Role of probe-based confocal laser endomicroscopy-targeted biopsy in the molecular and histopathological study of gastric cancer.

BACKGROUND AND AIM: A high yield of biopsy is mandatory to perform molecular genetic research with endoscopically obtained gastric cancer tissues. We evaluated whether probe-based confocal laser endomicroscopy (pCLE) can increase the yield of endoscopic biopsy for gastric cancer compared with white light endoscopy (WLE). METHODS: All lesions in the pCLE and WLE groups were initially evaluated through WLE. In the pCLE group, lesions were further examined through pCLE. In the pilot study, five and three biopsy specimens were obtained for histopathological examination and tumor marker analysis, respectively. In the confirmatory study, six biopsy specimens for histopathological evaluation were obtained. RESULTS: A total of 30 gastric cancers and 61 undifferentiated-type gastric cancers were analyzed in the pilot and confirmatory studies, respectively. The proportion of cancer cells in biopsy samples of poorly differentiated adenocarcinoma or signet ring cell carcinoma was higher in the pCLE group than in the WLE group in both the pilot and confirmatory studies (pilot: median proportion, 65% vs 30%, P = 0.010; confirmatory: mean ± standard deviation, 49.5 ± 29.3 vs 29.3 ± 13.7, P = 0.002). The expression ratio of tumor markers including carcinoembryonic antigen, GW112, HOX transcript antisense RNA, and H19 tended to be higher in the pCLE group than in the WLE group. CONCLUSION: Probe-based confocal laser endomicroscopy-targeted biopsy provided superior results in terms of the proportion of cancer cells in biopsy samples compared with WLE-targeted biopsy in gastric cancer with undifferentiated histology.

Effectiveness of the polysaccharide hemostatic powder in non-variceal upper gastrointestinal bleeding: Using propensity score matching.

BACKGROUND AND AIM: Recently, the application of hemostatic powder to the bleeding site has been used to treat active upper gastrointestinal bleeding (UGIB). We aimed to assess the effectiveness of the polysaccharide hemostatic powder (PHP) in patients with non-variceal UGIB. METHODS: We reviewed prospectively collected 40 patients with UGIB treated with PHP therapy between April 2016 and January 2017 (PHP group) and 303 patients with UGIB treated with conventional therapy between April 2012 and October 2014 (conventional therapy group). We compared the rate of successful hemostasis and the rebleeding between the two groups after as well as before propensity score matching using the Glasgow-Blatchford score and Forrest classification. RESULTS: Thirty patients treated with the PHP and 60 patients treated with conventional therapy were included in the matched groups. Baseline patient characteristics including comorbidities, vital signs, and bleeding scores were similar in the matched groups. The rate of immediate hemostasis and 7-day and 30-day rebleeding were also similar in the two groups before and after matching. In the subgroup analysis, no significant differences in immediate hemostasis or rebleeding rate were noted between PHP in monotherapy and PHP combined with a conventional hemostatic method. At 30 days after the therapy, there were no significant PHP-related complications or mortality. CONCLUSIONS: Given its safety, the PHP proved feasible for endoscopic treatment of UGIB, having similar effectiveness as that of conventional therapy. The PHP may become a promising hemostatic method for non-variceal UGIB.

Efficacy of hemostatic powder in preventing bleeding after gastric endoscopic submucosal dissection in high-risk patients.

BACKGROUND AND AIM: The prevention of post-endoscopic submucosal dissection (ESD) bleeding in high-risk patients is an important problem. This study evaluated the efficacy of polysaccharide hemostatic powder in preventing post-ESD bleeding in high-risk patients. METHODS: Patients at high risk for post-ESD bleeding were prospectively enrolled between December 2015 and July 2016. A high risk of post-ESD bleeding was considered if the patients were taking antithrombotic agents or had undergone a large resection (specimen size ≥ 40 mm). The endpoints were Forrest classification of the post-ESD ulcer on second-look endoscopy 2 days after the procedure and bleeding rates within 48 h and at 4 weeks. RESULTS: Forty-four patients underwent gastric ESD and treatment with hemostatic powder. Among them, 33 patients (70.5%) underwent large resection (≥ 40 mm) without antithrombotic therapy, and 13 patients (29.5%) received antithrombotic therapy. The mean resected specimen size was 55.3 ± 13.9 mm. The proportion of high-risk delayed bleeding lesions (Forrest IIa) at second-look endoscopy was 4.5% (2/44). The overall bleeding rate was 9.1% (4/44). There was no early bleeding event. The median (interquartile range) timing of bleeding after the procedure was 12.5 (interquartile range 10.3-15.5) days. The bleeding rate in the large resection (≥ 40 mm) group without antithrombotic therapy and the antithrombotic therapy group was 3.2% (1/33) and 23.1% (3/13), respectively. CONCLUSIONS: Hemostatic powder may be a promising new simple and effective method to prevent early post-ESD bleeding in high-risk patients, especially for those with larger resection. (Clinical trial registration number: NCT02625792).

