Posttreatment liver function, but not baseline liver function stratifies patient survival after direct-acting antiviral treatment in decompensated cirrhosis with hepatitis C virus.

BACKGROUND: The prognosis of cirrhosis is clearly stratified by liver function. Although direct-acting antiviral (DAA) has recently been used to eliminate hepatitis C virus (HCV), it is not clear whether liver function stratifies the prognosis of decompensated cirrhotic patients treated with DAA. METHODS: A total of 206 HCV-associated decompensated cirrhotic patients who started DAA from February 2019 to December 2021 at 31 Japanese hospitals were prospectively registered. RESULTS: The median age was 68, and the proportions of patients with Child-Pugh class A (CP-A), CP-B and CP-C were 10% (20/206), 76% (156/206) and 15% (30/206), respectively. Twenty-six patients died, and two patients underwent liver transplantation (LT); the 2- and 3-year LT-free survival rates were 90.0% and 83.2%, respectively. We examined factors associated with LT-free survival using 2 models including either CP class (Model 1) or MELD score (Model 2). In multivariate Cox proportional hazard analysis, CP class at 12 weeks after the end of treatment (EOT) in Model 1 and MELD score at 12 weeks after the EOT in Model 2 were significant factors, while baseline CP class or MELD score was not. Two-year LT-free survival rates were 100%, 91.6% and 60.4% for patients with CP-A, CP-B and CP-C at 12 weeks after the EOT and 95.2% and 69.6% for patients with MELD < 15 and MELD ≥ 15 at 12 weeks after the EOT, respectively. CONCLUSIONS: The prognosis of decompensated cirrhotic patients receiving DAA was stratified by liver function at 12 weeks after the EOT, not by baseline liver function.

Effects of Sprayable, Highly Adhesive Hydrophobized Gelatin Microparticles on Endoscopic Submucosal Dissection: A Swine Model.

INTRODUCTION: Sprayable wound dressings containing hydrophobized microparticles (hMPs) are characterized by strong adhesiveness. We examined the effect of hMPs derived from Alaska pollock gelatin on endoscopic submucosal dissection (ESD) ulcers. METHODS: (1) In an in vivo model of miniature swine gastric ESD, gastric ulcers were created by ESD and then sprayed with hMPs or untreated followed by microscopic examination. (2) In an ex vivo ESD model of resected stomach, a pinhole-shaped perforation was created on the ESD ulcer of resected stomach; hMPs were then sprayed on the perforation; and air leakage and intragastric pressure were measured. (3) In an in vivo duodenal ESD model of miniature swine, duodenal artificial ESD ulcers with pinhole-shaped perforation were examined; ulcers were classified into hMPs-sprayed and nonsprayed groups, and inflammation in the intrinsic muscle layer and serosa were compared between the groups. RESULTS: (1) Histological observation of submucosal tissues showed a decreased number of invading inflammatory cells in hMP-sprayed tissues compared with the control in miniature swine gastric ESD (p < 0.05). In addition, the rates of anti-alpha smooth muscle actin and type I collagen positivity were significantly lower in the hMPs group than in the control group (p < 0.05). (2) Intragastric pressure could not be measured in the nonsprayed group, whereas no air leakage was observed in the sprayed group when pressurized up to 26 mm Hg in the resected stomach model. (3) The sprayed group showed suppressed inflammation of the intrinsic muscular layer and serosa in both cases compared with the nonsprayed group in miniature swine duodenal ESD (p < 0.05). CONCLUSIONS: Sprayable, tissue-adhesive hMPs are a promising medical material for intraoperative and postoperative treatment of ESD-induced wound via anti-inflammation and strong adhesiveness.

Efficacy of endoscopic ultrasonography in evaluating tumor thickness in patients with superficial pharyngeal carcinoma: A pilot study.

