2 per cent) had septal perforation. Paranasal sinus involvement was noted in 9 of 12 examined patients (75 per cent). The most commonly affected sinus was the maxillary sinus (in 8 of 12; 66.7 per cent). All three patients treated by endoscopic sinus surgery experienced relapse and required further surgery. Maxillary sinus irrigation was effective for reduction of persistent symptoms such as postnasal discharge and crusts. CONCLUSION: Ex-lepromatous leprosy patients with atrophic rhinitis had various rhino-sinus abnormalities and persistent symptoms. These patients had chronic rhinosinusitis because of underlying atrophic rhinitis. These patients required repeated otolaryngological observations together with combined surgery and conservative treatment.

REG Iα is a biomarker for predicting response to chemotherapy with S-1 plus cisplatin in patients with unresectable stage IV gastric cancer.

BACKGROUND: The regenerating gene Iα (REG Iα) is involved in gastric carcinogenesis as an antiapoptotic factor. Therefore, we investigated whether REG Iα confers resistance to chemotherapeutic drugs in gastric cancer (GC) cells and whether REG Iα expression is useful for predicting the response to chemotherapy and outcome in patients with GC. METHODS: A total of 70 patients with unresectable stage IV GC received first-line chemotherapy with S-1 and cisplatin (S-1/CDDP). The expression of REG Iα was evaluated immunohistochemically using biopsy samples obtained before chemotherapy, and its relationship to clinicopathological parameters was analysed statistically. The effects of REG Iα gene induction on resistance to 5-FU or CDDP treatment were examined by cell survival assay and flow cytometry. RESULTS: Of the 70 patients with unresectable stage IV GC, 19 (27%) were positive for REG Iα expression. The expression of REG Iα was independently predictive of poorer progression-free and overall survival in such patients (hazard ratio (HR) 2.46; P=0.002 and HR 1.89; P=0.037, respectively). The gene induction of REG Iα conferred resistance to cell death induced by 5-FU or CDDP in GC cells. CONCLUSION: In patients with stage IV GC, REG Iα, which confers resistance to chemotherapeutic drugs in GC cells, is a potential biomarker for predicting resistance to S-1/CDDP treatment.

NK-1 receptor is involved in the decreased movement in a rat chronic acid reflux oesophagitis model.

BACKGROUND: We previously reported that rats with reflux oesophagitis (RE) show a decrease in voluntary movement, which could be used as a measure of chronic visceral symptoms. However, what mediates these symptoms is still unknown, and pain-related neuropeptides or their receptors in oesophageal mucosa are possibly related to the symptom generation of oesophagitis. In the present study, we investigated the role of NK-1 receptor (NK-1R) as a mediator of oesophagitis symptoms. METHODS: Chronic RE was surgically induced using rats. The degree or severity of oesophageal symptoms was evaluated by assessing voluntary movement, which was monitored using an infrared sensor system. The NK-1R antagonist, L-732,138, was administered and changes in voluntary movement were assessed. Ten days after surgery, the rats were killed to examine the oesophagus. NK-1R and tachykinin-1 mRNA were detected by real-time RT-PCR. NK-1R protein expression was examined by Western blotting. KEY RESULTS: Voluntary movement of the oesophagitis model rats was significantly lower than that of the sham-operated rats on day 10. The size of oesophageal mucosal erosion did not correlate with the amount of voluntary movement. The amount of NK-1R protein and mRNA in the oesophageal tissue was significantly higher at both the erosion and non-erosion sites. The amount of tachykinin-1 mRNA in oesophageal tissue at the non-erosion sites was significantly higher in oesophagitis rats. The voluntary movement of oesophagitis rats was significantly increased by the administration of L-732,138. CONCLUSIONS & INFERENCES: The NK-1R and related neuropeptides are possibly involved in the decrease in voluntary movement of RE.

An experimental attenuation plate to improve the dose distribution in intraoperative electron beam radiotherapy for breast cancer.

Intraoperative electron beam radiotherapy (IOERT) is a technique in which a single-fraction high dose is intraoperatively delivered to subclinical tumour cells using an electron beam after breast-conserving surgery. In IOERT, an attenuation plate consisting of a pair of metal disks is commonly used to protect the normal tissues posterior to the breast. However, the dose in front of the plate is affected by backscatter, resulting in an unpredictable delivered dose to the tumour cells. In this study, an experimental attenuation plate, termed a shielding plate, was designed using Monte Carlo simulation, which significantly diminished the electron beam without introducing any backscatter radiation. The plate's performance was verified by measurements. It was made of two layers, a first layer (source side) of polymethyl methacrylate (PMMA) and a second layer of copper, which was selected from among other metals (aluminium, copper and lead) after testing for shielding capability and the range and magnitude of backscatter. The optimal thicknesses of the PMMA (0.71 cm) and copper (0.3 cm) layers were determined by changing their thicknesses during simulations. On the basis of these results, a shielding plate was prototyped and depth doses with and without the plate were measured by radiophotoluminescence glass dosimeters using a conventional stationary linear accelerator and a mobile linear accelerator dedicated for IOERT. The trial shielding plate functioned as intended, indicating its applicability in clinical practice.

Interobserver agreement in endoscopic evaluation of reflux esophagitis using a modified Los Angeles classification incorporating grades N and M: a validation study in a cohort of Japanese endoscopists.