Long-term outcomes after noncurative endoscopic resection of early gastric cancer: the optimal time for additional endoscopic treatment.

BACKGROUND AND AIMS: We aimed to evaluate long-term outcomes with noncurative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and surveillance strategies such as the optimal time for additional endoscopic treatment in patients with noncurative ESD. METHODS: Of 2527 patients who underwent gastric ESD for EGC, 512 (20.3%) patients with noncurative resection were reviewed. Noncurative resection is defined as positive resected margins on histology, lymphovascular infiltration, or beyond the expanded criteria for ESD. RESULTS: The mean ± standard deviation follow-up duration was 79.0 ± 55.7 months. A total of 264 patients (51.6%) and 50 patients (9.8%) underwent surgery and endoscopic treatment after noncurative resection, respectively, whereas 198 patients (38.7%) were observed. Cancer-specific survival and disease-free survival rates were significantly different among the surgery, other endoscopic treatment, and observation groups (96.7%, 86.8%, and 86.2%, respectively; P =.030; and 92.5%, 73.6%, and 63.0%, respectively; P < .001). When patients who underwent surgery were excluded, the disease-free survival rate of recurrence was not significantly different between the endoscopic treatment and observation groups (73.6% vs 63.0%; P = .548). To exclude the potential for the presence of lymph node metastasis, we further analyzed disease-free survival of local recurrence by comparing the patients with only a positive lateral resection margin. The disease-free survival rate was higher in the endoscopic treatment group than in the observation group (89.2% vs 69.1%; P = .023). Moreover, additional endoscopic treatment within 3 months showed significant associations with lower risk of local recurrence on multivariate analysis (hazard ratio, 0.017; 95% confidence interval, 0.002-0.260; P = .003). CONCLUSIONS: In patients with noncurative ESD, additional surgery showed a better long-term outcome; moreover, when a positive lateral resection margin was the only noncurative factor, additional endoscopic treatment within 3 months could be considered to improve disease-free survival.

Long-term outcomes of endoscopic submucosal dissection in comparison to surgery in undifferentiated-type intramucosal gastric cancer using propensity score analysis.

BACKGROUND: The treatment of intramucosal early gastric cancer with undifferentiated-type histologies (UD-EGCs) using endoscopic submucosal dissection (ESD) is controversial. This study aimed to compare the clinical and oncologic long-term outcomes of ESD and surgery for UD-EGCs. METHODS: A prospectively collected database of patients who underwent ESD or surgery between January 2006 and December 2012 was established. Patients who diagnosed with UD-EGC and satisfied the expanded indications of ESD were included. Clinical data from 111 patients treated with ESD and 382 patients underwent surgery were analyzed, and 1-1 propensity score-matched 81 pairs of patients were also compared. RESULTS: In both groups, two-thirds of the UD-EGCs had signet ring cell (SRC)-type histology and about 90% of UD-EGCs were flat or depressed types. The mean size of tumors was smaller in ESD group (9.7 vs. 13.2 mm; P < 0.001). After propensity score-matched, case-matching covariates were not significantly different between the groups. Disease-free survival (DFS) was significantly shorter in the ESD group, but overall survival (OS) was not different between the two groups both in overall comparison (DFS; P < 0.001 and OS; P = 0.078) and propensity score-matched analysis (DFS; P < 0.001 and OS; P = 0.850). According to histologic type, OS of SRC histology was not different between the group, both in overall comparison and propensity score-matched analysis (P = 0.286 and P = 0.210). On the other hands, OS of poorly differentiated adenocarcinoma was significantly shorter in ESD group in overall comparison (P = 0.007), but was not as so in propensity score-matched analysis (P = 0.088). CONCLUSIONS: ESD might be a complementary option for the treatment of UD-EGCs, especially in those with SRC-type histology based on strict expanded indications. Nonetheless, close endoscopic surveillance is required because of a high incidence of intragastric recurrence.

