Clinical outcomes and risk factors for perforation in gastric endoscopic submucosal dissection: A prospective pilot study

AIM: To evaluate clinical outcomes and risk factors for endoscopic perforation during endoscopic submucosal dissection (ESD) in a prospective study. METHODS: We investigated the clinical outcomes and risk factors for the development of perforation in 98 consecutive gastric neoplasms undergoing ESD regarding. Demographic and clinical parameters including patient-, tumor-, and treatment-related factors, clinical parameters, and duration of hospital stay were analyzed for risk factors for perforation. In subgroup analysis, we also compared the clinical outcomes between perforation and "silent" free air without endoscopically visible perforation detected only by computed tomography.RESULTS: Perforation was identified in 8.2% of patients. All patients were managed conservatively by the administration of antibiotics. The mean procedure time was significantly longer in patients with endoscopic perforation than in those without. According to the receiver-operating characteristic analysis, the resulting cutoff value of the procedure time for perforation was 115 min (87.5% sensitivity, 56.7% specificity). Prolonged procedure time (≥ 115 min) was associated with an increased risk of perforation (odds ratio 9.15; 95%CI: 1.08-77.54; P = 0.04). Following ESD, body temperature and C-reactive protein level were significantly higher in patients with perforation than in those without (P = 0.02), whereas there was no difference between these patient groups on the starting day of oral intake or of hospitalization. In subgroup analysis, the post-ESD clinical course was not different between endoscopic perforation and silent free air. CONCLUSION: Only prolonged procedure time (≥ 115 min) was significantly associated with perforation. The clinical outcomes of perforation are favorable and are comparable to those of patients with or without silent free air.

What types of early gastric cancer are indicated for endoscopic ultrasonography staging of invasion depth?

AIM To clarify the diagnostic efficacy and limitations of endoscopic ultrasonography(EUS) and the characteristics of early gastric cancers(EGCs) that are indications for EUS-based assessment of cancer invasion depth.METHODS We retrospectively investigated the cases of 153 EGC patients who underwent conventional endoscopy(CE) and EUS(20 MHz) before treatment.RESULTS We found that 13.7% were "inconclusive" cases with low-quality EUS images, including all nine of the cases with protruded(0-I)-type EGCs. There was no significant difference in the diagnostic accuracybetween CE and EUS. Two significant independent risk factors for misdiagnosis by EUS were identified-ulcer scarring [UL(+); odds ratio(OR) = 4.49, P = 0.003] and non-indication criteria for endoscopic resection(ER)(OR = 3.02, P = 0.03). In the subgroup analysis, 23.1% of the differentiated-type cancers exhibiting SM massive invasion(SM2) invasion(submucosal invasion ≥ 500 μm) by CE were correctly diagnosed by EUS, and 23.1% of the undifferentiated-type EGCs meeting the expanded-indication criteria for ER were correctly diagnosed by EUS.CONCLUSION There is no need to perform EUS for UL(+) EGCs or 0-I-type EGCs, but EUS may enhance the pretreatment staging of differentiated-type EGCs with SM2 invasion without UL or undifferentiated-type EGCs revealed by CE as meeting the expanded-indication criteria for ER.

Histological diagnosis of gastric submucosal tumors: A pilot study of endoscopic ultrasonography-guided fine-needle aspiration biopsy vs mucosal cutting biopsy

