Advances in Digestive Medicine最新文献

Since the advent of endoscopic sphincterotomy, developed in Japan and Germany in 1974, it has become a very common technique used for the treatment of a wide variety of conditions of the biliary system. However, because of the risk of adverse events associated with endoscopic retrograde cholangiopancreatography (ERCP)-guided treatment of bile duct stones, it is important to identify appropriate candidates for this procedure and reserve biliary endoscopy for patients with the highest probability of intraductal stones.

The prevalence of common bile duct (CBD) stones is reported to be 5% to 15% in patients undergoing elective cholecystectomy for symptomatic, uncomplicated cholelithiasis.^1-3 Liver biochemical tests may be most useful in excluding the presence of CBD stones. The negative predictive value of a normal liver function test in a series of more than 1000 patients undergoing laparoscopic cholecystectomy was over 97%, whereas the positive predictive value of any abnormal liver biochemical test was only 15%.⁴ The role of endoscopy in the evaluation of suspected choledocholithiasis, a guideline statement developed by the Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) in 2010, proposed a strategy to assign the risk of choledocholithiasis in patients with symptomatic cholelithiasis based on clinical predictors.⁵ The very strong predictors (major criteria) include CBD stones found on transabdominal ultrasound (US) study, clinical cholangitis, and total bilirubin level >4 mg/dL. The strong predictors (minor criteria) are dilated CBD on US (>6 mm with gallbladder in situ) or total bilirubin level 1.8 to 4 mg/dL. Patients with one major or two minor predictors are considered high risk and should receive preoperative ERCP. However, if patients have intermediate risk, they should undergo endoscopic ultrasonography (EUS) or magnetic resonance cholangiopancreatography (MRCP) examination before surgery to detect the presence of CBD stones. Two years earlier, ASGE released new guidelines for choledocholithiasis management.⁶ Emphasis was increased on using laboratory results and bile duct diameter in deciding when to perform ERCP. We noticed that there was no additional new definition of risk predictors in comparison to 2010. However, in the 2019 guidelines, new criterion requiring both bilirubin >4 mg/dL and biliary dilatation was added, which has a specificity approaching 90%. This is similar to the other two high-risk predictors, cholangitis and bile duct stones on imaging, both of which have a specificity exceeding 90%.⁷ Likewise, computed tomography (CT) is not included in the diagnostic algorithm if CBD stones are diagnosed based on US, liver function test, and clinical information. Most of the invisible CBD stones are small (<5 mm) or less calcified; therefore, they

Acute cholangitis has been reported as an uncommon adverse event after self-expandable metallic stent (SEMS) implantation. Herein, we report a case of an acute cholangitis caused by duodenal refluxate without duodenal obstruction. A 62-year-old woman received SEMS for an obstructive jaundice caused by a pancreatic head adenocarcinoma. She had been in stable condition until her percutaneous transhepatic cholangial drainage (PTCD) was clamped on the second postoperative day, and when a high fever and severe right epigastric pain developed. Fecal-impacted bowel loops were found through abdominal X-rays, and food contents were drained from PTCD afterward. Acute cholangitis caused by SEMS migration was initially suspected, and SEMS revision was performed two times, which did not improve the chymus reflux from PTCD. Metoclopramide was given after the second SEMS revision, and post-procedural upper gastrointestinal series with urografin shows no duodenal obstruction. No febrile event has been noted since the administration of metoclopramide. Acute cholangitis after SEMS implantation without duodenal obstruction could develop in patient with moderate to severe constipation. Prompt post-procedural prophylactic prokinetics for few days may prevent such episodes.