Comparative study between endoscopic submucosal dissection and surgery in patients with early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is accepted as a standard treatment in patients with early gastric cancer (EGC) who have a negligible risk of lymph node metastasis. The aim of this study was to compare the short-term and long-term outcomes between ESD and surgery in patients with EGC that fulfilled the expanded indication of ESD on their final pathologic report. METHODS: We reviewed the clinical data of patients who underwent gastric ESD and surgery between January 2007 and December 2012. Patients with pathologically confirmed EGC that fulfilled the expanded indication of ESD on their final pathologic report were analyzed. RESULTS: Among 2023 patients, 817 (40.4%) underwent ESD and 1206 (59.6%) underwent surgery. The proportion of cases meeting the absolute indication was significantly higher in the ESD group than in the surgery group (66.0 vs. 26.2%). Lesions on the middle third, >3 cm in size, flat or depressed, and of undifferentiated histology were significantly more common in the surgery group than in the ESD group. The ESD group showed lower acute complication rates [8.1% (66 of 817) vs. 18.1% (218 of 1206), P ≤ 0.001] and procedure-related mortality [0 vs. 0.3% (4 of 1206), P = 0.153] than the surgical group. The annual incidence of recurrent gastric cancer was 2.18% in the ESD group and 0.19% in the surgery group. The 5-year overall and disease-specific survival rates were not significantly different between the ESD group and the surgery group (overall survival: 96.4 vs. 97.2%, P = 0.423; disease-specific survival: 99.6 vs. 99.2%, P = 0.203). CONCLUSIONS: Although EGC lesions had poorer features in the surgery group than in the ESD group, ESD was comparable to surgery for EGCs that fulfilled the expanded indication of ESD, with lower rates of acute complication and comparable overall survival.

Prediction model for non-curative resection of endoscopic submucosal dissection in patients with early gastric cancer.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is a useful method for complete resection of early gastric cancer (EGC). However, there are still some patients who undergo additional gastrectomy after ESD because of non-curative resection. There is no model that can accurately predict non-curative resection of ESD. We aimed to create a model for predicting non-curative resection of ESD in patients with EGC. PATIENTS AND METHODS: We reviewed the medical records, including all gross findings of EGC, of patients who underwent ESD for EGCs. We divided the patients into a non-curative resection group and a curative resection group. The clinicopathologic characteristics were compared between the groups to identify the risk factors for non-curative resection of ESD. We created a scoring system based on logistic regression modeling and bootstrap validation. RESULTS: Of 1639 patients who had undergone ESD for EGCs, 272 were identified as being treated non-curatively with ESD. A large tumor size (≥20 mm), tumor location in the upper body of the stomach, the presence of ulcer, fusion of gastric folds, the absence of mucosal nodularity, spontaneous bleeding, and undifferentiated tumor histology were associated with non-curative resection of ESD. Points of risk scores were assigned for these variables based on the ß coefficient as follows: tumor size (≥20 mm), 2 points; tumor location in the upper body of the stomach, 1 point; ulcer, 2 points; fusion of gastric folds, 2 points; absence of mucosal nodularity, 1 point; spontaneous bleeding, 1 point; and undifferentiated histology, 2 points. Our risk scoring model showed good discriminatory performance on internal validation (bootstrap-corrected area under the receiver operating characteristic curve, 0.7004; 95% confidence interval, 0.6655-0.7353). CONCLUSIONS: We developed a validated prediction model that can be used to identify patients who will undergo non-curative resection of ESD. Our prediction model can provide useful information for making decisions about the treatment of EGC before performing ESD.

Antral or Pyloric Deformity Is a Risk Factor for the Development of Postendoscopic Submucosal Dissection Pyloric Strictures.

BACKGROUND/AIMS: Surgeons must be aware of risk factors for strictures before performing endoscopic submucosal dissection (ESD), to enable early interventions to prevent severe strictures. METHODS: This study was a single-center retrospective study. We reviewed the clinical data of patients who has undergone gastric ESD from January 2007 to December 2012. RESULTS: Among the 3,819 patients who had undergone gastric ESD, 11 patients (7.2%) developed pyloric strictures and received successful endoscopic balloon dilation. Significant differences were noted between the patients without and with post-ESD strictures for pretreatment of antral or pyloric deformities (46.4% vs 81.8%), the proportion of extension to the lumen circumference (>3/4, 9.4% vs 54.5%), the longitudinal extent of mucosal defects (27.9±10.1 mm vs 51.5±10.8 mm), and post-ESD bleeding (2.9% vs 27.3%). Multivariate analysis revealed that pretreatment antral or pyloric deformities (odds ratio [OR], 30.53; 95% confidence interval [CI], 1.476 to 631.565; p=0.027), larger longitudinal extent of mucosal defects (OR, 1.20; 95% CI, 1.074 to 1.340; p=0.001), and circumferential extension of ≥3/4 (OR, 13.69; 95% CI, 1.583 to 118.387; p=0.017) were independent risk factors for post-ESD stricture. CONCLUSIONS: Antral or pyloric deformities, sub-circumferential resection over more than 75% of the circumference and greater longitudinal extent of mucosal defects are independent risk factors for post-ESD stricture.

Incidence and impact of scheduled endoscopic surveillance on recurrence after curative endoscopic resection for early gastric cancer.

