Current diagnosis and treatment of benign biliary stricturesafter living donor liver transplantation

Despite advances in surgical techniques, benign biliary strictures after living donor liver transplantation(LDLT) remain a significant biliary complication and play an important role in graft and patient survival. Benign biliary strictures after transplantation are classified into anastomotic or non-anastomotic strictures. These two types differ in presentation, outcome, and response to therapy. The leading causes of biliary strictures include impaired blood supply, technical errors during surgery, and biliary anomalies. Because patients usually have non-specific symptoms, a high index of suspicion should be maintained. Magnetic resonance cholangiography has gained widespread acceptance as a reliable noninvasive tool for detecting biliary complications. Endoscopy has played an increasingly prominent role in the diagnosis and treatment of biliary strictures after LDLT. Endoscopic management in LDLT recipients may be more challenging than in deceased donor liver transplantation patients because of the complex nature of the duct-to-duct reconstruction. Repeated aggressive endoscopic treatment with dilation and the placement of multiple plastic stents is considered the first-line treatment for biliary strictures. Percutaneous and surgical treatments are now reserved for patients for whom endoscopic management fails and for those with multiple, inaccessible intrahepatic strictures or Roux-en-Y anastomoses. Recent advances in enteroscopy enable treatment, even in these latter cases. Direct cholangioscopy, another advanced form of endoscopy, allows direct visualization of the inner wall of the biliary tree and is expected to facilitate stenting or stone extraction. Rendezvous techniques can be a good option when the endoscopic approach to the biliary stricture is unfeasible. These developments have resulted in almost all patients being managed by the endoscopic approach.

Anemia after gastrectomy for early gastric cancer:Long-term follow-up observational study

AIM:To identify the incidence and etiology of anemia after gastrectomy in patients with long-term follow-up after gastrectomy for early gastric cancer.METHODS:The medical records of those patients with early gastric adenocarcinoma who underwent curative gastrectomy between January 2006 and October 2007 were reviewed.Patients with anemia in the preoperative workup,cancer recurrence,undergoing systemic chemotherapy,with other medical conditions that can cause anemia,or treated during follow up with red cell transfusions or supplements for anemia were excluded.Anemia was defined by World Health Organization criteria(Hb < 12 g/dL in women and < 13 g/dL in men).Iron deficiency was defined as serum ferritin < 20 g/dL.Vitamin B12 deficiency was defined as serum vitamin B 12 < 200 pg/mL.Iron deficiency anemia was defined as anemia with concomitant iron deficiency.Anemia from vitamin B 12 deficiency was defined as megaloblastic anemia(mean cell volume > 100 fL) with vitamin B 12 deficiency.The profile of anemia over 48 mo of follow-up was analyzed.RESULTS:One hundred sixty-one patients with gastrectomy for early gastric cancer were analyzed.The incidence of anemia was 24.5% at 3 mo after surgery and increased up to 37.1% at 48 mo after surgery.The incidence of iron deficiency anemia increased during the follow up and became the major cause of anemia at 48 mo after surgery.Anemia of chronic disease and megaloblastic anemia were uncommon.The incidence of anemia in female patients was significantly higher than in male patients at 12(40.0% vs 22.0%,P = 0.033),24(45.0% vs 25.0%,P = 0.023),36(55.0% vs 28.0%,P = 0.004),and 48 mo(52.0% vs 31.0%,P = 0.022) after surgery.Patients with total gastrectomy showed significantly higher incidence of anemia than patients with subtotal gastrectomy at 48 mo after surgery(60.7% vs 31.3%,P = 0.008).The incidence of iron deficiency was significantly higher in female patients than in male patients at 6(35.4% vs 13.3%,P = 0.002),12(45.8% vs 16.8%,P < 0.001),18(52.1% vs 22.3%,P < 0.001),24(60.4% vs 20.9%,P < 0.001),36(62.5% vs 29.2%,P < 0.001),and 48 mo(66.7% vs 34.7%,P = 0.001) after surgery.CONCLUSION:Anemia was frequent after gastrectomy for early gastric cancer,with iron deficiency being the major cause.Evaluation for anemia including iron status should be performed after gastrectomy and appropriate iron replacement should be considered.

