The Impact of Statins on the Survival of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib or Lenvatinib.

We aimed to evaluate the survival benefits of coadministering statins and multityrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC). Data from the Health Insurance Review and Assessment Service in Korea (2010-2020) were utilized. Statin use (≥28 cumulative defined daily doses) was analyzed, with 1534 statin users matched to 6136 non-users (1:4 ratio) using propensity scores. Primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS). Statin use significantly improved OS (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.72-0.82, p < 0.001) and PFS (HR 0.78, 95% CI 0.74-0.84, p < 0.001). Continuous or post-TKI statin users had better OS, while discontinuation after TKI use led to poorer OS. Both lipophilic and hydrophilic statins improved OS and PFS, particularly with ≥730 cumulative defined daily doses. In conclusion, combining statins and TKIs in patients with advanced HCC yielded significant survival benefits, influenced by statin dosage and duration. Continuous statin administration post-TKI treatment is crucial for improving outcomes in patients with HCC.

Positive faecal immunochemical test predicts the onset of inflammatory bowel disease: A nationwide, propensity score-matched study.

Background & aims: The faecal immunochemical test (FIT), a non-invasive test for screening colorectal cancer (CRC), is being increasingly understood to reflect heightened inflammation. We aimed to investigate the association between abnormal FIT results and onset of inflammatory bowel disease (IBD), a disease characterized with chronic gut mucosal inflammation. Methods: Participants in the Korean National Cancer Screening Program for CRC between 2009-2013 were analysed and divided into positive and negative FIT result groups. The incidence rates of IBD after screening were calculated after excluding cases of haemorrhoids, CRC, and IBD at baseline. Cox proportional hazard analyses were used to identify independent risk factors for IBD occurrence during follow-up, and 1:2 propensity score matching was performed as a sensitivity analysis. Results: In total, 229,594 and 815,361 participants were assigned to the positive and negative FIT result groups, respectively. The age- and sex-adjusted incidence rates of IBD in participants with positive and negative test results were 1.72 and 0.50 per 10,000 person-years, respectively. Adjusted Cox analysis revealed that FIT positivity was associated with a significantly higher risk of IBD (hazard ratio 2.93, 95% confidence interval: 2.46, 3.47, P <.001), which was consistent for both disease subtypes of ulcerative colitis and Crohn's disease. The results of Kaplan-Meier analysis in the matched population yielded identical findings. Conclusions: Abnormal FIT results could be a preceding sign of incident IBD in the general population. Those with positive FIT results and suspected IBD symptoms could benefit from regular screening for early disease detection.

Effect of Helicobacter pylori Eradication Treatment on Metachronous Gastric Neoplasm Prevention Following Endoscopic Submucosal Dissection for Gastric Adenoma.

The long-term effect of Helicobacter pylori eradication on metachronous gastric neoplasm prevention after endoscopic submucosal dissection (ESD) of gastric adenoma is unclear. This study included patients with confirmed H. pylori infection after ESD with curative resection for gastric adenoma. Patients were divided based on the success of H. pylori eradication treatment into two groups: eradication and non-eradication. Patients with any newly detected lesion within 1 year after ESD and recurrence at the ESD site were excluded from the analysis. Further, 1:1 propensity score matching was also performed to eliminate baseline differences between the two groups. H. pylori eradication treatment was administered to 673 patients after ESD (163 in the successful eradication group and 510 in the non-eradication group). During the median follow-up periods of 25 and 39 months in the eradication and non-eradication groups, metachronous gastric neoplasm was identified in 6 (3.7%) and 22 patients (4.3%), respectively. Adjusted Cox analysis revealed that H. pylori eradication was not associated with increased risk of metachronous gastric neoplasm after ESD. Kaplan-Meier analysis in the matched population yielded similar findings (p = 0.546). H. pylori eradication treatment was not associated with metachronous gastric neoplasm after ESD with curative resection for gastric adenoma.

Impact of guideline adherence on the prognosis of Barcelona clinic liver cancer stage B hepatocellular carcinoma.