Liver cancer has a significant impact on global health. Taiwan is a country with a high incidence rate of liver cancer. Efforts in primary prevention and treatment of chronic hepatitis B and C are projected to decrease the liver cancer incidence in Taiwan. We used the Taiwan Cancer Registry data to explore the time trend of liver cancer incidence over the last decade, which showed a decreasing trend of 21% in males and 26.1% in females from 2009 to 2018. Both genders aged 30-39 years had the greatest decrease in liver cancer incidence, while those >70 years old had the least decrease. Our study also showed gender disparity in liver cancer with a persistent male predominance over time. In the past decade, the liver cancer incidence had a 2.5 to 2.7 sex ratio (male to female) and varied gender differences at different ages. Sex ratios peaked at age 40-49 years and gradually decreased as age increases. The pattern of age-specific gender differences was similar between 2009 and 2018. This finding implies that female sex hormones may play a protective role in the development of liver cancer.

The serum level of Mac-2 binding protein glycosylation isomer (M2BPGi) has been found to increase with the severity of liver fibrosis in biopsy-proved nonalcoholic fatty liver disease (NAFLD). However, the comparison of M2BPGi with noninvasive fibrosis markers such as AST to platelet ratio index (APRI), Fibrosis 4 Score (FIB-4), and NAFLD fibrosis score (NFS) in NAFLD patients remains unclear. The participants of Tzu Chi NAFLD cohort (TCNC) including health controls or NAFLD patients were enrolled in Taipei Tzu Chi Hospital. NAFLD was defined as fatty liver in imaging without hepatitis B virus (HBV), hepatitis C virus (HCV), drug, alcohol, or other known causes of chronic liver disease. A total of 777 subjects were included for final analysis. The serum levels of M2BPGi correlated with APRI, FIB-4 score, and NFS, respectively (P < .001). Of them, 376 (48.4%) were NAFLD patients and 401 were healthy controls. In the group of health controls or NAFLD patients, the M2BPGi levels were significantly higher in female subjects than those of male subjects (P = .027 and 0.006, respectively). Categorized by age, the levels of M2BPGi were significantly higher in elder age groups either in healthy controls or NAFLD patients (P < .05). Compared with healthy controls, NAFLD patients had significantly higher levels of BMI, waist circumference, metabolic components, and liver fibrosis markers such as APRI, NFS, and M2BPGi (P < .05), but no difference in FIB-4 score (P = .685). According to FIB-4 score, “intermediate- or high-risk group” had higher APRI, NFS, and M2BPGi than low-risk group. The serum M2BPGi levels correlated with three noninvasive biomarkers of liver fibrosis including APRI, FIB-4 score, and NFS. They were significantly higher in female or elder population. Furthermore, APRI, NFS, and M2BPGi were different between NAFLD patients and healthy controls, but no FIB-4 score. According to FIB-4 score to determine the risk of liver fibrosis, APRI, NFS, and M2BPGi were also different between low risk and “intermediate or high risk” of NAFLD patients, suggesting a surrogate marker for assessing liver fibrosis of NAFLD patients.

The hepatitis C virus core antigen (HCV-cAg) assay is a cheap and rapid alternative to HCV-RNA detection, while the results were limited to 12 weeks following direct-acting antiviral (DAA) treatment. In this study we aimed to investigate the role of the HCV-cAg assay up to 48 weeks after DAA treatment. We enrolled 98 patients with chronic HCV infection who received DAA treatment in this study. Plasma samples were assessed for HCV-RNA (AmpliPrep/COBAS TaqMan assay, Roche) and HCV-cAg (Abbott ARCHITECT HCV-cAg assay) levels at baseline, 12 weeks (P12) and 48 weeks (P48) after DAA treatment. The sensitivity and specificity of HCV-cAg were compared with those of HCV-RNA. A total of 284 samples from 98 enrolled participants were analyzed. HCV-cAg levels changed in parallel with HCV-RNA levels in HCV-infected patients during and after DAA therapy. HCV-cAg levels showed excellent correlation with HCV viral load (R = 0.951, R² = 0.905, β = 0.951, and P < .001). The overall sensitivity and specificity for HCV-cAg in detecting quantifiable HCV-RNA thresholds were 96.9% and 100%, respectively. Three patients with baseline HCV viremia had nonreactive HCV-cAg (false-negative rate was 1.02%); none of the patients were HCV-cAg positive and HCV-RNA negative. At 48 weeks after DAA treatment, the HCV-cAg assay detected all patients with viremia, demonstrating 100% sensitivity and specificity. In conclusions, the HCV-cAg assay has high sensitivity and specificity for the detection of pre- and post-DAA treatment viremia and may be a useful tool to confirm viremia at P12 and P48.

