Efficacy and Safety of TJP-008 Compared to 2 L PEG with Ascorbate in Colon Cleansing: A Randomized Phase 3 Trial.

BACKGROUND/AIMS: Polyethylene glycol (PEG)-based bowel preparations are effective cleansing agents for colonoscopy. However, they require relatively large volumes to be used even with agents such as 2 L PEG with ascorbate (2LPEG). This phase 3, randomized, single-blinded, multicenter, parallel-group study compared the efficacy of 1 L PEG with high-dose ascorbate, TJP-008, to 2LPEG. METHODS: Patients undergoing colonoscopy were randomized (1:1:1) to receive TJP-008 as 1-day split dose (TJP-008-1) or 2-day split dose (TJP-008-2) regimen or to receive 2LPEG as a 2-day split dose regimen. Cleansing efficacy was evaluated using the Harefield Cleansing Scale. The primary endpoint was overall bowel cleansing success. Full analysis set (FAS) and per protocol set (PPS) analyses were performed. RESULTS: Of the 314 screened patients, efficacy was assessed in the following patient numbers (FAS/PPS): total (293/285), TJP-008-1 (98/94), TJP-008-2 (97/95), and 2LPEG (98/96). FAS revealed noninferiority between TJP-008 and 2LPEG with regard to overall success (TJP-008-2, 99.0%; TJP-008-1, 95.9%; 2LPEG, 94.9%; p=0.100 and p=0.733, respectively). PPS also showed noninferiority (p=0.721 and p=0.211, respectively). However, the PPS analyses showed a higher bowel cleansing score for TJP-008-2 for high-quality cleansing in the right colon (TJP-008-2 83.2% vs 2LPEG 62.5%; p=0.005). CONCLUSIONS: TJP-008 is a new low-volume cleansing agent with a colon cleansing efficacy comparable to that of standard 2LPEG that exhibits significant safety and tolerability.

Increased heat shock protein 70 expression attenuates pancreatic fibrosis induced by dibutyltin dichloride.

OBJECTIVES: Heat shock protein (HSP) 70 performs a chaperoning function and protects cells against injury. Although the effect of HSPs against acute inflammatory change has been proven, the relationship between HSP70 and chronic pancreatitis remains unclear. This study aimed to investigate the protective effect of increased HSP70 expression induced by thermal stress against pancreatic fibrosis in experimental chronic pancreatitis. MATERIALS AND METHODS: Two experiments to evaluate pancreatic HSP70 expression induced by thermal stress and determine the effect of increased HSP70 expression against pancreatic fibrosis were performed. To investigate HSP70 expression, rats were immersed in a warm bath and sequentially killed, and pancreatic HSP70 expression was measured. To study the effect of increased HSP70 expression, pancreatic fibrosis was induced by intravenous injection of dibutyltin dichloride (DBTC) and analyzed under repeated thermal stress. The severity of pancreatic fibrosis was measured. RESULTS: Thermal stress significantly increased HSP70 expression in the pancreas. HSP70 expression peaked at 6-12 h after warm bathing, and the increased HSP70 expression was associated with the attenuation of pancreatic fibrosis. Although pancreatic fibrosis was induced by DBTC injection, HSP70 expression induced by repeated thermal stress diminished the severity of atrophy and fibrosis. On western blot analysis, collagen type 1 expression was diminished in the increased HSP70 expression group, but not α-smooth muscle actin expression. CONCLUSIONS: Thermal stress could increase pancreatic HSP70 expression, and induced HSP70 expression showed a protective effect against pancreatic fibrosis. Modulation of HSP70 expression could be a potential therapeutic target in the treatment of chronic pancreatitis.

Selenium Administration Attenuates 5-Flurouracil-Induced Intestinal Mucositis.