BACKGROUND: Patients with Barcelona clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC) are considerably heterogeneous in terms of tumor burden, liver function, and performance status. To improve the poor survival outcomes of these patients, treatment approaches other than transarterial chemoembolization (TACE), which is recommended by HCC guidelines, have been adopted in real-world clinical practice. We hypothesize that this non-adherence to treatment guidelines, particularly with respect to the use of liver resection, improves survival in patients with stage B HCC. AIM: To assess guideline adherence in South Korean patients with stage B HCC and study its impact on survival. METHODS: A retrospective analysis was conducted using data from 2008 to 2016 obtained from the Korea Central Cancer Registry. Patients with stage B HCC were categorized into three treatment groups, guideline-adherent, upward, and downward, based on HCC guidelines recommended by the Asian Pacific Association for the Study of the Liver (APASL), the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Diseases (AASLD). The primary outcome was HCC-related deaths; tumor recurrence served as the secondary outcome. Survival among the groups was compared using the Kaplan-Meier method and the log-rank test. Predictors of survival outcomes were identified using multivariable Cox regression analysis. RESULTS: In South Korea, over the study period from 2008 to 2016, a notable trend was observed in adherence to HCC guidelines. Adherence to the EASL guidelines started relatively high, ranging from 77% to 80% between 2008 and 2012, but it gradually declined to 58.8% to 71.6% from 2013 to 2016. Adherence to the AASLD guidelines began at 71.7% to 75.9% from 2008 to 2010, and then it fluctuated between 49.2% and 73.8% from 2011 to 2016. In contrast, adherence to the APASL guidelines remained consistently high, staying within the range of 90.14% to 94.5% throughout the entire study period. Upward treatment, for example with liver resection, liver transplantation, or radiofrequency ablation, significantly improved the survival of patients with BCLC stage B HCC compared to that of patients treated in adherence to the guidelines (for patients analyzed according to the 2000 EASL guidelines, the 5-year survival rates were 63.4% vs 27.2%, P < 0.001), although results varied depending on the guidelines. Progression-free survival rates were also significantly improved upon the use of upward treatments in certain groups. Patients receiving upward treatments were typically < 70 years old, had platelet counts > 105/µL, and serum albumin levels ≥ 3.5 g/dL. CONCLUSION: Adherence to guidelines significantly influences survival in South Korean stage B HCC patients. Curative treatments outperform TACE, but liver resection should be selected with caution due to disease heterogeneity.

Long-term outcomes of endoscopic submucosal dissection and surgery for undifferentiated intramucosal gastric cancer regardless of size.

BACKGROUND: The clinical outcomes of endoscopic submucosal dissection (ESD) for undifferentiated (UD) intramucosal early gastric cancer (EGC) compared with those of surgery, regardless of lesion size, are not well known. Furthermore, there is a concern regarding the treatment plan before and after ESD in cases of UD intramucosal EGC within expanded indications. AIM: To evaluate clinical outcomes of ESD compared with those of surgery in UD intramucosal EGC patients regardless of tumor size. METHODS: We enrolled patients with UD intramucosal EGC after ESD with complete resection or surgery from January 2005 to August 2020 who met the within or beyond expanded indications with lesion size > 2 cm (the only non-curative factor). Overall, 123 and 562 patients underwent ESD and surgery, respectively. After propensity-score matching, clinical and long-term outcomes, i.e., recurrence-free survival (RFS) and overall survival (OS), were analyzed. The multivariable Cox proportional hazard model with treatment modality and ESD indication was used to evaluate the recurrence risk. RESULTS: After matching, 119 patients each were finally enrolled in the ESD and surgery groups. The median length of hospital stay was shorter in the ESD group than surgery group (4.0 vs 9.0 days, P < 0.001). Four cases of recurrence after ESD were local recurrences, all of which occurred within 1 year. Total recurrence was seven (5.9%) and two (1.7%) in the ESD and surgery groups, respectively. No difference was observed between the two groups with respect to OS (P = 0.948). However, the ESD group had inferior RFS compared with the surgery group (P = 0.031). ESD was associated with the risk of recurrence after initial treatment in all enrolled patients (hazard ratio, 5.2; 95% confidence interval: 1.0-25.8, P = 0.045). CONCLUSION: Although OS was similar between the two groups, surveillance endoscopy was important for the ESD than for the surgery group because RFS was inferior and local recurrence was an issue.

Risk factor-based optimal endoscopic surveillance intervals after endoscopic submucosal dissection for gastric adenoma.