The presence of a bird feather as a foreign object inside the human body has rarely been reported in the literature. A feather can cause severe complications such as neck infection or duodenal perforation. Early recognition and treatment of this condition may prevent associated morbidity and mortality. We report a case of a female patient who had a feather inside her bile duct. The feather caused abdominal pain without acute cholangitis. Fortunately, it was successfully removed before causing severe complications. This is the first-ever case report of the migration of a feather into the common bile duct. A 54-year-old Taiwanese woman had a history of cholecystectomy due to acute calculous cholecystitis 1 year prior to this visit. She had also undergone endoscopic retrograde cholangiopancreatography (ERCP) two times due to acute cholangitis (8 years ago and 1 year ago). Endoscopic papilla sphincterotomy had been performed during ERCP for stone extraction. This time, she visited our clinic due to intermittent epigastric pain for 2 weeks. There were no signs of acute cholangitis. Abdominal computed tomography (CT) did not reveal bile duct stone or foreign bodies. ERCP was arranged for possible hidden stones not detected by CT. To our surprise, we pulled a 5-cm-long bird feather out of her bile duct during ERCP. After successfully removing the feather, she remained free of abdominal pain and other complications during the next 6 months of follow-up at our outpatient clinic. Migration of foreign bodies into the bile duct should be included in the differential diagnosis for unexplained abdominal pain in patients with choledochoduodenal fistula due to previous endoscopic papilla sphincterotomy.

Amyloidosis is defined as an excess extracellular deposit of protein fibrils, an associated syndrome with tissue injury and dysfunction. Light chain (AL) amyloidosis is the most common type of systemic amyloidosis. The most frequently involved organs are the kidneys, heart, liver, autonomous nervous system, and gastrointestinal tract. Systemic AL amyloidosis patients often have GI symptoms such as diarrhea and vomiting. Furthermore, asymptomatic gastric amyloid deposits are commonly found in patients with systemic AL amyloidosis. The clinical manifestations, laboratory results, and treatment of an 80-year-old female patient with AL amyloidosis of the gastrointestinal tract in our hospital were summarized. Relevant literatures on the etiology, clinical features, diagnosis, treatment, and prognosis of this disease were reviewed. The patient was referred to upper endoscopy because of melena for weeks. Large areas of irregular thickened gastric folds with overlying ulcers and friable polypoid masses at the fundus were seen, showing amyloid depositions. Further workup revealed that no involvement of other organs. Serum immunoelectrophoresis and bone marrow biopsy confirmed multiple myeloma, which was clinically thought to cause gastric amyloidosis. The patient was treated with melphalan, prednisolone, and thalidomide. After treatment, the melena was improved, the flattening gastric mass and a reduction in the serum kappa light chain level and kappa/lambda ratio were observed. Gastric amyloidosis is rarely seen at upper endoscopy in patients without a previously established diagnosis of myeloma. Early detection of gastrointestinal amyloidosis will ultimately improve the outcomes of patients with the rare disease.

