Advances in Digestive Medicine最新文献

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

Hepatitis B virus (HBV) is one of the most important causes of end-stage liver disease, including cirrhosis and hepatocellular carcinoma worldwide.¹ Taiwan is known to be hyperendemic for HBV infection. Although the implementation of nationwide universal hepatitis B vaccination program since 1984 significantly decreased the prevalence of chronic HBV infection from 10.9% to 0.5% in children,² the prevalence of seropositivity of hepatitis B surface antigen (HBsAg) in adults was still up to 13.7% in 2002.³ In addition to HBV, Taiwan is also threatened by other hepatitis viruses, including hepatitis A, C, D, and E viruses. Thus, patients with chronic HBV infection coinfected or superinfected with other hepatitis viruses are not uncommon. Among these viral hepatitis, hepatitis C virus (HCV) coinfection in HBV carriers is most common in Asia. Previous studies revealed that patients with HBV and HCV coinfection have a greater risk of developing cirrhosis and hepatocellular carcinoma, leading to a poorer outcome than those with HBV or HCV monoinfection.⁴ However, little is known about the clinical manifestations and long-term outcomes of HBV carriers with hepatitis A virus (HAV) and hepatitis D virus (HDV) coinfection or superinfection.

In this issue of the Advances in Digestive Medicine, Wu et al investigated whether prior exposure of HAV or HDV was associated with adverse long-term outcomes in patients with chronic HBV infection.⁵ Compared with HBV carriers without exposure to HAV or HDV, the risk of advanced liver disease increased by more than 10 times in patients with seropositivity of anti-HAV or anti-HDV. Their findings confirmed that the superinfection of other hepatitis virus in patients with chronic HBV infection will aggravate the underlying liver disease. However, several issues were worthy of discussion.

First, HAV is one of the most common etiologies of acute hepatitis worldwide.⁶ Because of poor sanitation and inadequate hygiene, the prevalence of HAV infection was high and most individuals infected with HAV in childhood before 1990 in Taiwan. The annual incidence of HAV infection dramatically decreased after improving sanitation conditions and providing HAV vaccination for high-risk children since 1995.⁷ Since then, the seroprevalence of anti-HAV continued to decline in Taiwan. The age-stratified seroprevalence of anti-HAV was lower than 5% in the younger population.⁸ In the current study of Wu et al, the anti-HAV seropositive rates were quite low in inactive carriers younger than 60 years old. The most worrisome thing is that the risk of a sudden outbreak of HAV infection in patients with chronic HBV infection may increase in the future. To avoid severe clinical course of HAV superinfection, HAV vaccination is recommended for p

Consistent high-quality of papers published in Advances in Digestive Medicine (AIDM) can only be maintained with the cooperation and dedication of a number of expert referees. The Editors would like to thank all those who have donated the hours necessary to review, evaluate and comment on manuscripts; their conscientious efforts have enabled the journal to maintain its tradition of excellence. We are grateful to the following reviewers for their contributions during 2021.

Chang, Chun-Chao

Chang, Chung-Yu

Chang, Jia-Jang

Chang, Li-Chun

Chang, Wei-Lun

Chen, Chien-Hung

Chen, Chien-Lin

Chen, Chih-Yen

Chen, Jiann-Hwa

Chen, Ming-Jen

Chen, Peng-Jen

Chen, Wen-Chi

Cheng, Hsiu-Chi

Cheng, Pin-Nan

Cheng, Yuan-Lung

Chiu, Han-Mo

Chou, Chu-Kuang

Chou, Jen-Wei

Chu, Yin-Yi

Chuah, Seng-Kee

Chuang, Chiao-Hsiung

Dai, Chia-Yen

Fang, Kuan-Chieh

Han, Ming-Lun

Hsieh, Ping-Hsin

Hsieh, Yu-Hsi

Hsu, Chao-Wei

Hsu, Ching-Sheng

Hsu, Ping-I

Hsu, Yao-Chun

Huang, Chien-Hao

Huang, Chung-Feng

Huang, Hui-Chun

Huang, Kuo-Hung

Huang, Yi-Hsiang

Huang, Tien-Yu

Hung, Chao-Hung

Jeng, Wen-Juei

Kao, Sung-Shuo

Kao, Wei-Yu

Kuo, Chao-Hung

Kuo, Yu-Ting

Lai, Hsueh-Chou

Lee, I-Cheng

Lee, Mei-Hsuan

Lee, Hsi-Chang

Li, Chung-Pin

Liang, Chih-Ming

Lin, Chih-Lin

Lin, Chih-Wen

Lin, Shyr-Yi

Lin, Hsiang-Hung

Lin, Tsung-Jung

Liou, Jyh-Ming

Lu, Hsiao-Sheng

Luo, Jiing-Chyuan

Sheu, Ming-Jen

Shih, Hsiang-Yao

Shiu, Sz-Iuan

Su, Tung-Hung

Sung, Kai-Feng

Tai, Wei-Chen

Tsai, Tzung-Jiun

Tsay, Feng-Woei

Tseng, Chih-Wei

Wang, Chia-Chi

Wang, Huay-Min

Wang, Wen-Lun

Wang, Yen-Po

Wu, I-Chen

Wu, Jeng-Yih

Yan, Sheng-Lei

Yang, Hung-Chih

Yang, Tsung-Chieh

Yeh, Hsing-Jung

Yen, Hsu-Heng

Yi, Chih-Hsun

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target downregulators of the anticancer immune response. ICIs have revolutionized the treatment of various malignancies. However, many immune-related adverse events have also been described, which mainly occurs when the immune system becomes less suppressed, and affects various organs, including the gastrointestinal tract. We report a case of atezolizumab-associated colitis with clinical and endoscopic follow-ups. The patient was a 72-year-old male diagnosed with advanced squamous cell lung cancer treated with atezolizumab and combination chemotherapy. Two months after atezolizumab therapy, bloody diarrhea and abdominal pain were reported. Initial colonoscopy revealed colonic ulcers with diffuse erythema and loss of vascularity. Histology demonstrated ulcerated mucosa with acute inflammation. Steroids were promptly indicated due to suspicion of immune-related colitis caused by atezolizumab. Follow-up sigmoidoscopy performed 6 weeks after initiating steroid therapy showed improvement of inflammation. Histological findings revealed eroded colonic mucosa with abortive crypts, lymphoplasma, and eosinophil cell infiltration, which mimicked inflammatory bowel disease (IBD). However, there was no colitis relapse after steroid discontinuation. The case demonstrated endoscopic and histological presentations of immune-mediated colitis that mimicked IBD.