Advances in Digestive Medicine最新文献

Melanosis coli, a dark brown discoloration of the colonic mucosa, is associated with chronic use of anthraquinone laxatives (senna). In addition, Aloe Vera¹ and Rhubarb,² used in traditional alternative medicine in Taiwan, are also implicated as the causes of melanosis coli. The term “melanosis,” however, may be misleading, since the pigment responsible for the discoloration is not the deposition of melanin but of lipofuscin in macrophages in the colonic lamina propria. Anthroquinone laxatives induce apoptosis of colon epithelium cells, which are ingested by adjacent macrophages within the mucosa. Those macrophages migrate to the lamina propria and convert the apoptotic cells into lipofuscin with lysozyme. Interestingly, adenomas have impaired absorption of apoptotic debris into the macrophages³ and thus stand out in the dark mucosa of the melanosis coli as a “pigmentation sparring sign.”

Whether melanosis coli increases the risk of colon adenoma and adenocarcinoma is controversial. An early prospective case-control study by Siegers et al suggested anthraquinone laxative abuse was associated with a relative risk of 3.04 (95% confidence interval [CI]: 1.18–4.90) for colorectal cancer.⁴ Most recent case-control studies, however, showed that melanosis coli was associated with increased detection of adenomas but not adenocarcinomas. Kassim et al found that patients with melanosis coli were more likely to have both hyperplastic polyp and low-grade adenoma, but not adenocarcinoma.⁵ Liu et al found that melanosis coli was associated with higher detection rates of low-grade adenoma (odds ratio [OR] = 1.54; 95% CI: 1.06–2.23; P < .05) but similar detection of high-grade adenomas or adenocarcinomas.⁶ Blackett et al showed patients with melanosis were more likely to have an adenoma ≤5 mm (OR = 1.62; 95% CI: 1.04–2.51; P = .03) but not adenomas 6 to 9 mm or ≥10 mm.⁷ Abu Baker et al even reported that melanosis coli was associated with less diagnosis of adenocarcinoma than controls (0.3% vs 3.9%; P < .001).⁸ Katsumata et al conducted a case-control study in Japan and performed a meta-analysis of five studies at the same time. They concluded that although hyperplastic polyps and adenomas were more frequently detected in patients with melanosis coli, the risk of colorectal cancer was not increased.⁹

There are two plausible explanations for the association between melanosis coli and increased detection of adenomas: either melanosis coli promotes the development of adenoma or it facilitates the detection of adenoma. The lack of association between melanosis coli and adenocarcinoma lends support to the latter assumption, as, in accordance with the theory of the colorectal adenoma-carcinoma sequence, increased d

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 2022.

Chang, Chen-Wang

Chang, Li-Chun

Chang, Tien-En

Chang, Wei-Yuan

Chen, Chieh-Chang

Chen, Chiung-Yu

Chen, Jiann-Hwa

Chen, Kuan-Chih

Chen, Peng-Jen

Chen, Yu-Jen

Cheng, Pin-Nan

Chi, Chen-Ta

Chien, Hsi-Yuan

Chou, Chu-Kuang

Chu, Cheng-Hsin

Chuah, Seng-Kee

Chuang, Chiao-Hsiung

Chung, Chen-Shuan

Elsherbiny, Nehal M.