OBJECTIVES: A histopathological tumor thickness of ≥1000 µm has been reported as one of many risk factors for recurrent lymph node metastasis in superficial pharyngeal cancer (SPC). However, methods for assessing this risk factor preoperatively have not yet been established. Hence, the current study aimed to evaluate the efficacy of endoscopic ultrasonography (EUS) in measuring tumor thickness preoperatively in patients with SPC. METHODS: This single-center retrospective study included 44 consecutive patients with 47 lesions who underwent endoscopic submucosal dissection (ESD). Prior to surgery, EUS examination was performed while under general anesthesia. Further, microvascular irregularity in the target lesion was evaluated using the Japan Esophageal Society (JES) magnification endoscopic classification system. RESULTS: A significant correlation was noted between histopathological and EUS tumor thickness (Spearman's correlation r == 0.879, p < 0.001). In tumors ≥1000 µm thick on histopathology, the cutoff value for EUS tumor thickness was 2.6 mm, and the following values were obtained: sensitivity, 100%; specificity, 81.8%; positive predictive value (PPV), 70%; negative predictive value (NPV), 100%; and accuracy, 87.2%. In B2 lesions ≥1000-µm thick, the following values were obtained: sensitivity, 85.7%; specificity, 90.9%; PPV, 80%; NPV, 93.8%; and accuracy, 89.4%. The diagnostic accuracy rate of combined EUS and the JES magnifying endoscopic classification system was 95.7%. CONCLUSIONS: Tumor thickness assessed using EUS was effective in diagnosing histopathological tumor thickness of ≥1000 µm. The combined use of EUS and the JES magnifying endoscopic classification system may be useful for assessing preoperative risk factors for lymph node metastasis in SPC.

Acetaldehyde breath test as a cancer risk marker in patients with esophageal and hypopharyngeal squamous cell carcinoma.

Patients with inactive acetaldehyde dehydrogenase 2 (ALDH2) are at high risk for esophageal squamous cell carcinoma (ESCC) and hypopharyngeal squamous cell carcinoma (HPSCC). The acetaldehyde breath test (ABT) may demonstrate ALDH2 gene polymorphisms. We evaluated the usefulness of the ABT in patients with ESCC and HPSCC. The squamous cell carcinoma (SCC) group consisted of 100 patients who were treated with endoscopic submucosal dissection (ESD) for ESCC or HPSCC, and the control group (HC) consisted of 275 healthy subjects. The SCC group comprised the "single subgroup" (n = 63), in which a single lesion was initially treated with ESD, and the "multiple subgroup" (n = 31), in which multiple lesions were initially treated with ESD. First, we compared the groups' risk factors for carcinogenesis and measured the acetaldehyde-to-ethanol (A/E) ratio. Then we tested the groups' differences in the abovementioned carcinogenic risk factors. We found that the proportion of individuals in the SCC group with inactive ALDH2 (A/E ratio ≥ 23.3) was significantly higher than that in the HC group (p = 0.035), as was the A/E ratio (p < 0.001). Also, the proportion of individuals with inactive ALDH2 in the multiple subgroup was significantly higher than that in single subgroup (p = 0.015), as was the A/E ratio (p = 0.008). In conclusion, ABT may be a potential screening tool for detecting people at risk of ESCC and HPSCC. In addition, it could be a useful tool in detecting patients at risk of multiple or double carcinomas among patients with ESCC and HPSCC. Trial registration: Trial Registration number: UMIN000040615 [https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000040615], Data of Registration: 01 46 June 2020, retrospectively registered.

Robust closure of post-endoscopic submucosal dissection perforation by microparticle-based wound dressing.

Endoscopic submucosal dissection (ESD) has been used as a minimally invasive cancer treatment for early-stage gastrointestinal cancer. However, cancer dissection in thin tissues, such as the duodenum and large intestine, often cause post-ESD and delayed perforation, which elicit severe complications. In this study, we report a microparticle-based wound dressing with hydrophobically-modified gelatin that can close the perforation after ESD. Hydrophobized microparticles were prepared using a coacervation method in a water/ethanol mixed solvent. The optimized alkyl chain length and degree of substitution of hydrophobic groups improved the mechanical strength of the hydrogel formed by hydration and fusion of the microparticles. The hydrogels formed on tissue defects revealed higher burst strength in ex vitro perforation models using duodenum, large intestine, and stomach under wet conditions compared with hydrogels without hydrophobic modification. The particle fusion was determined to be a crucial step to yield a high burst strength. An in vivo degradability evaluation showed that microparticle hydrogels subcutaneously implanted in rats degraded within 14 days. The microparticle wound dressing is expected to be applicable to post-ESD perforation and prevent delayed perforation.

