Advances in Digestive Medicine最新文献

We proposed that cancer stem cells (CSCs) survived and presented resistance to radiotherapy (RT) in hepatocellular carcinoma (HCC) cells. Interleukin 6 (IL-6) has been reported to be particularly involved in HCC tumorigenesis. Therefore, we intended to validate that IL-6 downstream STAT3-mediated CSCs formation and immune checkpoint PD-L1 expression in HCC, thus contributing to radioresistance. HBV-positive HCC tumorspheres were formed and exposed with X-ray irradiation, cell viability of which was measured consequently. Specific inhibitors targeting EGFR (by gefitinib), STAT3 (by BBI608), and HCC-targeted therapy sorafenib were investigated to suppress tumorsphere formation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used for detecting STAT3-downstream PD-L1 and anti-apoptosis MCL1 and BCL2 gene expression in the PLC5-derived tumorspheres and STAT3-knockdown PLC5. We found that RT significantly inhibited HBV-positive Hep3B and PLC5 cell viability but not for HCC-derived stem-like tumorspheres cultured by EGF, IL-6, bFGF, and HGF. It revealed that tumorspheres presented radioresistance compared with the parental cells. Specifically, RT induces IFNs, EGF, and IL-6 expression, resulting in STAT3 phosphorylation. Kaplan–Meier plotter indicated that highly EGF (p = .0024), IL-6 (p = .12), and FGF2 (p = .0041) were associated with poor survival probability in patients with HBV-positive HCC. We further demonstrated that BBI608 and sorafenib significantly suppressed PLC5 cell viability and PLC5-derived tumorsphere formation. To investigate the mechanism of CSC-presented radioresistance, STAT3 and STAT3-downstream genes, including PD-L1 and anti-apoptosis MCL1 and BCL2, were detected using qPCR. We demonstrated higher STAT3, PD-L1, MCL1, and BCL2 in Hep3B- and PLC5-derived CSCs compared to PLC5. In addition, knockdown of STAT3 reduced cell proliferation in PLC5 cells, resulting in down-regulation of IL-6-mediated PD-L1 and BCL-2. Meanwhile, we found that knockdown of STAT3 significantly improved RT-mediated suppression of tumorsphere formation. In conclusion, we found that CSCs presented radioresistance and figured out which may be mediated by STAT3 in HBV-positive HCC.

A 43-year-old woman presented with intermittent lower abdominal sharp pain for 4 months, which radiated to her back and right thigh, especially during menstrual period. She denied fever, weight loss, and change in bowel habits, hematochezia, or dysuria. Due to persistent symptoms, colonoscopy was arranged and showed two protruding lesions at the cecum (Figure 1A) and rectosigmoid junction (Figure 1B), respectively. Endoscopic ultrasound (EUS) was arranged for evaluating the originating layer and echogenicity. EUS with miniprobe showed one 25.7 × 9.6 mm heterogeneous hypoechoic mass outside cecum, which was adjacent to the serosa layer (Figure 1C), and one 22.5 × 9.5 mm homogenous hypoechoic mass arising from muscularis propria layer at the rectosigmoid junction (Figure 1D). The differential diagnosis included gastrointestinal stromal tumors, leiomyomas, and schwannomas, which originate from muscularis propria layer and presented as hypoechoic echogenicity.¹ Symptoms associated with menstrual cycle are an important diagnostic clue for endometriosis, which is detected as hypoechoic lesions on EUS. One 2 × 2 cm cystic lesion in the paracecal area and enlarged appendix were noted during laparoscopy (Figure 2A), and laparoscopic right hemicolectomy was performed due to the will of this patient. Pathological examination is compatible with endometriosis (Figure 2B). Dienogest was used for treatment of rectal endometriosis. The pain improved significantly after surgery and medical therapy.

Bowel endometriosis accounts for 3.8% to 37% of women with endometriosis and is most commonly involved in rectosigmoid colon, followed by ileocecal region, appendix and other parts of bowel.² Patients with bowel endometriosis may present with dysmenorrhea, infertility or gastrointestinal symptoms. Transvaginal ultrasound is the preferred modality for patients suspected of rectovaginal endometriosis, and EUS can discriminate the depth of infiltration and aids in surgical planning. Bowel endometriotic lesions involve the serosa, muscularis propria, submucosa, and mucosa layer in 94.5%, 95.1%, 37.8% and 6.4% of cases, respectively.³

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

The authors declare no conflicts of interest.

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

A 63-year-old female presented to our hospital for further management of a rectum lateral spreading lesion discovered by colonoscopy for fecal occult blood survey. Conventional white light colonoscopy showed type 0-IIa + IIb lesion over rectum (Figure 1A). Indigocamine chromoendoscopy showed an irregular mucosal surface pattern (Figure 1B). Subsequent magnifying colonoscopy with narrow-band imaging (NBI) revealed a focal avascular area with scant enlarged, dilated branch-like microvascular pattern on the lesion surface (Figure 1C). 12 MHz endoscopic ultrasound (EUS) showed thickening of mucosal layer (second layer) with preserved muscular propia layer (Figure 1D).