To date, there exists no established endoscopic surveillance interval strategy after endoscopic submucosal dissection (ESD) for gastric adenoma. In this study, we suggest a risk factor-based statistical model for optimal surveillance intervals for gastric adenoma after ESD with curative resection. A cox proportional hazard model was applied to identify risk factors for recurrence after ESD. Patients (n = 698) were categorized into groups based on the identified risk factors. The cumulative density of recurrence over time was computed using a cubic splined baseline hazard function, and the customized surveillance interval was modeled for each risk group. The overall cumulative incidence of recurrence was 7.3% (n = 51). Risk factors associated with recurrence were male (hazard ratio [HR], 2.60, P = 0.030), protruded scar (HR, 3.18, P < 0.001), and age ≥ 59 years (HR, 1.05, P < 0.001). The surveillance interval for each group was developed by using the recurrence limit for the generated risk groups. According to the developed schedule, high-risk patients would have a maximum of seven surveillance visits for 5 years, whereas low-risk patients would have biennial surveillance for cancer screening. We proposed a simple and promising strategy for determining a better endoscopic surveillance interval by parameterizing diverse and group-specific recurrence risk factors into a well-known survival model.

Diagnostic Yield of Transabdominal Ultrasonography for Evaluation of Pancreatic Cystic Lesions Compared with Endoscopic Ultrasonography.

Detection rates of pancreatic cystic lesions (PCLs) have increased, resulting in greater requirements for regular monitoring using imaging modalities. We aimed to evaluate the capability of ultrasonography (US) for morphological characterization of PCLs as a reference standard using endoscopic ultrasonography (EUS). A retrospective analysis was conducted of 102 PCLs from 92 patients who underwent US immediately prior to EUS between January 2014 and May 2017. The intermodality reliability and agreement of the PCL morphologic findings of the two techniques were analyzed and compared using the intraclass correlation coefficient and κ values. The success rates of US for delineating PCLs in the head, body, and tail of the pancreas were 77.8%, 91.8%, and 70.6%, respectively. The intraclass correlation coefficient for US and the corresponding EUS lesion size showed very good reliability (0.978; p < 0.001). The κ value between modalities was 0.882 for pancreatic duct dilation, indicating good agreement. The κ values for solid components and cystic wall and septal thickening were 0.481 and 0.395, respectively, indicating moderate agreement. US may be useful for monitoring PCL growth and changes in pancreatic duct dilation, but it has limited use in the diagnosis and surveillance of mural nodules or cystic wall thickness changes.

A Diagnostic Method for Gastric Cancer Using Two-Photon Microscopy With Enzyme-Selective Fluorescent Probes: A Pilot Study.

BACKGROUND: Endoscopy is the most important tool for gastric cancer diagnosis. However, it relies on naked-eye evaluation by endoscopists, and the histopathologic confirmation is time-consuming. We aimed to visualize and measure the activity of various enzymes through two-photon microscopy (TPM) using fluorescent probes and assess its diagnostic potential in gastric cancer. METHODS: ß-Galactosidase (ß-gal), carboxylesterase (CES), and human NAD(P)H: quinone oxidoreductase (hNQO1) enzyme activities in the normal mucosa, ulcer, adenoma, and gastric cancer biopsy samples were measured using two-photon enzyme probes. The fluorescence emission ratio at long and short wavelengths (Ch2/Ch1) for each probe was comparatively analyzed. Approximately 8,000 - 9,000 sectional images in each group were obtained by measuring the Ch2/Ch1 ratio according to the tissue depth. Each probe was cross-validated by measuring enzymatic activity from a solution containing lysed tissue. RESULTS: Total of 76 subjects were enrolled in this pilot study (normal 21, ulcer 18, adenoma 17, and cancer 20 patients, respectively). There were significant differences in the mean ratio values of ß-gal (0.656 ± 0.142 vs. 1.127 ± 0.109, P < 0.001) and CES (0.876 ± 0.049 vs. 0.579 ± 0.089, P < 0.001) between the normal and cancer, respectively. The mean ratio value of cancer tissues was different compared to ulcer and adenoma (P < 0.001). The hNQO1 activity showed no significant difference between cancer and other conditions. Normal mucosa and cancer were visually and quantitatively distinguished through ß-gal and CES analyses using TPM images, and enzymatic activity according to depth, was determined using sectional TPM ratiometric images. The results obtained from lysis buffer-treated tissue were consistent with TPM results. CONCLUSIONS: TPM imaging using ratiometric fluorescent probes enabled the discrimination of gastric cancer from normal, ulcer, and adenoma. This novel method can help in a visual differentiation and provide quantitative depth profiling in gastric cancer diagnosis.