Chemotherapy-induced mucositis is mediated by the release of proinflammatory cytokines and reactive oxygen species. Selenium has several metabolic functions, including the protection of membrane lipids and macromolecules against oxidative damage. However, to date, there is little evidence on the effect of trace elements on intestinal mucositis after chemotherapy. This study investigated the protective effect of selenium against chemotherapy-induced mucositis in rats. Twenty-four 9-wk-old female Wistar rats were randomized to 4 groups: control, selenium, 5-fluorouracil (5-FU), and 5-FU plus selenium. Mucositis was induced by a single dose of 5-FU (400 mg/kg BW) via intraperitoneal injection, and selenium was administered by a single intraperitoneal dose of sodium selenite (0.2 mg/kg BW). Diarrhea and weight loss after 5-FU administration were attenuated by selenium treatment. The mean villus height in the 5-FU plus selenium group was significantly taller than rats administered with 5-FU alone, but not significantly different compared to the control group. Interleukin (IL)-1ß and tumor necrosis factor (TNF)-α mRNA expression were significantly lower in the 5-FU plus selenium group than in the 5-FU only group (IL-1ß, P < 0.01; TNF-α, P < 0.05). These findings indicate that selenium protects the mucosa during chemotherapy via its anti-inflammatory effects and its suppression of cytotoxic cytokine production.

Polyethylene glycol plus ascorbic acid for bowel preparation in chronic kidney disease.

The safety of polyethylene glycol plus ascorbic acid has not been fully investigated in patients with renal insufficiency. High-dose ascorbic acid could induce hyperoxaluria, thereby causing tubule-interstitial nephritis and renal failure. This study aims to evaluate the safety and efficacy of polyethylene glycol plus ascorbic acid in patients with chronic kidney disease.We retrospectively reviewed prospectively collected data on colonoscopy in patients with impaired renal function. Patients were divided into 2 groups: 2 L polyethylene glycol plus ascorbic acid (n = 61) and 4 L polyethylene glycol (n = 80). The safety of the 2 groups was compared by assessing the differences in laboratory findings before and after bowel cleansing.The laboratory findings were not significantly different before and after the administration of 2 L polyethylene glycol plus ascorbic acid or 4 L polyethylene glycol. In both groups, the estimated glomerular filtration rate was not influenced by the administration of the bowel-cleansing agent. Patients' reports on tolerance and acceptability were better in the 2 L polyethylene glycol plus ascorbic acid group than in the 4 L polyethylene glycol group.The 2 L polyethylene glycol plus ascorbic acid solution is a safe choice for bowel preparation before colonoscopy in patients with impaired renal function.

Coffee enema for preparation for small bowel video capsule endoscopy: a pilot study.

Coffee enemas are believed to cause dilatation of bile ducts and excretion of bile through the colon wall. Proponents of coffee enemas claim that the cafestol palmitate in coffee enhances the activity of glutathione S-transferase, an enzyme that stimulates bile excretion. During video capsule endoscopy (VCE), excreted bile is one of the causes of poor preparation of the small bowel. This study aimed to evaluate the feasibility and effect of coffee enema for preparation of the small bowel during VCE. In this pilot study, 17 of 34 patients were assigned to the coffee enema plus polyethylene glycol (PEG) 2 L ingestion group, whereas the 17 remaining control patients received 2 L of PEG only. The quality of bowel preparation was evaluated in the two patient groups. Bowel preparations in the proximal segments of small bowel were not differ between two groups. In the mid and distal segments of the small intestine, bowel preparations tend to be better in patients who received coffee enemas plus PEG than in patients who received PEG only. The coffee enema group did not experience any complications or side effects. Coffee enemas may be a feasible option, and there were no clinically significant adverse events related to coffee enemas. More prospective randomized studies are warranted to improve small bowel preparation for VCE.

Usefulness of warm water and oil assistance in colonoscopy by trainees.

BACKGROUND AND STUDY AIMS: Success rate of cecal intubation, endoscopist's difficulty, and procedure-related patient pain are still problems for beginners performing colonoscopy. New methods to aid colonoscopic insertion such as warm water instillation and oil lubrication have been proposed. The aim of this study is to evaluate the feasibility of using warm water or oil in colonoscopy. METHODS: Colonoscopy was performed in 117 unsedated patients by three endoscopists-in-training. Patients were randomly allocated to three groups, using a conventional method with administration of antispasmodics, warm water instillation, and oil lubrication, respectively. Success rate of total intubation within time limit (15 min), cecal intubation time, degree of endoscopist's difficulty, and level of patient discomfort were compared among the three groups. RESULTS: Cecal intubation time was shorter in the warm water group than in the conventional and oil groups. Degree of procedural difficulty was lower in the warm water group, and patient pain score was higher in the oil lubrication group, compared with the other groups. However, there was no significant difference in success rate of intubation within time limit among the three groups. CONCLUSIONS: The warm water method is a simple, safe, and feasible method for beginners. Oil lubrication may not be a useful method compared with conventional and warm water method.