Risk factors associated with multiple and missed gastric neoplastic lesions after endoscopic resection: prospective study at a single institution in south Korea.

BACKGROUND/AIMS: Only a small part of visible gas tric mucosal lesion can be removed by endoscopic resection. This study is aimed to identify incidence rate and associated risk factors of multiple and missed gastric lesions, and proper timing of follow-up en doscopy. METHODOLOGY: Endoscopic surveillance was performed on 1 week, and 1, 6, 12 months af ter endoscopic resection. All multiple gastric lesions were divided into main and accessory lesions. The accessory lesions were subdivided into detected and missed lesions. RESULTS: Totally, 250 lesions of 215 patients were analyzed. There were 81 early gastric cancers, 50 high grade dysplasias and 119 low grade dysplasias. Thirty patients (14%) had multiple gastric neoplastic lesions, either adenoma or cancer, within 1 year follow-up after endoscopic resection. Old age, male gender and severe intestinal metaplasia were independent risk factors of multiple gastric lesions. Small size (≤ 1 cm) and flat morphology were major risk factors of missed lesion. Among 10 missed lesions, 9 (90%) could be detected within 6 month after resection. CONCLUSIONS: Old age, male gender, severe intestinal metaplasia were risk factors for multiple gastric lesions after endoscopic resection. Follow-up endoscopy is needed at least one time within six months after resection, with careful inspection of entire stomach.

Comparative enzyme inhibitive methanol production by Methylosinus sporium from simulated biogas.

Methane in a simulated biogas converting to methanol under aerobic condition was comparatively assessed by inhibiting the activity of methanol dehydrogenase (MDH) of Methylosinus sporium using phosphate, NaCl, NH4Cl or EDTA in their varying concentrations. The highest amount of methane was indistinguishably diverted at the typical conditions regardless of the types of inhibitors: 35°C and pH 7 under a 0.4% (v/v) of biogas, specifically for <40 mM phosphate, 50 mM NaCl, 40 mM NH4Cl or 150 µM EDTA. The highest level of methanol was obtained for the addition of 40 mM phosphate, 100 mM NaCl, 40 mM NH4Cl or 50 µM EDTA. In other words, 0.71, 0.60, 0.66 and 0.66 mmol methanol was correspondingly generated by the oxidation of 1.3, 0.67, 0.74 and 1.3 mmol methane. It gave a methanol conversion rate of 54.7%, 89.9%, 89.6% and 47.8%, respectively. Among them, the maximum rate of methanol production was observed at 6.25 µmol/mg h for 100 mM NaCl. Regardless of types or concentrations of inhibitors differently used, methanol production could be nonetheless identically maximized when the MDH activity was limitedly hampered by up to 35%.

Partial oxidative conversion of methane to methanol through selective inhibition of methanol dehydrogenase in methanotrophic consortium from landfill cover soil.

Using a methanotrophic consortium (that includes Methylosinus sporium NCIMB 11126, Methylosinus trichosporium OB3b, and Methylococcus capsulatus Bath) isolated from a landfill site, the potential for partial oxidation of methane into methanol through selective inhibition of methanol dehydrogenase (MDH) over soluble methane monooxygenase (sMMO) with some selected MDH inhibitors at varied concentration range, was evaluated in batch serum bottle and bioreactor experiments. Our result suggests that MDH activity could effectively be inhibited either at 40 mM of phosphate, 100 mM of NaCl, 40 mM of NH4Cl or 50 µM of EDTA with conversion ratios (moles of CH3OH produced per mole CH4 consumed) of 58, 80, 80, and 43 %, respectively. The difference between extent of inhibition in MDH activity and sMMO activity was significantly correlated (n = 6, p < 0.05) with resultant methane to methanol conversion ratio. In bioreactor study with 100 mM of NaCl, a maximum specific methanol production rate of 9 µmol/mg h was detected. A further insight with qPCR analysis of MDH and sMMO coding genes revealed that the gene copy number continued to increase along with biomass during reactor operation irrespective of presence or absence of inhibitor, and differential inhibition among two enzymes was rather the key for methanol production.

Efficacy and safety of 0.4 percent sodium hyaluronate for endoscopic submucosal dissection of gastric neoplasms.