Bioelectrical impedance analysis for predicting postoperative complications and survival after liver resection for hepatocellular carcinoma.

BACKGROUND: Bioelectrical impedance analysis provides information on body composition and nutritional status. However, it's unclear whether the preoperative edema index or phase angle predicts postoperative complication or mortality in patients with hepatocellular carcinoma (HCC). Thus, we investigated whether preoperative bioelectrical impedance analysis could predict postoperative complications and survival in patients with HCC. METHODS: Seventy-nine patients who underwent hepatectomy for hepatocellular carcinoma were prospectively enrolled and bioelectrical impedance analysis was performed before surgery. Postoperative ascites or acute kidney injury and patients' survival were monitored after surgery. RESULTS: Among 79 patients, 35 (44.3%) developed ascites or acute kidney injury after hepatectomy. In multivariate analysis, a high preoperative edema index (extracellular water/total body water) (>0.384) (odds ratio 3.96; 95% confidence interval: 1.03-15.17; P=0.045) and higher fluid infusion during surgery (odds ratio 1.36; 95% confidence interval: 1.04-1.79; P=0.026) were identified as significant risk factors for ascites or acute kidney injury after hepatectomy. Subgroup analyses showed that the edema index was a significant predictor of ascites or acute kidney injury in patients with cirrhosis. Tumor size was the only significant predictive factor for short-term survival after hepatectomy. CONCLUSIONS: The preoperative edema index using bioelectrical impedance analysis can be used as a predictor of post-hepatectomy complication, especially in patients with liver cirrhosis.

Association of Intensive Endoscopic Screening Burden With Gastric Cancer Detection.

Importance: The rapidly increasing number of gastric cancer examinations performed over a short period might influence screening performance. Accessing the association between calendar month and gastric cancer detection rates might improve policy and guide institutional support. Objective: To evaluate the association between the increased number of examinations over a certain period and gastric cancer detection rates among a large population included in the Korean National Cancer Screening Program (KNCSP). Design, Setting, and Participants: This retrospective, population-based cohort study used data from the KNCSP comprising 26 765 665 men and women aged 40 years or older who participated in the screening program between January 1, 2013, and December 31, 2016. Data were analyzed from November 1, 2019, to March 31, 2020. Exposures: Gastric cancer screening with endoscopy. Main Outcomes and Measures: The primary outcome was monthly gastric cancer detection rates in the KNCSP. A negative binomial regression model was used to evaluate the association between the screening month and detection rates. Results: In total, 21 535 222 individuals underwent endoscopy (mean [SD] age, 55.61 [10.61] years; 11 761 709 women [54.62%]). The quarterly number of participants was the highest in the last quarter of the study period (2013-2014: 4 094 951 [41.39%], 2015-2016: 4 911 629 [42.19%]); this proportion was 2.48 to 2.84 times greater than that of the first quarter. Cancer detection rates were the lowest in December (2013-2014: 0.22; 95% CI, 0.22-0.23; 2015-2016: 0.21; 95% CI, 0.21-0.22); this was approximately a 40.0% to 45.0% reduction compared with the rates in January. The age group was the significant factor for monthly detection rates. After adjustment for the age group and taking account of the number of screenings, the estimated coefficient range for the screening month was negative and the detection rate in December was significantly different than in January for both the consequent cycles (2013-2014: -0.05 to -0.18; P < .001; and 2015-2016: -0.06 to -0.19; P < .001). In the multivariable logistic model, the association of calendar month with detected cancer remained after adjusting for other confounding factors (December, 2013-2014: odds ratio, 0.82; 95% CI, 0.76-0.87; P < .001; 2015-2016: odds ratio, 0.83; 95% CI, 0.79-0.89; P < .001). Conclusions and Relevance: The findings of this cohort study suggest that the workload of endoscopists increased with the increasing number of examinations toward the end of the year, as demonstrated by the decreased cancer detection rates. These findings may help to improve gastric cancer detection rates of screening programs by controlling the monthly screening number and policy modifications.