The Los Angeles classification system is the most widely employed criteria associated with the greatest interobserver agreement among endoscopists. In Japan, the Los Angeles classification system has been modified (modified LA system) to include minimal changes as a distinct grade of reflux esophagitis, rather than as auxiliary findings. This adds a further grading M defined as minimal changes to the mucosa, such as erythema and/or whitish turbidity. The modified LA system has come to be used widely in Japan. However, there have been few reports to date that have evaluated the interobserver agreement in diagnosis when using the modified LA classification system incorporating these minimal changes as an additional grade. A total of 100 endoscopists from university hospitals and community hospitals, as well as private practices in the Osaka-Kobe area participated in the study. A total of 30 video clips of 30-40 seconds duration, mostly showing the esophagocardiac junction, were created and shown to 100 endoscopists using a video projector. The participating endoscopists completed a questionnaire regarding their clinical experience and rated the reflux esophagitis as shown in the video clips using the modified LA classification system. Agreement was assessed employing kappa (kappa) statistics for multiple raters. The kappa-value for all 91 endoscopists was 0.094, with a standard error of 0.002, indicating poor interobserver agreement. The endoscopists showed the best agreement on diagnosing grade A esophagitis (0.167), and the poorest agreement when diagnosing grade M esophagitis (0.033). The kappa-values for the diagnoses of grades N, M, and A esophagitis on identical video pairs were 0.275-0.315, with a standard error of 0.083-0.091, indicating fair intraobserver reproducibility among the endoscopists. The study results consistently indicate poor agreement regarding diagnoses as well as fair reproducibility of these diagnoses by endoscopists using the modified LA classification system, regardless of age, type of practice, past endoscopic experience, or current workload. However, grade M reflux esophagitis may not necessarily be irrelevant, as it may suggest an early form of reflux disease or an entirely new form of reflux esophagitis. Further research is required to elucidate the pathophysiological basis of minimal change esophagitis.

Wip1 protects hydrogen peroxide-induced colonic epithelial barrier dysfunction.

Tight junctions (TJs) create a paracellular permeability barrier. Although reactive oxygen species have been implicated as mediators of inflammation in inflammatory bowel diseases, their influence on the function of colonic epithelial TJs remains unknown. Oxidative stress-mediated colonic epithelial permeability was significantly attenuated by a p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Although the amount of TJ proteins was not altered, hydrogen peroxide (H2O2) changed the localization of claudin-4 protein from an NP-40 insoluble fraction to a soluble fraction and from an apical TJ to lateral membrane. The p38 MAP kinase inactivator Wip1 significantly attenuated phosphorylation of p38 MAP kinase, and oxidative stress mediated permeability. H2O2-induced changes in claudin-4 localization were abolished by SB203580 pretreatment as well as Wip1-expressing adenovirus infection. This is the first study to demonstrate that exogenous Wip1 functions to protect oxidative stress-mediated colonic mucosal permeability and that H2O2-induced claudin-4 dislocalization is abolished by Wip1.

Endoscopic submucosal dissection: a safe technique for colorectal tumors.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) aims to resect large neoplastic lesions en bloc, allowing for more precise histopathological analysis. The present retrospective study aimed to analyze the technical and clinical outcomes after ESD of colorectal tumors. PATIENTS AND METHODS: ESD was performed for the treatment of 71 colorectal neoplasms in 70 patients (38 men, 32 women; mean age 63.4 years). Lesion size, procedure time, complications, and immediate and follow-up outcomes were evaluated. The results for these 71 lesions were compared with those for a group of 32 lesions treated by conventional piecemeal endoscopic mucosal resection (EMR) performed during the same period. RESULTS: For the ESD-treated group of lesions, the average lesion size was 32.7 mm (range 13-80 mm), and the mean operating time was 61.1 minutes (range 7-164 minutes). One perforation occurred in the ESD group (1.4%) and this was treated conservatively with clipping. The majority of these lesions (n = 50) were laterally spreading tumors. Histological examination showed low-grade adenoma in 12 cases; high-grade intraepithelial neoplasia in 47 cases; and submucosally invasive cancer in 11 cases, of which four were sm1, and seven were sm2 or sm3 (these seven patients underwent surgery). The en bloc resection rate was 98.6%. For the 64 tumors that were treated by radical endoscopic resection, no tumor recurrence was found after a mean follow-up period of 12.2 months (range 3-34 months) and a mean of 2.1 follow-up endoscopies (range 1-4). This contrasted with the 6.3% recurrence rate in the 32 piecemeal EMR cases (mean tumor size 28.7 mm, range 20-60 mm). CONCLUSION: In our hands, ESD is a safe and effective resection technique for large colorectal neoplasms. As experience with the technique increases, it might gradually replace piecemeal EMR in the majority of cases.

Unique polyamines produced by an extreme thermophile, Thermus thermophilus.

Recent research progress on polyamines in extreme thermophiles is reviewed. Extreme thermophiles produce two types of unique polyamines; one is longer polyamines such as caldopentamine and caldohexamine, and the other is branched polyamines such as tetrakis(3-aminopropyl)ammonium. The protein synthesis catalyzed by a cell-free extract of Thermus thermophilus, an extreme thermophile, required the presence of a polyamine and the highest activity was found in the presence of tetrakis(3-aminopropyl)ammonium. In vitro experiments, longer polyamines efficiently stabilized double stranded nucleic acids and a branched polyamine, tetrakis(3-aminropyl)ammonium, stabilized stem-and-loop structures. In T. thermophilus, polyamines are synthesized from arginine by a new metabolic pathway; arginine is converted to agmatine and then agmatine is aminopropylated to N(1)-aminopropylagmatine which is converted to spermidine by an enzyme coded by a gene homologous to speB (a gene for agmatinase). In this new pathway spermidine is not synthesized from putrescine. Reverse genetic studies indicated that the unique polyamines are synthesized from spermidine.