AIM: To compare the usefulness of endoscopic ultrasonography-guided fine-needle aspiration biopsy(EUS-FNAB) without cytology and mucosal cutting biopsy(MCB) in the histological diagnosis of gastric submucosal tumor(SMT).METHODS: We prospectively compared the diagnostic yield, feasibility, and safety of EUS-FNAB and those of MCB based on endoscopic submucosal dissection. The cases of 20 consecutive patients with gastric SMT ≥1 cm in diameter. who underwent both EUS-FNAB and MCB were investigated.RESULTS: The histological diagnoses were gastrointestinal stromal tumors(n = 7), leiomyoma(n =6), schwannoma(n = 2), aberrant pancreas(n = 2), and one case each of glomus tumor, metastatic hepatocellular carcinoma, and no-diagnosis. The tumors' mean size was 23.6 mm. Histological diagnosis was made in 65.0% of the EUS-FNABs and 60.0% of the MCBs, a nonsignificant difference. There were no significant differences in the diagnostic yield concerning the tumor location or tumor size between the two methods. However, diagnostic specimens were significantly more frequently obtained in lesions with intraluminal growth than in those with extraluminal growth by the MCB method(P = 0.01). All four SMTs with extraluminal growth were diagnosed only by EUSFNAB(P = 0.03). No complications were found in either method.CONCLUSION: MCB may be chosen as an alternative diagnostic modality in tumors showing the intraluminal growth pattern regardless of tumor size, whereas EUSFNAB should be performed for SMTs with extraluminal growth.

Diagnosis of small intramucosal signet ring cell carcinoma of the stomach by non-magnifying narrow-band imaging: A pilot study

AIM: To examine the efficacy of non-magnifying narrow-band imaging(NM-NBI) imaging for small signet ring cell carcinoma(SRC).METHODS: We retrospectively analyzed 14 consecutive small intramucosal SRCs that had been treated with endoscopic submucosal dissection(ESD) and 14 randomly selected whitish gastric ulcer scars(control). The strength and shape of the SRCs and whitish scars by NM-NBI and white-light imaging(WLI) were assessed with Image J(NIH, Bethesda).RESULTS: NM-NBI findings of SRC showed a clearly isolated whitish area amid the brown color of the surrounding normal mucosa. The NBI index, which indicates the potency of NBI for visualizing SRC, was significantly higher than the WLI index(P = 0.001), indicating SRC was more clearly identified by NM-NBI. Although the NBI index was not significantly different between SRCs and controls, the circle(C)-index, as an index of circularity of tumor shape, was significantly higher in SRCs(P = 0.001). According to the receiveroperating characteristic analysis, the resulting cut-off value of the circularity index(C-index) for SRC was 0.60(85.7% sensitivity, 85.7% specificity). Thus a lesion with a C-index ≥ 0.6 was significantly more likely to be an SRC than a gastric ulcer scar(OR = 36.0; 95%CI: 4.33-299.09; P = 0.0009).CONCLUSION: Small isolated whitish round area by NM-NBI endoscopy is a useful finding of SRCs which is the indication for ESD.

SRT1720, a SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice

Diagnosis and management of interstitial lung diseases (ILDs), caused by lung epithelial injury followed by apoptosis, are often challenging. It has been controversial whether the SIRT1 protein, a principal modulator of longevity due to caloric restriction, ameliorates or aggravates ILD in animal models. Here we examined the effect of SRT1720, a syn- thetic activator of SIRT1, on bleomycin-induced lung injury in a mouse model and apoptosis in cultured epithelial cells. Oral intubation of SRT1720 over a period of 15 days caused body weight loss and a high mortality rate among bleomy- cin-treated mice. Histological examinations showed that the SRT1720 load increased fibrosis in the bleomycin-treated lung. An analysis of bronchoalveolar lavage fluid revealed remarkably increased numbers of inflammatory cells in the SRT1720-treated group. Moreover, the apoptosis of A549 lung cancer cells, caused by X-ray irradiation and an anti-Fas activating antibody, was promoted by SRT1720. These results indicate that SRT1720 not only aggravates bleomy- cin-induced ILD, but stimulates the apoptosis of physically and biologically stimulated A549 cells. While SIRT1 acti- vators are considered promising for the treatment of conditions such as diabetes mellitus, fatty liver, and chronic ob- structive pulmonary diseases, an excess of food containing SIRT1 activators may be harmful depending on the disease state, especially in the case of acute inflammation.