Hsieh, Ming-Tsung

Hsieh, Sen-Yung

Hsieh, Yu-Hsi

Hsu, Chao-Wen

Hsu, Wen-Feng

Hsu, Wen-Hung

Huang, Chung-Feng

Huang, Tien-Yu

Huang, Yi-Hsiang

Hung, Chih-Sheng

Jeng, Wen-Juei

Kao, Sung-Shuo

Kawamura, Junichiro

Kuo, Yu-Ting

Le, Puo-Hsien

Lee, I-Cheng

Lee, Kuei-Chuan

Lee, Pei-Chang

Liang, Chih-Ming

Liao, Szu-Chia

Liao, Wei-Chih

Lin, Wey-Ran

Lin, Xi-Hsuan

Lin, Yu-Min

Liou, Jyh-Ming

Liu, Chen-Hua

Liu, Nai-Jen

Luo, Jiing-Chyuan

Nishimura, Takeshi

Peng, Cheng-Yuan

Peng, Yen-Chun

Shieh, Tze-Yu

Shiu, Sz-Iuan

Su, Chien-Wei

Tai, Wei-Chen

Tsai, Kun-Feng

Tsai, Ming-Chang

Tsai, Tzung-Jiun

Tseng, Chih-Wei

Tseng, Ping-Huei

Tsou, Yung-Kuan

Wang, Yen-Po

Wu, Keng-Liang

Wu, Pei-Shan

Yadegar, Abbas

Yang, Hung-Chih

Yang, Tsung-Chieh

Yen, Hsu-Heng

Yu, Ming-Lung

A 61-year-old woman with underlying disease of hypertension, type II diabetes mellitus, and newly diagnosed lung adenocarcinoma visited our outpatient department because of general fatigue with body weight loss for 2 months. Panendoscopy for anemia showed a patch-like lesion at the great curvature of the middle body (Figure 1A, arrows). Using narrow band image, there was no significant irregular vascularity, but with clear demarcation of the lesion (Figure 1B, arrows).

What is your impression for this patient?

1.  Gastric cancer

2.  Gastric intestinal stromal tumor

3.  Gastric metastasis

4.  Erosive gastritis

Pathology of tissue biopsy revealed gastric mucosa infiltrated by angulated atypical glands composed of cells with large and hyperchromatic nuclei (Figure 2A, arrow). The immunohistochemical stain demonstrated strong positive for cytokeratin (CK), cytokeratin 7 (CK7) and thyroid transcription factor-1 (TTF-1) (Figure 2B), and negative for cytomegalovirus (CMV), and cytokeratin 20 (CK20). It was diagnosed to be a lung cancer with gastric metastasis.

The incidence of lung cancer is the highest in the global world.¹ However, the gastrointestinal metastasis with mucosal invasion is rare, and has extremely variable morphology. Therefore, a cauliflower-like patch should be a differential diagnosis of gastric metastasis.

The authors declare no conflicts of interest.

The study complies with current ethical considerations, and an informed consent was signed by the patient.

Hepatocellular carcinoma (HCC) represents one of the most prevalent and lethal type of malignancies around the globe. Despite the advancement in medical research and therapeutics development, HCC still remains a taunting challenge in clinical settings. Recent studies indicate that the presence of cancer stem cells (CSCs) may be the underlying factor for treatment failure, distant metastasis, and disease recurrence. Elevated stemness gene expression has been correlated to disease stage and poorer prognosis in HCC patients. Initially, we established that β-catenin is highly expressed in HCC clinical samples. We subsequently re-validated the idea that CD133+/CD90+ subpopulation cells exhibited CSCs properties including elevated stemness expression (β-catenin, Nanog, c-Myc, and Twist1), increased self-renewal capacity and metastatic potential. Using this cell model, we tested the potential anti-CSCs effects of phenethyl isothiocynanate (PEITC), a phytochemical isolated from cruciferous vegetables. Treatment of PEITC led to a decreased percentage of CD133+/CD90+ cells in both Huh7 and Sk-Hep1 cell lines. In addition, PEITC suppressed stemness gene expression, self-renewal ability, and metastatic potential in HCC CSCs. Mechanistically, PEITC conveyed its anti-CSCs effects via upregulating microRNA-214, a negative regulator of β-catenin. In conclusion, we provided evidence that PEITC could suppress HCC CSCs generation/maintenance. With further clinical testing, PEITC could be used either alone or in combination with currently available chemotherapeutic agents to achieve improved efficacy.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder characterized by relapsing inflammation and severe mucosal damage in the intestine. Young IBD women are often worried about their fertility, the disease activity during pregnancy, the heritability of the disease to their unborn child, and also the effect of their disease on the pregnancy itself. The pregnancy outcome and drug usage during pregnancy are rarely discussed in an area of low IBD prevalence. To evaluate (a) decision-making around drug therapy during pregnancy and (b) the prognosis for pregnant IBD patients in an area of low IBD prevalence. We conducted a retrospective analysis across seven medical centers in Taiwan from February 2009 to February 2019. Maternal and fetal/neonatal outcomes were analyzed. A total of 17 patients (21 pregnancies) were enrolled. The mean age of patients was 35.9 ± 4.6 years. Six patients (35.3%) had fertility worries and two (11.8%) had infertility. Five patients had Crohn's disease (CD), of whom 60% had undergone prior abdominal surgery. The remaining 12 patients had ulcerative colitis (UC), of whom 8.3% had undergone prior abdominal surgery (significantly lower than CD patients [P = .02]). There were no significant differences between the CD and UC groups in terms of age, age of primigravida, height, weight, fertility worries, or infertility. Abortion, miscarriage, or stillbirth was seen in 23.8% of patients, and 14.3% of patients needed treatment to prevent miscarriage. Low birth weight (<2500 g) was seen in 14.3% of births, and 14.3% had associated complications. There was no significant difference between CD and UC patients in terms of pregnancy outcome. During pregnancy, 33.3% of patients changed their drug regimens, stopping the use of 5-ASA (9.5%), immunosuppressants (4.8%), corticosteroids (4.8%), or biologics (9.5%). However, if IBD progressed during pregnancy, corticosteroids were considered (19.4%) for disease control. These are real-world experiences of IBD during pregnancy in Taiwan. High rates of abortion, miscarriage, or stillbirth and treatment to prevent miscarriage were noted. Among all subjects, 33.3% of patients changed their drug regimen during pregnancy. Corticosteroids were also considered if IBD progressed during pregnancy in this study.