AIM: To evaluate the efficacy and safety of sodium hyaluronate solution (SH) in endoscopic submucosal dissection (ESD) of gastric neoplasms. METHODS: A prospective multicenter randomized, double blind, controlled trial was designed and utilized in this study. A total of 76 patients with 5-20 mm sized gastric neoplasms were enrolled at three academic hospitals in South Korea from June 2011 to October 2011. Patients were randomly assigned to the 0.4% sodium hyaluronate or control groups. All lesions underwent endoscopic ESD. ESD was performed with 0.4%SH and normal saline (NS) solution for submucosal injection. Efficacy was assessed using en bloc resection and the number of additional injections. Secondary evaluation variables were the volume of injection material, steepness of mucosal elevation, bleeding rate, procedural time and operator satisfaction. Finally, the safety was assessed by analyzing adverse events during the study. RESULTS: The usefulness rate in the 0.4%SH group and the controlled group had statistically significant difference under intention to treat (ITT) analysis (90.91% vs 61.11% P = 0.0041). Under per protocol (PP), the usefulness rate is statistically significant different (93.10% vs 61.76%, P = 0.0036). The difference in volume of the solution injected between 0.4%SH group and the controlled group and NS group was also statistically significant under intention to treat and per protocol analysis (ITT: 0.03 ± 0.02 mL vs 0.06 ± 0.03 mL, P = 0.0003, PP: 0.03 ± 0.02 mL vs 0.06 ± 0.03 mL, P = 0.0004). Satisfaction above the grade good was significantly higher in the SH group under intention to treat and per protocol analysis (ITT: 90.91% vs 61.11%, P = 0.0041, PP = 93.11% vs 61.77%, P = 0.0022). Adverse events above grade 3 were not noticed in either group. All adverse events were treated and were judged as not associated with the submucosal injection solutions. CONCLUSION: 0.4%SH solution is a safe and effective agent that doesn't cause any significant adverse events and is useful for submucosal injection during ESD.

A case of synchronous esophagus and stomach cancer successfully treated by combined chemotherapy.

Although cases of simultaneous esophagus and stomach cancer have been reported sporadically, there are rare reports of successful treatment using chemotherapy. We report a case of synchronous esophageal and gastric cancer successfully treated using docetaxel and cis-diammineedichloro-platinum (CDDP) combination chemotherapy instead of surgery. A 82-years-old man with anorexia and progressive weight loss was diagnosed with synchronous esophageal and gastric cancer by endoscopy. Both cancers were diagnosed as resectable by the preoperative clinical staging. However, surgery was contraindicated because of severe lung dysfunction. Moreover, he actively refused radiotherapy and endoscopic management. Therefore, the patient was given combined chemotherapy with docetaxel (65 mg/m²) and CDDP (60 mg/m²). The esophageal and gastric lesion completely disappeared on endoscopy, and there were no residual tumor cells on endoscopic biopsy after three cycles of chemotherapy. Metastatic lymph nodes also completely disappeared on the CT scan. The patient received a total of ten cycles of chemotherapy, without severe adverse effects. The patient remained asymptomatic for 18 months after discontinuation of the chemotherapy, without evidence of local recurrence or distant metastasis. Surgery or endoscopic treatment of both esophageal and gastric cancers is desirable, but, if medically inoperable, chemotherapy can be alternative treatment option.

[Gastrointestinal metastasis from a primary adenocarcinoma of the lung presenting with acute abdominal pain].

Symptomatic gastro-intestinal metastasis in lung cancer is extremely rare and only a few case reports have been published. Here, we report a case with lung adenocarcinoma that presented with acute abdominal pain, nausea and vomiting due to duodenum, jejunum, and colon obstruction by the gastro-intestinal metastasis. The patient underwent colonoscopy and the pathologic report was adenocarcinoma. When there are similar histologic findings in both colon and pulmonary lesion, the question is whether both lesions are primary cancer or the colon lesions are metastases from lung cancer. Microscopic examination of a conventional pathologic section was not sufficient to make this determination. Immunohistochemistry was positive for thyroid transcription factor-1 (TTF-1) and cytokeratin 7 (CK7), and negative for cytokeratin 20 (CK20) and caudal-related homeobox transcription factor-2 (CDX-2) on colon mucosa specimen. Accordingly, we used immunohistochemical marker for differential diagnosis of primary adenocarcinoma of the lung with gastro-intestinal metastasis.

The removal of 1,4-dioxane from polyester manufacturing process wastewater using an up-flow Biological Aerated Filter (UBAF) packed with tire chips.

1,4-Dioxane is one of the by-products from the polyester manufacturing process, which has been carelessly discharged into water bodies and is a weak human carcinogen. In this study, a laboratory-scale, up-flow biological aerated filter (UBAF), packed with tire chips, was investigated for the treatment of 1,4-dioxane. The UBAF was fed with effluent, containing an average of 31 mg/L of 1,4-dioxane, discharged from an anaerobic treatment unit at H Co. in the Gumi Industrial Complex, South Korea. In the batch, a maximum of 99.5 % 1,4-dioxane was removed from an influent containing 25.6 mg/L. In the continuous mode, the optimal empty bed contact time (EBCT) and air to liquid flow rate (A:L) were 8.5 hours and 30:1, respectively. It was also found that the removal efficiency of 1,4-dioxane increased with increasing loading rate within the range 0.04 to 0.31 kg 1,4-dioxane/m(3)·day. However, as the COD:1,4-dioxane ratio was increased within the range 3 to 46 (mg/L COD)/(mg/L 1,4-dioxane), the removal efficiency unexpectedly decreased.

Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma.

AIM: To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma. METHODS: One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks. Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies. We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining. Coexistent nuclear localization was evaluated. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4. RESULTS: Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells, as well as showing weak cytoplasmic expression in non-neoplastic cells. By semiquantitative evaluation, positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%), Notch receptor 2 in 97 (88.2%), Notch receptor 3 in 97 (88.2%), Notch receptor 4 in 103 (93.6), and DLL4 in 84 (76.4%). In addition, coexistent nuclear localization was noted [Notch receptor 1; 18 cases (18.8%), Notch receptor 2; 40 (41.2%), Notch receptor 3; 32 (33.0%), Notch receptor 4; 99 (96.1%), DLL4; 48 (57.1%)]. Notch receptor 1 expression was correlated with advanced tumor, node, metastasis (TNM) stage (P = 0.043), Notch receptor 3 with advanced T stage (P = 0.017), tendency to express in cases with nodal metastasis (P = 0.065) and advanced TNM stage (P = 0.052). DLL4 expression tended to be related to less histological differentiation (P = 0.095). Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P = 0.027) and Notch receptor 4 with less histological differentiation (P = 0.036), while DLL4 tended to be related inversely with T stage (P = 0.053). Coexistent nuclear localization of DLL4 was related to poor survival (P = 0.002). CONCLUSION: Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression, and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.

Comparison of serum procalcitonin with Ranson, APACHE-II, Glasgow and Balthazar CT severity index scores in predicting severity of acute pancreatitis.

BACKGROUND/AIMS: The aim of this study is to assess serum procalcitonin (PCT) for early prediction of severe acute pancreatitis compared with multiple scoring systems and biomarkers. METHODS: Forty-four patients with acute pancreatitis confirmed by radiological evidences, laboratory assessments, and clinical manifestation were prospectively enrolled. All blood samples and image studies were obtained within 24 hours of admission. RESULTS: Acute pancreatitis was graded as severe in 19 patients and mild in 25 patients according to the Atlanta criteria. Levels of serum PCT were significantly higher in severe acute pancreatitis (p=0.001). The accuracy of serum PCT as a predicting marker was 77.3%, which was similar to the acute physiology and chronic health examination (APACHE)-II score, worse than the Ranson score (93.2%) and better than the Balthazar CT index (65.9%). The most effective cut-off level of serum PCT was estimated at 1.77 ng/mL (AUC=0.797, 95% CI=0.658-0.935). In comparision to other simple biomarkers, serum PCT had more accurate value (77.3%) than C-reactive protein (68.2%), urea (75.0%) and lactic dehydrogenase (72.7%). Logistic regression analysis revealed that serum PCT has statistical significance in acute severe pancreatitis. Assessment of serum PCT levels and length of hospital stay by simple linear regression analysis revealed effective p-value with low R square level, which could make only possibilty for affection of serum PCT to admission duration (r2=0.127, p=0.021). CONCLUSIONS: Serum PCT was a promising simple biomarker and had similar accuracy of APACHE-II scores as predicting severity of acute pancreatitis.

A study of metachronous cancer after endoscopic resection of early gastric cancer.

OBJECTIVE: Endoscopic resection is commonly used for early gastric cancer (EGC) in Korea and Japan. There are only a few reports of metachronous cancer after endoscopic resection. The aim of this study was to identify clinical factors associated with metachronous gastric cancer after endoscopic resection. METHODS: A total of 176 patients with EGC who had underwent endoscopic submucosal dissection (ESD) were periodically followed-up with endoscopic examinations from January 2004 to December 2007. The incidence and variable factors of metachronous gastric cancer were investigated in a retrospective study. RESULTS: The median interval between the diagnosis of primary cancer and the diagnosis of the first metachronous cancer was 30 months (range 18-42 months). Metachronous gastric cancer had developed in nine patients (5.1%) during follow-up period and seven patients (4.0%) had synchronous gastric cancer lesions within 1 year of the initial endoscopic treatment. Annual incidence rate of metachronous cancer was approximately 3.3%. Antrum atrophy and old age were significantly associated with the incidence of metachronous cancer. The status of Helicobacter pylori, size, location and gross finding of lesion had no significant relationship with metachronous occurrence. CONCLUSIONS: We should examine more carefully older patients who have atrophic gastritis because secondary cancer including metachronous cancer might occur in remnant stomach after initial successful endoscopic resection. And prospective study will be needed for the optimal endoscopic surveillance interval.