Predictive Factors Differ between Hepatocellular Carcinoma Occurrence and Recurrence after Sustained Virological Responses by Direct-Acting Antivirals in Patients with Hepatitis C

Background: Interferon-free direct-acting antivirals (DAA) have markedly increased the sustained virological response (SVR) rate among patients with hepatitis C. Although DAA inhibit the development of hepatocellular carcinoma (HCC), predictive factors remain unclear. The aims of the present study were to investigate predictive factors for HCC occurrence and recurrence after SVR by DAA in prospectively followed patients with hepatitis C (HCV). Methods: One hundred and eighty-three HCV-infected patients treated with DAA and achieving SVR were prospectively followed up for more than one year. Among these patients, 166 had no history of HCC before DAA therapy, while 17 had a history of being treated for HCC by radiofrequency ablation or resection before the initiation of DAA. Liver stiffness (LS) measurements were conducted using transient elastography, and LS was assessed at the initiation of DAA (LS0), 24 weeks after the initiation of DAA (LS24), 48 weeks after (LS48), and every year after that. Results: HCC occurred in 7 out of 166 patients without a history of HCC (4.2%), and recurred in 9 out of 17 with a history of HCC (52.9%). Patients with a history of HCC were significantly older, mainly males, had higher alpha-fetoprotein (AFP) levels before DAA and at SVR24, higher Fib-4 levels, and higher LS0, 24, and 48 than those without a history of HCC. Age (p = 0.013) and AFP at SVR24 (p = 0.036) correlated with occurrence. LS48 (p = 0.043) correlated with recurrence. Conclusions: Predictive factors differed between HCC occurrence and recurrence after SVR by DAA in HCV patients. High recurrence rates were due to fibrosis in the liver being more advanced in patients with than in those without a history of HCC. Age and AFP at SVR24 were identified as predictive factors of HCC occurrence and LS48 of HCC recurrence.

The Evaluation of Tolvaptan Therapy and Long-Term Prognosis in Hepatocellular Carcinoma with Refractory Ascites

We investigated Tolvaptan efficacy and long-term prognosis with focus on nutrition in 20 patients with refractory hepatic ascites in hepatocellular carcinoma (HCC). Bloating improved in 55% of patients, as determined using a Japanese version of the Support Team Assessment Schedule. Nutritional status improved with Tolvaptan treatment, based on the Controlling Nutritional Status score and Onodera’s prognostic nutritional index. Long-term prognosis was better in responders than in non-responders (mean survival time: 308 days vs. 97 days, p = 0.031). Tolvaptan was even effective in many patients with HCC, with additional improvement in long-term prognosis expected with improvement in the nutritional status.

The Effect of Loop Diuretics on Sarcopenia and Long-Term Prognosis in Patients with Refractory Hepatic Ascites Treated with Tolvaptan

We investigated sarcopenia, focusing on the dose of loop diuretics used in 70 patients with refractory hepatic ascites treated with tolvaptan. Bloating improved in 68.5% of patients, as determined using the Japanese version of the Support Team Assessment Schedule. The psoas muscle index (PMI) was used to define sarcopenia. A statistically significant difference was observed in the PMI between patients receiving low-dose (3.6 ± 1.2 cm2/m2) and high-dose furosemide (3.1 ± 1.2 cm2/m2) before tolvaptan treatment (P = 0.048). The PMI increased from 3.2 ± 1.1 cm2/m2 to 3.5 ± 1.3 cm2/m2 (P = 0.002) in responders, but decreased from 3.4 ± 1.2 cm2/m2 to 3.0 ± 1.0 cm2/m2 (P = 0.106) in non-responders before and after tolvaptan treatment, respectively. The long-term prognosis improved in responders compared with non-responders (mean survival time: 646 days vs. 228 days, P < 0.001). Early introduction of tolvaptan treatment is necessary to prevent the progression of sarcopenia.