Helicobacter pylori infection is not associated with nonalcoholic fatty liver disease

AIM: To determine whether Helicobacter pylori(H. pylori) infection confers a higher risk of Nonalcoholic fatty liver disease(NAFLD).METHODS: Healthy people who underwent health screening were analyzed retrospectively. Inclusion criteria were age ≥ 20 years, history of H. pylori infection, and recorded insulin level. Participants were classified as H. pylori positive or negative according to 13 C urea breath tests. NAFLD was defined using the hepatic steatosis index(HSI) and NAFLD liver fat score(NAFLD-LFS). Those with an HSI > 36 or NAFLD-LFS >-0.640 were considered to have NAFLD. Multivariable logistic regression was performed to identify risk factors for NAFLD.RESULTS: Three thousand six hundred and sixtythree people were analyzed and 1636(44.7%) were H. pylori positive. H. pylori infection was associated with older age, male gender, hypertension, higher body mass index, and a dyslipidemic profile. HSI differed significantly between H. pylori positive and negative subjects(median 33.2, interquartile range(IQR) 30.0-36.2 for H. pylori-positive vs median 32.6, IQR 29.8-36.0 for negative participants, P = 0.005), but NAFLD-LSF did not [median-1.7, IQR-2.4--0.7 vs median-1.8, IQR-2.4-(-0.7), respectively, P = 0.122]. The percentage of people with NAFLD did not differbetween infected and uninfected groups: HIS, 26.9% vs 27.1%, P = 0.173; NAFLD-LFS, 23.5% vs 23.1%, P = 0.778. H. pylori infection was not a risk factor, but C-reactive protein concentration and smoking were significant risk factors for NAFLD.CONCLUSION: H. pylori infection is not a risk factor for NAFLD as indicated by HSI or NAFLD-LFS. Prospective, large-scale studies involving liver biopsies should be considered.

Chronic gastrointestinal symptoms and quality of life in the Korean population

AIM: To evaluate the prevalence of chronic gastroin-testinal symptoms and their impact on health-related quality of life (HRQOL) in the Korean population. METHODS: A cross-sectional survey, using a reliable and valid Rome Ⅱ based questionnaire, was per-formed on randomly selected residents, between 18 and 69 years in age. All respondents were interviewed at their homes or offices by a team of interviewers. The impact of chronic gastrointestinal symptoms on HRQOL was assessed using the Korean version of the 36-item Short-Form general health survey (SF-36). RESULTS: Of the 1807 eligible subjects, 1417 (78.4%: male 762; female 655) were surveyed. Out of the respondents, 18.6% exhibited at least one chronic gastrointestinal symptom. The prevalence of gastro- esophageal reflux disease (GERD), defined as heart- burn and/or acid regurgitation experienced at least weekly, was 3.5% (95% CI, 2.6-4.5). The prevalence of uninvestigated dyspepsia, irritable bowel syndrome (IBS) and chronic constipation based on Rome Ⅱ cri- teria were 11.7% (95% CI, 10.1-13.5), 2.2% (95%CI, 1.5-3.1), and 2.6% (95% CI, 1.8-3.5) respectively. Compared with subjects without chronic gastrointesti- nal symptoms (n = 1153), those with GERD (n = 50), uninvestigated dyspepsia (n = 166) and IBS (n = 31) had signifi cantly worse scores on most domains of the SF-36 scales. CONCLUSION: The prevalence of GERD, uninvesti-gated dyspepsia and IBS were 3.5%, 11.7% and 2.2% respectively, in the Korean population. The health- related quality of life was signifi cantly impaired in sub-jects with GERD, uninvestigated dyspepsia and IBS in this community.