A 69-year-old man with alcohol use disorder presented with tarry stools for 1 week. Upon presenting at the hospital, his hemoglobin level was 4.3 g/dL (normal range: 13–18 g/dL). Esophagogastroduodenoscopy revealed a firm, dark-brown, irregularly island-like mass (around 3 cm) on a clean-based ulcer, with no active bleeding, on the anterior wall of the duodenal bulb (Figure 1A). Abdominal computed tomography of the duodenal lesion showed a 6.5 cm mass in the hepatic hilum with a satellite mass infiltrating the proximal duodenum (Figure 2). Histopathology of the lesion showed tumor elements that were weakly positive on α-fetoprotein immunostaining; thus, indicating a moderate differentiation of hepatocellular carcinoma (HCC). A few days later, the patient presented with recurrent gastrointestinal bleeding and underwent endoscopic argon plasma coagulation (ERBE Elektromedizin GmbH, Germany, VIO 200D; forced mode, gas flow 1.8 L/min, power setting 30 W) with an axial probe (2.3 mm in diameter, 220 cm in length) (Figure 1B), with a subsequent transcatheter arterial embolization. Temporary hemostasis was achieved; unfortunately, he died of tumor progression and persistent duodenal bleeding 2 months later.

Extrahepatic metastases of HCC have been reported mainly in the lung and in regional lymph nodes, while direct invasion into the gastrointestinal tract is rare (0.5%–2% of the cases)¹ and is generally associated with advanced disease (with a large tumor >5 cm).² In these cases, the stomach and duodenum are the most frequent sites of direct invasion and commonly present with bleeding and gastric outlet obstruction. The first line of treatment for such cases would be a surgical resection with a pancreas-sparing duodenectomy.³ Other treatment approaches include external beam radiation therapy, transcatheter arterial embolization, and a local injection with an ethanol injection. However, attempts to control tumor bleeding often fail, and the prognosis of HCC with duodenal invasion is poor. Liang et al. reported that 50% of patients with duodenal invasion died within 3 months.⁴ If endoscopic findings reveal an infiltrating mass into the duodenal bulb, it should raise suspicions of direct invasion by a liver tumor (Table S1).

All authors declare no conflicts of interest.

Informed consent was obtained from all participating adult subjects, together with the manner in which informed consent was obtained (ie, oral or written).

The prevalence of periampullary diverticulum (PAD) is relatively high in patients who undergo endoscopic retrograde cholangiopancreatography (ERCP). It is currently unclear if the presence of PAD impacts the success, difficulty, and complication rates of ERCP. The aim of the study is to investigate and compare the success rate, procedure difficulty, and complication rate between patients with or without PAD. Patients with PAD were further analyzed according to location and size. A total of 548 ERCP procedures were performed at our endoscopy center from 2015 to 2016. Those patients with previous ERCP, inability to locate the ampulla or abandoned procedure were excluded. 357 procedures were analyzed. A t test (normally distributed) or Mann-Whitney U test (skewed) for continuous data and chi-square or fisher's exact test for categorical data. A total of 116 were found to have PAD. The ampulla was located within the diverticulum in 8.9%, on the edge in 38.9%, and near in 52.2%. 64.3% of the PAD was large and 35.7% small. Patients with PAD were significantly older (P < .001) and more likely to undergo ERCP for common bile duct stone (P = .007). There was no difference in ERCP grade, cannulation difficulty, cannulation success, procedure time, and complication rate between the two groups. Location and size of PAD also did not impact ERCP. The presence of PAD did not affect ERCP cannulation rates, increase the difficulty of cannulation or caused more complications.