What is the diagnosis?

Biopsy specimen showed colon tissue with atypical lymphocytes proliferation above the lamina propria (Figure 2A–E). Immunohistochemical stain showed CK (scant lymphoepithelial lesions), CD138(−), MNDA focal positive, CD20(+), CD79a(+), and PAX-5(+). Mucosa-associated lymphoid tissue lymphoma (MALToma) is diagnosed.

Primary gastrointestinal non-Hodgkin lymphoma is most often located in the stomach. The large intestine MALToma is rare.¹ Primary colorectal lymphoma accounts for approximal 10% of gastrointestinal lymphoma and 0.2% of colorectal malignancy.² The gross morphology of colorectal lymphoma could be polyposis, subepithelial tumor, epithelial mass, and ulcerated type under white light endoscopy.³ However, flatten type may mimic lateral spreading tumor and be confused with sessile serrated lesion. Image-enhanced colonoscopy was useful for observed microstructure of flatten lesion. Tree-like-appearance blood vessels observed on magnified NBI have been mentioned in colon MALT lymphoma.⁴ In this case, Indogocarmine chromoendoscopy showed irregular mucosal surface pattern, not correlated with EUS finding. NBI magnifying colonoscopy showed Japan NBI Expert Team classification type 3 with branch-like microvascular pattern was the high spot and gave us the hint of colon MALToma.

The authors declare no conflicts of interest.

Informed consent was obtained from the patient to publish this article and images.

Thrombotic thrombocytopenic purpura (TTP) is an unusual disease with a 90% mortality rate without prompt management. The typical clinical manifestations include thrombocytopenia, hemolytic anemia, neurological symptoms, fever, and renal impairment. However, recognizing TTP in its early stages is not always easy due to limited clinical experience and sometimes atypical presentation. We report a 44-year-old male who initially suffered from jaundice and skin purpura, followed by epigastric pain. Acute pancreatitis was first suspected after a computerized tomography (CT) scan in the local medical department, without a definite etiology. He was then transferred to our hospital for further investigation of hemolysis. Transient neurological symptoms occurred 1 week after transferring. TTP was later confirmed based on schistocytes noted in peripheral blood smear and ADAMTS-13 activity = 0%. The patient was discharged successfully after prompt therapeutic plasma exchange and steroid treatment. We present the first case of TTP inducing acute pancreatitis in Asia and remind that acute pancreatitis is a possible cause of abdominal pain, although it's a rare manifestation of TTP.

Increased uptake of hepatitis C virus (HCV) treatment among people who inject drugs (PWID) is critical to achieve HCV elimination goals. This study attempted to observe the influence of different referral strategies among HCV-infected PWID for direct-acting antivirals (DAA). From January 2019 to November 2020, approximately 190 PWID regularly received opioid agonist therapies (OAT) in the drug addiction rehabilitation clinic of our institute. Among these, those with positive anti-HCV were further referred to our hepatology clinics for HCV viremia screening and treatment. According to physician involvement, referral strategies were divided into three models including patient self-intention referral (SR); intensive referral (IR) where patients were referred by clinicians; and fast-intensive referral (FIR) where patients were referred by clinicians with a fast-screening and easy-treatment program. A total of 121 HCV-infected PWID were enrolled and 71 (58.7%) of them received the referrals: 16 (22.5%) in the SR model, 36 (50.7%) in the IR model, and 19 (26.8%) in the FIR model. Monthly average referred patient number was 2.7 people in the SR model, 2.8 people in the IR model, and 4.8 people in the FIR model, respectively. Among the 71 referred patients, 64 (90.1%) had detectable HCV viremia with genotype distributions being genotype 1a (G1a) in 23 patients (35.9%), G1b in 10 (15.6%), G2 in 5 (7.8%), G3 in 6 (9.4%), and G6 in 20 (31.3%). Except for three patients who refused treatment, 61 patients underwent and completed DAA treatment including 35 patients for Maviret, 15 for Epclusa, 9 for Harvoni, and 2 for Zepatier. Excluding three patients who were lost to follow-up and one becoming reinfected, 57 (93.4%) eventually achieved a sustained virologic response. Although HCV treatment uptake among PWID in this hospital-based setting remained suboptimal, the FIR model with a quick-to-screen and easy-to-treat program was proven practicable in the hospital setting. Further innovative strategies are required to reach all HCV-infected PWID receiving OAT.

The prevalence and incidence of Crohn's disease (CD) in Asia is rising, and it is important to know the risk factors of mortality. In our study, CD patients diagnosed and treated in the Chang Gung Memorial Hospital Linkou branch were enrolled from January 1989 to October 2019. The collected data included age, sex, disease duration, location and behavior of the disease, biochemical parameters at admission, medication history, surgical history, and comorbidities. The mean age at diagnosis was 35.7 ± 16.1 years old and the male-to-female ratio was 2.4. The penetrating type of CD was the most common (41.3%) of disease behavior. The ileocolonic area is the most common location of disease involvement (79%). 7.7% of patients had low serum albumin levels (<3 g/dL). 16.8% of patients had hemoglobin levels less than 10 g/dL. Of the patients included, 4 died during the follow-up period. Low serum albumin levels at admission (p = .0307) are an independent predictor for mortality. In conclusion, it is important in perioperative care, especially for CD patients with hypoalbuminemia.