Evaluation of esophageal function in patients with esophageal motor abnormalities using multichannel intraluminal impedance esophageal manometry

AIM: To evaluate the functional aspect of esophageal motility in healthy subjects and in patients who were referred for esophageal function testing using multichannel intraluminal impedance-esophageal manometry (MII-EM), and to assess the clinical utility of MII-EM. METHODS: From September 2003 to January 2004, we performed the MII-EM on healthy volunteers and all the patients who were referred for esophageal function testing. Each patient received 10 liquid and 10 viscous swallows. We analyzed the results, the impedance and the manometric findings. Some of the subjects had additional ambulatory 24-h pH study performed to diagnose gastroesophageal reflux disease (GERD). RESULTS: Among 89 studied subjects, the MII-EM findings showed normal esophageal motility in 50 (56.17%), ineffective esophageal motility (IEM) in 17 (19.10%), nutcracker esophagus in 7 (7.86%), achalasia in 4 (4.49%), and scleroderma esophagus in 11 (12.35%) cases. The completeness and the speed of bolus transit were in the order of nutcracker esophagus, normal manometry and IEM. Some of the swallows showing normal manometry and IEM had incomplete transit. In the achalasia and scleroderma esophagus, almost all the swallows had incomplete transit. The body amplitudes were higher for the swallows with complete transit than for the swallows with incomplete transit. There was not a significant difference in the manometric and impedance findings between the subjects with and without GERD. CONCLUSION: MII-EM is a useful tool in assessing theesophageal function in the patients having esophageal motility abnormality. The primary factors influencing the bolus transit are the amplitude of the esophageal body and normal peristalsis.

Clinical outcomes of self-expandable metal stents in palliation of malignant anastomotic strictures caused by recurrent gastric cancer

AIM:To examine the technical feasibility and clinical outcomes of the endoscopic insertion of a self-expandable metal stent(SEMS) for the palliation of a malignant anastomotic stricture caused by recurrent gastric cancer.METHODS:The medical records of patients, who had obstructive symptoms caused by a malignant anastomotic stricture after gastric surgery and underwent endoscopic insertion of a SEMS from January 2001 to December 2007 at Kangnam St Mary's Hospital, were reviewed retrospectively.RESULTS:Twenty patients(15 male, mean age 63 years) were included.The operations were a total gastrectomy with esophagojejunostomy(n = 12), subtotal gastrectomy with Billroth-—migration occurred with a covered stent in 3 patients who underwent a subtotal gastrectomy with Billroth-reconstruction.Two cases of partial stent migration were easily treated with a second stent or stent repositioning.The median stent patency was 56 d(range, 5-439 d).The median survival was 83 d(range, 12-439 d).CONCLUSION:Endoscopic insertion of a SEMS provides safe and effective palliation of a recurrent anastomotic stricture caused by gastric cancer.A meticulous evaluation of the presence of other strictures before inserting the stent is essential for symptom improvement.

Comparative study of rendezvous techniques in post-liver transplant biliary stricture

AIM:To investigate the usefulness of a new rendezvous technique for placing stents using the Kumpe(KMP) catheter in angulated or twisted biliary strictures.METHODS:The rendezvous technique was performed in patients with a biliary stricture after living donor liver transplantation(LDLT) who required the exchange of percutaneous transhepatic biliary drainage catheters for inside stents.The rendezvous technique was performed using a guidewire in 19 patients(guidewire group) and using a KMP catheter in another 19(KMP catheter group).We compared the two groups retrospectively.RESULTS:The baseline characteristics did not differ between the groups.The success rate for placing inside stents was 100% in both groups.A KMP catheter was easier to manipulate than a guidewire.The mean procedure time in the KMP catheter group(1012 s,range:301-2006 s) was shorter than that in the guidewire group(2037 s,range:251-6758 s,P = 0.022).The cumulative probabilities corresponding to the procedure time of the two groups were significantly different(P = 0.008).The factors related to procedure time were the rendezvous technique method,the number of inside stents,the operator,and balloon dilation of the stricture(P < 0.05).In a multivariate analysis,the rendezvous technique method was the only significant factor related to procedure time(P = 0.010).The procedural complications observed included one case of mild acute pancreatitis and one case of acute cholangitis in the guidewire group,and two cases of mild acute pancreatitis in the KMP catheter group.CONCLUSION:The rendezvous technique involving use of the KMP catheter was a fast and safe method for placing inside stents in patients with LDLT biliary stricture that represents a viable alternative to the guidewire rendezvous technique.