Association Between Waiting Time from Diagnosis to Endoscopic Submucosal Dissection and Non-curative Resection in Gastric Neoplasm.

BACKGROUND/AIM: Currently, there are no standard guidelines for the waiting time from the diagnosis of gastric neoplasms to endoscopic submucosal dissection (ESD). PATIENTS AND METHODS: A total of 1,605 patients who had undergone ESD for early gastric cancer (EGC) or high-grade dysplasia (HGD) were enrolled. Waiting time for ESD was defined as the time from the first diagnosis to ESD. Multivariable logistic regression analysis was conducted. RESULTS: The curative resection rate was 86.8% and the mean waiting time was 36.8 days. In the multivariable model, longer waiting time did not significantly affect non-curative resection, whereas age >70 years, submucosal fibrosis, and initial cancer diagnosis were significantly associated with non-curative resection. Waiting time was still not identified as a risk factor for non-curative resection in EGC and HGD groups. CONCLUSION: A longer waiting time from diagnosis to ESD was not associated with non-curative resection.

Association of Regular Endoscopic Screening with Interval Gastric Cancer Incidence in the National Cancer Screening Program.

Although regular endoscopic screening may help in early detection of gastric cancer, interval cancer remains a problem in the screening program. This study evaluated the association between regular endoscopic screening and interval cancer detection in the Korean National Cancer Screening Program (KNCSP). We defined three groups (regularly, irregularly, and not screened) according to the screening interval, and the trends in the interval cancer rate (ICR) between the groups were tested using the Cochran-Armitage test. The influence of regular endoscopic screening on the risk of interval cancer was evaluated using multivariable logistic regression. Among the 11,642,410 participants who underwent endoscopy, the overall ICR was 0.36 per 1000 negative screenings. The ICR of the not screened group (0.41) was the highest among the three groups and the risk of interval cancer in this group was 1.68 times higher (p < 0.001) than that in the regularly screened group. Women in their 40s who had regular screening with no history of intestinal metaplasia and gastric polyps would have the lowest probability of having interval cancer (0.005%). Regular participation in endoscopic screening programs for reducing the risk of interval cancer may help to improve the quality of screening programs.

Diagnostic accuracy of "sweeping" method compared to conventional sampling in rapid urease test for Helicobacter pylori detection in atrophic mucosa.

Although the rapid urease test (RUT) is a simple method for detecting Helicobacter pylori (H. pylori) infection, it requires sufficient biopsy samples and its sensitivity varies depending on the site and condition of H. pylori infection. We compared the diagnostic performance of a "sweeping method" for H. pylori detection with the conventional biopsy sampling method in atrophic gastric conditions which can reduce RUT accuracy. This prospective study included 279 patients who underwent upper endoscopy to determine the presence of H. pylori infection. Gastric mucosa of both the antrum and the corpus were swabbed, and we named this method the "sweeping method". Biopsy sampling for the conventional method, histologic evaluation, and polymerase chain reaction were performed at the same time. The sensitivity, specificity, and accuracy of the sweeping method were 0.941, 0.826, and 0.903, respectively, compared to 0.685, 0.859, and 0.742, respectively, for the conventional biopsy method. The area under the receiver operating curve for the sweeping method was 0.884 versus 0.772 for the conventional method (P < 0.001). The sweeping method had a faster detection time than the conventional method. Compared to conventional biopsy sampling, the sweeping method with the RUT provided higher sensitivity and accuracy for the detection of H. pylori, with a faster detection time.

Comparison of Effectiveness between Abdominal Vibration Stimulation and Walking Exercise for Bowel Cleansing before Therapeutic Colonoscopy.