Patients suffering from appendicitis with severe pathological findings or microperforation have a poor prognosis. Therefore, when selecting treatments, it is critical to clarify the factors related to histopathological severity and the presence of microperforation in cases diagnosed as mild appendicitis. We retrospectively collected data from 357 consecutive patients diagnosed with acute appendicitis based on symptoms such as fever, physical findings, blood tests, and imaging findings who underwent surgery at the Higashiosaka City Medical Center between January 2016 and December 2020. We investigated the predictors of pathological severity and the presence or absence of microperforations. Of the 335 patients, 252 (75%) had clinically mild appendicitis. In the multivariate analysis, diameter of the appendix ≥10.9 mm (P = .0013) and C-reactive protein ≥5.0 mg/dl (P = .0011) were related to gangrenous appendicitis, with odds ratios of 2.67 (95% confidence interval: 1.23-5.80) and 3.88 (95% confidence interval: 1.71-8.77), respectively. On the other hand, the presence of an appendicolith (P = .0083) and duration from onset to surgery ≥2 days (P = .0033) were related to microperforation, with odds ratios of 6.82 (95% confidence interval: 1.64-28.4) and 3.73 (95% confidence interval: 1.21-12.4), respectively. Patients with gangrenous appendicitis or microperforation had higher rates of postoperative complications, including more cases of Clavien-Dindo classification III and longer hospital stays (P < .05). Even in cases of clinically mild appendicitis, there is a possibility of microperforation or gangrenous appendicitis. Therefore, it is essential to carefully select the treatment in cases with more than 2 days after symptom onset, a dilated appendix, and an appendicolith.

Worldwide, colorectal cancer (CRC) is the most lethal and prevalent malignancy and was responsible for nearly 881 000 cancer-related deaths in 2018.¹ Despite the pathophysiologic mechanism of CRC being more complex than beyond thought, recent advances in the treatment of CRC provided more strategies, but the results were not satisfactory. In this issue, a study from Lin et al, reported that five STAT3-downstream genes were over-expressed in CRC-derived tumorspheres, including BHLHE40, ATF3, ERRFI1, ITPKA, and S100A14. As expected, the authors found that knockdown of STAT3 diminished the cell viability in HT29 cells in vitro since STAT3 was believed to involve in the initiation of cancer stemness property and progression. Therefore, these STAT3-downstream genes may contribute to cell proliferation and survival.

For the treatment of CRC, it is more complex. Ideally, the treatment goal is to remove the tumor as completely as possible, either at primary or metastatic sites, which mostly requires surgery. However, surgical intervention is limited to patients with resectable lesions and tolerant to surgery. Otherwise, tumor shrinkage and down-stage by radiotherapy and/or chemotherapy as neoadjuvant or adjuvant treatment are the leading options in the junction of surgically unresectable and intolerable patients. In recent decades, research studies demonstrated combination chemotherapy including FOLFOX (5-FU + OX), FOXFIRI (5-FU + IRI), XELOX or CAPOX (CAP + OX), and CAPIRI (CAP + OX) in CRC patients had prolonged their overall survival (OS) up to 20 months, especially those with metastases.² Nonetheless, the response results of chemotherapy in survival were not satisfactory, therapy targeting the CRC initiation, progression, and migration pathways became approaches to reinforce chemotherapy. In 1995, the first monoclonal antibody targeting EGFR-mediated pathways, named cetuximab, targeted to EGFR with convincing preclinical data were announced.³ Combinations of cetuximab with other existing chemotherapies also displayed promising results. The phase III CRYSTAL trial found that cetuximab plus FOLFIRI had better progression control (8.9 vs 8 months, hazard ratio [HR] 0.85; P = .048) than FOLFIRI alone.³ Another landmark trials, AVF2107 trial based on antiangiogenic therapy by a humanized IgG monoclonal antibody targeted to VEGF-A, named bevacizumab, for CRC improved both progression-free survival (PFS) and OS in metastatic CRC (RR: 44% vs 34.8%; OS: 20.3 vs 15.6 months; HR: 0.66, P < .001; PFS: 10.6 vs 6.2 months; HR: 0.54; P < .001).⁵ Several agents targeting various pathways such as BRAF inhibitor/MEK inhibitor, human epidermal growth factor receptor (HER)2 inhibitor, hepatocyte growth factor (HGF), and the receptor tyrosine kinase known as mesenchymal-epithelial transition factor (c-MET or MET) were