Effect of DA-9701 on gastric emptying in a mouse model: Assessment by ^(13)C-octanoic acid breath test

AIM:To evaluate the effects of DA-9701 on the gastric emptying of a solid meal using the 13C-octanoic acid breath test in a mouse model. METHODS:Male C57BL/6 mice aged > 8 wk and with body weights of 20-25 g were used in this study. The solid test meal consisted of 200 mg of egg yolk labeled with 1.5 L/g 13C-octanoic acid. The mice were placed in a 130 mL chamber flushed with air at a flow speed of 200 mL/min. Breath samples were collected for 6 h. The half-emptying time and lag phase were calculated using a modified power exponential model. To assess the reproducibility of the 13C-octanoic acid breath test, the breath test was performed two times at intervals of one week in ten mice without drug treatment. To assess the gastrokinetic effects of DA-9701, the breath test was performed three times in another twelve mice, with a randomized crossover sequence of three drug treatments:DA-9701 3 mg/kg, erythromycin 6 mg/kg, or saline. Each breath test was performed at an interval of one week. RESULTS:Repeatedly measured half gastric emptying time of ten mice without drug treatment showed 0.856 of the intraclass correlation coefficient for the half gastric emptying time (P = 0.004). The mean cumulative excretion curve for the 13C-octanoic acid breath test showed accelerated gastric emptying after DA-9701 treatment compared with the saline control (P = 0.028). The median half gastric emptying time after the DA-9701 treatment was significantly shorter than after the saline treatment [122.4 min (109.0-137.9 min) vs 134.5 min (128.4-167.0 min), respectively; P = 0.028] and similar to that after the erythromycin treatment [123.3 min (112.9-138.2 min)]. The lag phase, which was defined as the period taken to empty 15% of a meal, was significantly shorter after the DA-9701 treatment than after the saline treatment [48.1 min (44.6-57.1 min) vs 52.6 min (49.45-57.4 min), respectively; P = 0.049]. CONCLUSION:The novel prokinetic agent DA-9701 accelerated gastric emptying, assessed with repeated measurements in the same mouse using the 13Coctanoic acid breath test. Our findings suggest that DA-9701 has therapeutic potential for the treatment of functional dyspepsia.

Severe thrombocytopenia before liver transplantation is associated with delayed recovery of thrombocytopenia regardless of donor type

AIM: To compare the recovery of thrombocytopenia and splenomegaly during long-term follow-up after liver transplantation in patients receiving a living donor transplant or a cadaveric donor transplant. METHODS: This was a retrospective cohort study of 216 consecutive liver transplant patients who survived for > 6 mo after transplantation; 169 received a liver transplant from a living donor and 47 from a cadaveric donor. The platelet counts or spleen volumes were examined before transplant, 1, 6, and 12 mo after transplant, and then annually until 5 years after transplant. RESULTS: The mean follow-up period was 49 mo (range, 21-66). Platelet counts increased continu-ously for 5 years after orthotopic liver transplant. The restoration of platelet counts after transplant was sig-nificantly slower in patients with severe pretransplant thrombocytopenia (< 50 000/μL) until 4 years after transplant (P = 0.005). Donor type did not significantly affect the recovery of platelet count and spleen vol-ume in either patient group. In multivariate analysis, pretransplant severe thrombocytopenia (< 50 000/μL) was an independent factor associated with sustained thrombocytopenia (P < 0.001, odds ratio 6.314; con-fidence interval, 2.828-14.095). Thrombocytopenia re-appeared after transplant in seven patients with portal flow disturbance near the anastomosis site. CONCLUSION: Our study suggests that severe throm-bocytopenia before transplant is closely associated with delayed recovery of platelet count after transplant and donor type did not affect the recovery of throm-bocytopenia. The reappearance of thrombocytopenia after transplant should be considered a possible indica-tor of flow disturbance in the portal vein.