BACKGROUND AND AIMS: The aim of this study was to identify the incidence of recurrent lesions after endoscopic submucosal dissection (ESD) and to determine whether scheduled endoscopic surveillance might control their development and treatment. METHODS: We reviewed the clinical data of patients who underwent gastric ESD between March 2007 and April 2014. RESULTS: A total of 1347 patients who underwent curative ESD for early gastric cancer that met the expanded indication for ESD were analyzed. Of these, recurrence at the previous ESD site occurred in 39 patients, whereas recurrence in the stomach at a site other than the ESD site occurred in 102 patients. Older age, intestinal metaplasia, flat or depressed lesions, and ESD criteria were associated with recurrence in the stomach in places other than the ESD site. The annual incidence was .84% for recurrence at the previous ESD site and 2.48% for recurrence in the stomach at other than the ESD site. In cases of local recurrence and metachronous lesions, there was a significant difference between the short- and long-surveillance interval group (≤12 months vs >12 months) in the proportions of recurrent adenocarcinoma (31.9% vs 60.9%, P = .021), additional gastrectomy (7.1% vs 46.2%, P = .033), and size (8.92 ± 4.17 mm vs 18.08 ± 10.47 mm, P = .010). CONCLUSIONS: Scheduled endoscopy surveillance is necessary for detecting recurrent lesions. In addition, scheduled endoscopy surveillance might help to detect recurrent lesions at a stage early enough for a curative resection.

A Case of von Hippel-Lindau Disease with Colorectal Adenocarcinoma, Renal Cell Carcinoma and Hemangioblastomas.

von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome associated with mutations of the VHL tumor suppressor gene located on chromosome 3p25. The loss of functional VHL protein contributes to tumorigenesis. This condition is characterized by development of benign and malignant tumors in the central nervous system (CNS) and the internal organs, including kidney, adrenal gland, and pancreas. We herein describe the case of a 74-year-old man carrying the VHL gene mutation who was affected by simultaneous colorectal adenocarcinoma, renal clear cell carcinoma, and hemangioblastomas of CNS.

[A case of successful endoscopic clipping for iatrogenic colon perforation induced by peritoneal catheter insertion].

Advanced cancer patients with refractory ascites often do not respond to conventional treatments including dietary sodium restriction, diuretics, and repeated large volume paracentesis. In these patients, continuous peritoneal drainage by an indwelling catheter may be an effective option for managing refractory ascites with a relative low complication rate. Peritoneal catheter-induced complications include hypotension, hematoma, leakage, cellulitis, peritonitis, and bowel perforation. Although bowel perforation is a very rare complication, it can become disastrous and necessitates emergency surgical treatment. Herein, we report a case of a 57-year-old male with refractory ascites due to advanced liver cancer who experienced iatrogenic colonic perforation after peritoneal drainage catheter insertion and was treated successfully with endoscopic clipping.

Long-term outcomes of chronic hepatitis B virus infection in the era of antiviral therapy in Korea.

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC), and ultimately liver-related deaths. Recently, owing to potent antiviral therapy with minimal side-effects, sustained suppression of hepatitis B virus replication can be achieved, thereby preventing such complications. We aimed to reappraise clinical courses regarding disease progression in the era of antiviral therapy. METHODS: Between 2001 and 2005, treatment-naïve Korean CHB patients without cirrhosis were enrolled and followed up for at least 5 years. During follow up, antiviral therapy was commenced according to Korean Association for the Study of the Liver guidelines, if eligible, and ultrasonography and laboratory and clinical assessment were performed regularly. Primary end-points were development of cirrhosis, hepatic decompensation, HCC, or liver-related deaths. RESULTS: Of 360 patients, 323 (89.7%) received antiviral therapy such as lamivudine (70.6%), entecavir (8.7%), or telbivudine (6.5%). During follow up, cirrhosis developed in 29 (8.1%), hepatic decompensation in 4 (1.1%), and HCC in 15 (4.2%) patients. Annual incidences of cirrhosis, hepatic decompensation, and HCC were 1.05%, 0.14%, and 0.53% per person-year, respectively. Age was an independent predictor for developing cirrhosis (hazard ratio [HR] 1.075, 95% confidence interval [CI] 1.037-1.116; P < 0.001), whereas age (HR 1.060, 95% CI 1.012-1.111; P = 0.014) and cirrhosis (HR 17.470, 95% CI 5.081-60.063; P < 0.001) were those for developing HCC. CONCLUSIONS: In the era of antiviral therapy, overall clinical courses have been much improved since introduction of lamivudine in 1999. However, patients with older age or cirrhosis are still subject to HCC development despite appropriate antiviral therapy, necessitating cautious surveillance.