Splenic infarction associated with sorafenib use in a hepatocellular carcinoma patient.

Sorafenib, a multitargeted tyrosine kinase inhibitor, has been shown to improve survival in patients with advanced hepatocellular carcinoma (HCC). As the clinical use of sorafenib increases, many adverse effects have been reported, such as hand-foot skin reaction, diarrhea, anorexia, asthenia, alopecia, weight loss, hypertension and arterial thromboembolism. However, there are no prior reports of splenic infarction as an adverse effect of sorafenib. Here, a case of splenic infarction in a patient with HCC who was treated with sorafenib is reported. The patient had no other predisposing factors to explain the splenic infarction except for the administration of sorafenib. The splenic infarction improved after sorafenib was discontinued; however, the HCC progressed.

Efficacy of I-scan endoscopy in the diagnosis of gastroesophageal reflux disease with minimal change.

BACKGROUND/AIMS: The aim of the study was to evaluate the efficacy of i-scans for the diagnosis of gastroesophageal reflux disease, especially where only minimal change is involved. METHODS: The esophageal mucosa was inspected using an i-scan following conventional white light endoscopy. The examination with iscan was performed under tone enhancement (TE) esophagus (e) mode. Patients with subtle distal esophageal mucosal changes without definite mucosal breaks, such as blurring of Z-line (B), mucosal coarseness (C), hyperemic or purplish discoloration (D), erythema (E), ectopic gastric mucosal islet (I) and mixed type were classified as minimal change. RESULTS: A total of 156 patients were included. Using i-scan endoscopy, the number of minimal change was found to further increase from 94 (conventional endoscopy; 19B, 9C, 29D, 13E, 5I, 19 mixed type) to 109 (i-scan; 15B, 8C, 29D, 16E, 5I, 36 mixed type). And 14 patients who had single type by conventional endoscopy were converted to mixed type after i-scan. Therefore, 29 of 156 patients were upgraded after i-scan, they were account for 19% (p<0.0001; 95% confidence interval, 0.13 to 0.25). CONCLUSIONS: The use of i-scan endoscopy significantly improves the identification of minimal change and helps to identify more precisely the type of minimal change.

A case of pathologic splenic rupture as the initial manifestation of acute myeloid leukemia M2.

A pathologic splenic rupture refers to a rupture without trauma. A splenic rupture as the initial manifestation of acute myeloid leukemia is extremely rare. In this study, we described a rare case of acute myeloid leukemia presenting principally as an acute abdomen due to a pathologic splenic rupture in a 35-year old male patient. We can assert that a pathologic splenic rupture in hematologic diseases is a potentially life-threatening complication, which necessitates immediate operative intervention. Any such patient complaining about left upper abdominal tenderness should be closely observed, and further diagnostic investigations (ultrasonograph of the abdomen, abdominal CT scan) should be initiated in order to rule out a splenic rupture. The oncologist should be aware of this rare initial presentation of acute myeloid leukemia (AML) M2, as the condition generally necessitates a prompt splenectomy.

Efficacy of non-toxic deletion mutants of protective antigen from Bacillus anthracis.

Current human anthrax vaccines available in the United States and Europe consist of alum-precipitated supernatant material from cultures of a toxigenic, nonencapsulated strain of Bacillus anthracis. The major component of human anthrax vaccine that confers protection is protective antigen (PA). A second-generation human vaccine using the recombinant PA (rPA) is being developed. In this study, to prevent the toxicity and the degradation of the native rPA by proteases, we constructed two PA variants, delPA (163-168) and delPA (313-314), that lack trypsin (S(163)-R(164)-K(165)-K(166)-R(167)-S(168)) or chymotrypsin cleavage sequence (F(313)-F(314)), respectively. These proteins were expressed in Bacillus brevis 47-5Q. The delPAs were fractionated from the culture supernatant of B. brevis by ammonium sulfate at 70% saturation, followed by anion exchange chromatography on a Hitrap Q, Hiload 16/60 superdex 200 gel filtration column and phenyl sepharose hydrophobic interaction column. In accordance with previous reports, both delPA proteins combined with lethal factor protein did not show any cytotoxicity on J774A.1 cells. The delPA (163-168) and delPA (313-314) formulated either in Rehydragel HPA or MPL-TDM-CWS (Ribi-Trimix), elicited a comparable amount of anti-PA and neutralizing antibodies to those of native rPA in guinea pigs, and confers full protection of guinea pigs from 50xLD50 of fully virulent B. anthracis spore challenges. Ribi-Trimix was significantly more effective in inducing anti-PA and neutralizing antibodies than Rehydragel HPA. These results indicate the possibility of delPA (163-168) and delPA (313-314) proteins being developed into nontoxic, effective and stable recombinant vaccine candidates.