Long-term pretreatment with proton pump inhibitor and Helicobacter pylori eradication rates

AIM:To investigate whether proton pump inhibitor(PPI)pretreatment influences Helicobacter pylori eradication rate.METHODS:We retrospectively reviewed H.pylori-infected patients who were treated with a standard triple regimen(PPI,amoxicillin 1 g,and clarithromycin 500mg,all twice daily for 7 d).The diagnosis of H.pylori infection and its eradication was assessed with the rapid urease test,histological examination by silver staining,or the13C-urea breath test.We divided the patients into two groups:one received the standard eradication regimen without PPI pretreatment(Group A),and the other received PPI pretreatment(Group B).The patients in Group B were reclassified into three groups based on the duration of PPI pretreatment:Group B-Ⅰ(3-14 d),Group B-Ⅱ(15-55 d),and Group B-Ⅲ(≥56 d).RESULTS:A total of 1090 patients were analyzed and the overall eradication rate was 80.9%.The cure rate in Group B(81.2%,420/517)was not significantly different from that in Group A(79.2%,454/573).The eradication rates in Group B-Ⅰ,B-Ⅱand B-Ⅲwere80.1%(117/146),81.8%(224/274)and 81.4%(79/97),respectively.CONCLUSION:PPI pretreatment did not affect H.pylori eradication rate,regardless of the medication period.

Hematologic diseases: High risk of Clostridium difficile associated diarrhea

AIM:To investigate the incidence and clinical outcome of Clostridium difficile(C.difficile)associated diarrhea(CDAD)in patients with hematologic disease.METHODS:We retrospectively reviewed the medical records of patients who underwent C.difficile testing in a tertiary hospital in 2011.The incidence and risk factors for CDAD and its clinical course including recurrence and mortality were assessed in patients with hematologic disease and compared with those in patients with nonhematologic disease.RESULTS:About 320 patients were diagnosed with CDAD(144 patients with hematologic disease;176with nonhematologic disease).The incidence of CDAD in patients with hematologic disease was estimated to be 36.7 cases/10000 patient hospital days,which was higher than the 5.4 cases/10000 patient hospital days in patients with nonhematologic disease.Recurrence of CDAD was more frequent in patients with hematologic disease compared to those with nonhematologic disease(18.8%vs 8.5%,P<0.01),which was associated with higher re-use of causative antibiotics for CDAD.Mortality due to CDAD did not differ between the two groups.Multivariate analysis showed that intravenous immunoglobulin was the only significant factor associated with a lower rate of recurrence of CDAD in patients with hematologic disease.CONCLUSION:The incidence and recurrence of CDAD was higher in patients with hematologic disease than in those with nonhematologic disease.

Recent advances in targeted endoscopic imaging:Early detection of gastrointestinal neoplasms

Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy.This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells.Molecular imaging has several advantages including minimal damage to tissues,repetitive visualization,and utility for conducting quantitative analyses.Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible.Molecular imaging during gastrointestinal endoscopy requires thedevelopment of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio.Additionally,a high-resolution endoscope with an accurate wide-field viewing capability must be developed.Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer.

Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis

BACKGROUND Fexuprazan,a novel potassium-competitive acid blocker,reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells.Fexuprazan’s suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner.AIM To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis(EE).METHODS Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks.The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8.The secondary endpoints included the healing rate of EE at week 4,symptom response,and quality of life assessment.Safety profiles and serum gastrin levels were compared between the groups.RESULTS Of the 263 randomized,218 completed the study per protocol(fexuprazan 40 mg,n=107;esomeprazole 40 mg,n=111).Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8[99.1%(106/107)vs 99.1%(110/111)].There were no between-group differences in the EE healing rate at week 4[90.3%(93/103)vs 88.5%(92/104)],symptom responses,and quality of life assessments.Additionally,serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups.CONCLUSION Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8.We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.