Primary hepatic angiosarcoma (PHA) accounts for 0.5% to 2% of all primary hepatic malignancies, and histopathology findings are required to diagnose PHA accurately. This study investigated 12 patients with PHA at a single medical center in southern Taiwan. We analyzed the clinical characteristics, imaging features, histopathology findings, and survival outcomes of patients with PHA. Of the 12 patients, abdominal pain and fullness were the most common symptoms, and their liver biochemistry data and tumor markers were mostly within the normal limits. The liver tumors tended to present as multifocal or diffuse nodules with bilobar involvement. The median overall survival (OS) of the 12 patients after diagnosis was 9 months. Improved OS was observed in the surgery group compared with the nonsurgery group (15 vs. 2 months, p = .003). The median OS of patients in the surgery ± systemic therapy group was superior to that of patients in the systemic therapy group and in the no-therapy groups (15 vs. 5 vs. 2 months, respectively; p = .012). Complete surgical resection remains the optimal treatment choice, and combined surgery and systemic therapy seem beneficial but require further investigation.

Chronic liver damages may end up with cirrhosis and portal hypertension, featured by splanchnic hyperdynamic circulation, angiogenesis, and collaterals formation. Melatonin is used to improve sleep quality, which exerts anti-inflammatory, anti-angiogenesis, and vascular actions without significant side effects. However, the relevant impacts on aforementioned derangements are unclear. Liver cirrhosis was induced by bile duct ligation in Sprague-Dawley rats. The rats received melatonin (40 mg/kg/day, i.p.) or vehicle for 28 days. Experiments were performed on the 28th day when cirrhosis developed. In cirrhotic rats, melatonin treatment significantly increased superior mesenteric artery resistance and reduced the blood flow. Melatonin enhanced the portosystemic collateral responsiveness to arginine vasopressin, reduced mesenteric vascular area, shunting degree, and down-regulated mesenteric MMP-2 protein expression. Melatonin improved the splanchnic hyperdynamic circulation, portosystemic collateral shunting, and mesenteric angiogenesis in cirrhotic rats. These beneficial effects make melatonin potentially feasible in clinical setting, but further investigation is required.

Chronic hepatitis B (CHB) is a progressive disease and leads to cirrhosis, cirrhotic complications, hepatocellular carcinoma (HCC), and death in a significant proportion of patients. Long-term treatment with nucleos(t)ide analogues (NUCs) significantly reduces the incidences of adverse liver-related events and improves survival in patients with CHB.¹ Although NUC therapy reduces the incidence of HCC, it does not completely eliminate this risk. Entecavir (ETV), tenfovir disoproxil fumarate (TDF), and tenofovir alafenamide are the recommended first-line NUCs for patients with CHB.¹ Whether the effectiveness for preventing HCC differs among these drugs remains unclear. Choi et al.² first reported that TDF treatment was associated with a significantly lower risk of HCC compared with ETV treatment in a population-based cohort, which was validated in a hospital-based cohort. Subsequently, some retrospective observational studies were conducted to compare the risk of HCC between patients treated with TDF versus those treated with ETV but contradictory results have been obtained.^3-7 As such, meta-analyses have been conducted to resolve the discrepancies.^3-7 Despite similar primary studies being included, the statistical significance of the difference between these two drugs varies among these meta-analyses, although more studies reported a lower risk of HCC with TDF treatment.^3-7 Furthermore, whether TDF treatment confers a lower risk of HCC in patients with cirrhosis than ETV treatment remains controversial.^{8, 9} The biological mechanisms underlying this differential effect remain unclear.

In this issue, Lin et al. compared the risk of HCC in a consecutive cohort of patients with hepatitis B virus (HBV)-related liver cirrhosis who received ETV (n = 198) versus TDF (n = 88) treatment.¹⁰ There were no significant differences in demographics or baseline characteristics between the ETV and TDF groups. During a median follow-up of 57.5 months, 25 (12.6%) patients in the ETV group developed HCC compared to 12 (13.6%) patients in the TDF group. The 5-year cumulative incidence of HCC was comparable between the ETV and TDF groups (6.57% vs. 9.09%, p = .242). They further calculated the standardized incidence ratios of HCC in both groups by comparing the observed incidence with that predicted by the REACH-B model. The observed incidence was not significantly different from the predicted incidence in either group. Multivariable Cox regression analysis identified age, male, diabetes, and platelet as the independent predictors for HCC development. They concluded that ETV and TDF provided comparable preventive effects on HCC development in patients with HBV-related liver cirrhosis.

Although ETV and TDF have been shown to reduce the risk of HCC