Sung, K-Y, Lu, C-L, Wang, Y-P. An unusual cause of obscure gastrointestinal bleeding. Adv Dig Med. 2022; 9:203-204.

Additional funding information details should be added on both Funding Information and Acknowledgment sections respectively. These should have read:

1. Funding information.

Taipei Veterans General Hospital, Grant/Award Number: V109-B-041, V111C-207; Taiwan Ministry of Science and Technology, Grant/Award Number: MOST 111-2628-B-075-011.

2. Acknowledgments.

The case report was supported by grants from the Taipei Veterans General Hospital (V109-B-041, V111C-207) and Taiwan Ministry of Science and Technology (MOST 111-2628-B-075-011).

We apologize for these errors.

Here, we present the case of an 87-year-old woman with heart failure, hypertension, and iron deficiency anemia with a treatment history of amlodipine, olmesartan, carvedilol, and hydralazine for 4 years, and ferrous sodium citrate for 2 years. The patient was referred to the Department of Gastroenterology for occult blood in stool, and endoscopic examination was arranged. Colonoscopy showed sigmoid colon adenocarcinoma, and esophagogastroduodenoscopy revealed speckled black pigmentation distributed from the duodenal bulb to the duodenal second portion (Figure 1). Histopathology revealed macrophages in the lamina propria containing pigmented granules negative for Prussian blue stain (Figure 2). The final diagnosis was pseudomelanosis duodeni.

Pseudomelanosis duodeni, characterized by brown to black spotty pigmentation in the duodenal bulb and the second portion on esophagogastroduodenoscopy,^1-3 was first described in 1976 by Bisordi and Kleinman.⁴ It occurs more commonly in older women.³ The pathogenesis is distinct from melanosis coli and remains poorly understood.¹ Previous studies have shown association with diabetes mellitus, hypertension, renal disease, folate deficiency, gastrointestinal bleeding, and ingestion of food or oral agents containing iron and sulfur.^1-3 Thus, one hypothesis implicates the accumulation of iron and sulfur in the duodenal mucosa caused by drugs (eg, hydralazine, furosemide, and hydrochlorothiazide) and food absorption, microhemorrhages, or reduced sulfur clearance due to decreased renal function.¹ Usually, this is an incidental finding without obvious clinical symptoms. Microscopically, the pigmented granules are found in the macrophages located in the lamina propria.^{1, 3} Although all pseudomelanosis duodeni contains an iron component, Prussian blue stain can still sometimes be negative, possibly because the iron pigments are in a sulfide form, and do not react with Prussian blue staining reagents.⁵ Pseudomelanosis duodeni should be distinguished from metastatic malignant melanoma as it is a benign condition with no evidence of malignant transformation in the future.^1-3 Further investigation or management are not required.

All authors contribute to all stages of article composition: data acquisition and editing, manuscript drafting, and manuscript revision.

The authors declare no conflict of interest.

The patient authorized the publication of the data and the patient's anonymity is preserved in the article.

Endoscopic submucosal dissection (ESD) achieves higher en bloc resection rates than endoscopic mucosal resection in early colorectal neoplasms. However, perforation occurs more frequently during ESD. We aimed to identify the risk factors for perforation during colorectal ESD. A total of 161 patients treated with colorectal ESD at a tertiary center between January 2014 and December 2019 were enrolled in this retrospective study. Perforation was defined as a deep defect of the muscularis propria, with or without direct contact with connective tissue outside the colon. Clinical risk factors for perforation during ESD, including age, sex, tumor morphology, tumor size, tumor location, procedure time, en bloc resection rate, histology, and submucosal fibrosis, were analyzed. The mean size of the ESD specimens was 38.2 ± 24.6 mm. The overall en bloc resection rate was 98.1%. Perforations occurred during ESD in 31 out of 161 patients (19.3%). All perforations were successfully treated with endoscopic closure using the hemoclips and nonsurgical management. Emergency surgery was not required in our patients. On multivariate analysis, severe submucosal fibrosis (odds ratio [OR] 3.06; 95% confidence interval [CI] 1.23-7.59; P = .016) and location in the right colon (OR 4.54; 95% CI 1.31-15.79; P = .017) were independent risk factors. Perforation during colorectal ESD occurred in 31 patients (19.3%), but all patients had a good outcome without surgery. Submucosal fibrosis and its location are risk factors for perforation during ESD.