Background/Aims: Adequate bowel preparation is important for successful colonoscopy. We aimed to evaluate the clinical feasibility and effectiveness of abdominal vibration stimulation in bowel preparation before therapeutic colonoscopy. Methods: A single center, prospective, randomized, investigator-blinded study was performed between January 2016 and December 2016. Patients for therapeutic colonoscopy were prospectively enrolled and assigned to either the vibrator group or walking group. Patients who refused to participate in this study as part of the experimental group consented to register in the control group instead. During the preparation period, patients assigned to the walking group walked ≥3,000 steps, whereas those assigned to the vibrator group received abdominal vibrator stimulation and restricted walking. All patients received the same colon cleansing regimen: 4-L split-dose polyethylene glycol (PEG) solution. Results: Three hundred patients who received PEG solution for therapeutic colonoscopy were finally enrolled in this study (n=100 per group). Bowel cleansing with abdominal vibration stimulation showed almost similar results to that with walking exercise (Boston Bowel Preparation Scale score for the entire colon: vibrator vs walking vs control, 7.38±1.55 vs 7.39±1.55 vs 6.17±1.15, p<0.001). There were no significant differences between the vibrator group and walking group regarding instances of diarrhea after taking PEG, time to first diarrhea after taking PEG, total procedure time, and patient satisfaction. Conclusions: This study indicates that, compared with conventional walking exercise, abdominal vibration stimulation achieved similar rates of bowel cleansing adequacy and colonoscopy success without compromising safety or patient satisfaction.

EpCAM as a Predictive Marker of Tumor Recurrence and Survival in Patients Who Underwent Surgical Resection for Hepatocellular Carcinoma.

BACKGROUND/AIM: Epithelial cell adhesion molecule (EpCAM) is expressed in hepatic progenitor cells and hepatocellular carcinoma (HCC), and is considered a marker of liver cancer stem cells. MATERIALS AND METHODS: A total of 262 patients were enrolled who had undergone surgical resection for HCC, with immunohistochemical staining results for EpCAM. The immunohistochemical expression of EpCAM and other stemness-related markers was evaluated as prognosticators of tumor recurrence and survival in patients who underwent surgical resection for HCC. RESULTS: A multivariate Cox regression analysis showed that tumor size [hazard ratio (HR)=2.26, p=0.005], intrahepatic metastasis (HR=2.31, p=0.011), and EpCAM positivity (HR=1.74, p=0.038) were associated with tumor recurrence. In a Kaplan-Meier survival analysis, patients with EpCAM-positive tumors had a significantly higher tumor recurrence rate and a reduced overall survival compared to those with EpCAM-negative tumors. CONCLUSION: Immunohistochemical expression of EpCAM was identified as a poor prognosticator of recurrence and survival after surgical resection in patients with HCC.

Clinical significance of incidental prostatic fluorine-18-fluorodeoxyglucose uptake in the diagnosis of infectious prostatitis in adult males.

BACKGROUND: We performed a work-up study of cancer patients with incidentally found uncharacterized prostatic fluorine-18-fluorodeoxyglucose (F-FDG) uptake in F-FDG PET/CT results. Then, we evaluated the clinical significance of the incidental prostate F-FDG uptake (IPU) in nonmalignant prostate tissues. PATIENTS AND METHODS: Overall, 51 men agreed to a physical prostate examination and an expressed prostatic secretion (EPS) test within 2 weeks after torso F-FDG PET/CT scans. We then reviewed the F-FDG PET/CT scans of the enrolled patients and evaluated the relationship between the F-FDG PET/CT, prostate-specific antigen, and prostatic laboratory findings. RESULTS: The pathological diagnosis of five men indicated the presence of prostate cancer, and of the remaining 46 men, 27 cases showed IPU in the F-FDG PET/CT whereas 19 did not. The characteristics of the enrolled patients were as follows: mean age of 61.15±13.79 years (range: 30-83 years), maximum standardized uptake value of 2.64±1.33 (range: 1.2-7.1), and prostate-specific antigen of 3.10±3.50 ng/ml (range: 0.16-13.55 ng/ml). Ten of the 27 (37%) patients with IPU in the PET/CT scan showed bacterial infections in their prostate. A multivariate analysis indicated that the bacterial presence in the EPS increased the risk of IPU (adjusted odds ratio: 9.167; P=0.019). CONCLUSION: Bacterial presence in the prostate tends to increase the likelihood of IPU in F-FDG PET/CT scans. Therefore, men with incidental prostate F-FDG uptake should be considered for a possible prostate infection in addition to a concomitant malignancy.

Non-neoplastic pathology results after endoscopic submucosal dissection for gastric epithelial dysplasia or early gastric cancer.