Covering Post-Endoscopic Submucosal Dissection Ulcers in Miniature Swine with Hexanoyl (Hx:C6) Group-Modified Alkaline-Treated Gelatin Porous Film (HAG) Induces Proper Healing by Decreasing Inflammation and Fibrosis.

BACKGROUND AND AIMS: Hexanoyl (Hx:C6) group-modified alkaline-treated gelatin porous film (HAG) is a newly developed degradable hydrogel characterized by strong adhesiveness and high affinity for vascular endothelial growth factor (VEGF). The aim of this study was to clarify the effect of HAG sheets on the healing process of post-endoscopic submucosal dissection (ESD) porcine gastric artificial ulcers. METHODS: (1) To evaluate the adhesiveness of HAG sheets over time, we performed ESD to create 1 artificial ulcer and covered the lesion with 1 HAG sheet using 1 miniature swine. We observed 2 ulcers by endoscopic and microscopic examinations. (2) To examine the effect of HAG sheets on post-ESD ulcer healing, we performed ESD using 5 miniature swine. The artificial ulcers were covered with HAG sheets, or left uncovered after ESD (day 0), followed by macroscopic and microscopic examinations. On days 7 and 14, we observed 2 ulcers by endoscopic examinations. On day 14, the animals were sacrificed, and histological examination was performed on the 3 stomachs that could be extirpated. RESULTS: (1) On day 7, adhesion of HAG sheets was observed. (2) Gastric ulcer area on day 7 was significantly larger in the covered ulcers than in the non-covered ulcers (p = 0.046). On day 14, although there was no significant difference in ulcer area irrespective of covering (p = 0.357), the covered ulcers tended to repair less fold convergence than non-covered ulcers. The covered ulcer sheets significantly decreased inflammatory cell infiltration (p = 0.011), but significantly increased the abundance of macrophages (p = 0.033), in submucosal layers. Also, the abundance of alpha-smooth muscle actin-positive cells in submucosal layers of the covered ulcers was significantly reduced (p = 0.044), leading to a decrease in collagen accumulation. In addition, fibrosis and atrophy of the muscularis propria were significantly lower for covered ulcers than for non-covered ulcers. Furthermore, microvessels and VEGF-positive cells were significantly more abundant in the submucosal layers of the covered ulcers (p < 0.001 and p = 0.024, respectively). CONCLUSIONS: HAG sheets induced post-ESD ulcer healing with less submucosal inflammation and muscularis propria injury and have the potential to decrease excess scarring.

Multifunctional Hydrophobized Microparticles for Accelerated Wound Healing after Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection (ESD) provides strong therapeutic benefits for early gastrointestinal cancer as a minimally invasive treatment. However, there is currently no reliable treatment to prevent scar contracture resulting from ESD which may lead to cicatricial stricture. Herein, a multifunctional colloidal wound dressing to promote tissue regeneration after ESD is demonstrated. This sprayable wound dressing, composed of hydrophobized microparticles, exhibits the multifunctionality necessary for wound healing including tissue adhesiveness, blood coagulation, re-epithelialization, angiogenesis, and controlled inflammation based on hydrophobic interaction with biological systems. An in vivo feasibility study using swine gastric ESD models reveals that this colloidal wound dressing suppresses fibrosis and accelerates wound healing. Multifunctional colloidal and sprayable wound dressings have an enormous therapeutic potential for use in a wide range of biomedical applications including accelerated wound healing after ESD, prevention of perforation, and the treatment of inflammatory diseases.

[A case of postoperative recurrent gastric cancer resembling esophageal achalasia diagnosed by staging laparoscopy].

A 65-year-old man underwent subtotal gastrectomy for advanced gastric cancer. The histological type of the cancer was signet-ring cell carcinoma, and the clinical stage was stage IB (T2N0M0). Three years after surgery, the patient had the following symptoms:dysphagia, odynophagia, and weight loss. Esophageal endoscopy and esophagography revealed a circular stenosis covered with the normal mucosa between the middle esophagus and the esophagogastric junction. Histologically, the samples obtained by staging laparoscopy revealed signet-ring cell carcinoma. Tucker's criteria are an important tool for differentiating secondary achalasia from primary achalasia with clinical value. Therefore, we suggest that staging laparoscopy is useful for the histological diagnosis of recurrent gastric cancer.