BACKGROUND AND STUDY AIMS: Endoscopists sometimes face paradoxical cases in which the endoscopic submucosal dissection (ESD) specimen reveals a non-neoplastic pathology result. The aims of the study were to determine the reasons for such results, and to compare the endoscopic characteristics of non-neoplastic and conventional neoplastic pathology groups after ESD. PATIENTS AND METHODS: A total of 1186 gastric ESDs performed between February 2005 and December 2011 were retrospectively reviewed. The ESD specimens included 52 (4.4 %) that were confirmed as negative or indefinite for neoplasia. Patient characteristics and endoscopic and pathological data were reviewed and compared. RESULTS: Non-neoplastic pathology after ESD was due to complete removal of the lesion at biopsy in 45 cases (86.5 %), pathology overestimation in 5 (9.6 %), and incorrect localization of the original tumor with subsequent ESD performed at the wrong site in 2 (3.8 %). The mean length and surface area of the non-neoplastic lesions were 9.2 ±â€Š2.6 mm and 49.6 ±â€Š23.6 mm (2), respectively. Mean sampling ratios were 3.0 ±â€Š1.5 mm/fragment and 16.3 ±â€Š10.0 mm(2)/fragment. Compared with 1134 cases confirmed as neoplastic on the final ESD specimen, non-neoplastic cases showed a significantly smaller tumor size and surface area, and lower sampling ratios in a logistic regression analysis adjusted for potential confounders (P < 0.001 for all). CONCLUSIONS: Complete lesion removal by biopsy, pathology overestimation, and incorrect localization of the original tumor with subsequent ESD at the wrong site were the main reasons for non-neoplastic results after ESD. Small tumor size and surface area, and low sampling ratios were associated with non-neoplastic pathology results after ESD.

Inter-alpha-trypsin inhibitor heavy chain H4 as a diagnostic and prognostic indicator in patients with hepatitis B virus-associated hepatocellular carcinoma.

OBJECTIVES: Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) is associated with various diseases. We evaluated the diagnostic and prognostic significance of serum ITIH4 levels in healthy controls and patients with chronic hepatitis B (CHB), hepatitis B virus (HBV)-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC). DESIGN AND METHODS: The study enrolled 300 individuals (50 healthy controls, 50 with CHB, 100 with HBV-associated cirrhosis, and 100 with HBV-associated HCC). Serum ITIH4 levels were determined by western blot analysis and expressed in densitometry units (DU). RESULTS: ITIH4 levels were higher in CHB (mean: 252.96 DU) and liver cirrhosis (mean: 206.43 DU) patients than in healthy controls (mean: 75.92 DU) and HCC patients (mean: 92.86 DU) (P<0.001). The area under the receiver operating characteristic curve was 0.71 for the diagnosis of HCC in patients with HBV-related liver disease. Multivariate Cox regression analysis showed that large tumor size (≥5 cm) was independently associated with overall survival (hazard ratio 5.894, 95% confidence interval 1.373-25.300, P=0.017). A Kaplan-Meier survival analysis showed significantly worse survival among HCC patients with both low ITIH4 (<80 DU) and a large tumor size compared to that among other HCC patients (P<0.001), and among patients with high AFP (>200 ng/mL) and low ITIH4 compared to that among other HCC patients (P=0.041). CONCLUSIONS: Serum ITIH4 levels are reduced in HCC patients compared to that in CHB and cirrhosis patients, and low serum ITIH4 levels are associated with shorter survival in HBV-associated HCC patients.

Recombinant expression and refolding of the c-type lysozyme from Spodoptera litura in E. coli

The chicken-type lysozyme of the insect Spodoptera litura (SLLyz) is a polypeptide of 121 amino acids containing four disulfide bridges and 17 rare codons and participates in innate defense as an anti-bacterial enzyme. The recombinant S. litura lysozyme (rSLLyz) expressed as a C-terminal fusion protein with glutathione S-transferase (GST) in Rosetta(DE3) Singles. The protein was produced as an inclusion body which was solubilized in 8 M urea, renatured by on-column refolding, and purified by reversed-phase chromatography to 95 percent purity. The purified rSLLyz demonstrated antibacterial activity against B. megaterium confirmed by inhibition zone assay. The overexpression and refolding strategy described in this study will provide a reliable technique for maximizing production and purification of proteins expressed as inclusion bodies in E. coli.