Pharmacokinetic-pharmacodynamic comparison of ceftriaxone regimens in acute cholangitis.

The most important factors determining the prognosis of patients with acute cholangitis (AC) are prompt biliary drainage and appropriate choice of antibiotics. This study was performed to evaluate whether dividing the number of doses based on the PK-PD theory contributes to better clinical outcome in the management of acute cholangitis. We measured ceftriaxone levels in blood and bile in 21 cases diagnosed with moderate-to-severe AC. Eleven cases were administered 2 g of ceftriaxone once-daily (group A) and 10 cases were given 1 g of ceftriaxone twice-daily (group B). The theoretical effect of ceftriaxone was evaluated by pharmacokinetic-pharmacodynamic (PK-PD) parameters. Clinical efficacy was evaluated by body temperature, white blood cell count and serum levels of C-reactive protein. Minimum level of ceftriaxone in serum (in mg/L) in groups A and B at 24 h after the first dose was 9.1 and 9.2, whereas that in bile was 2.9 and 2.5, respectively. The minimum inhibitory concentration (MIC) of ceftriaxone for all isolated bacteria was below the minimum serum and biliary concentration of ceftriaxone 24 h after the first administration (except for Enterococcus species). The MIC for isolated bacterial strains was <16 mg/L, which is the PK-PD breakpoint for ceftriaxone at 2 g/day. Both regimens showed clinical efficacy and did not contradict the effect predicted based on PK-PD.

Gastric Cancer Screening by Combined Assay for Serum Anti-Helicobacter pylori IgG Antibody and Serum Pepsinogen Levels--The ABC Method.

BACKGROUND: Helicobacter pylori (Hp) infection and gastric atrophy are both risk factors for gastric cancer. Recently it has been found that X-ray examination for gastric cancer screening does not have much effect on the detection rate for gastric cancer in Japan. A candidate for a new mass screening for gastric cancer, the ABC method, using the combination assay of Hp and serum pepsinogen, was useful for identifying the development of gastric cancer in high-risk and low-risk populations. People with higher cancer risk are recommended to receive endoscopy. The ABC method was carried out as a gastric cancer mass-screening on the initiative of Nishitokyo Medical Association in Nishitokyo city from 2011. This paper reviewed the present status of gastric cancer screening using the ABC method, including the latest results of our ongoing screening. SUMMARY: We report results for 36,627 individuals from 2011 to 2013. Among them, 16,965 received blood examination for the ABC method. Of those, 8,083 planned to undergo endoscopic examination according to stratification of the risk for the development of gastric cancer. In fact, a total of 2,911 individuals underwent endoscopic examination. Gastric cancer was detected in 65 patients, including 52 (80%) diagnosed with early gastric cancer. The ABC method was not organized screening but opportunistic screening. X-ray examination was the organized screening that was ongoing during the same period. Detection cost for 1 gastric cancer case using the ABC method was cheaper than the conventional X-ray screening method (¥1,267,452 vs. ¥2,807,763). KEY MESSAGES: Although further large epidemiological studies are required, the ABC method might be positioned as an effective mass screening for gastric cancer.

A questionnaire-based survey on the diagnosis and management of inflammatory bowel disease in East Asian countries in 2012.

BACKGROUND AND AIM: The prevalence and incidence of inflammatory bowel disease (IBD) are lower in East Asia than in Western countries; however, marked increases have recently been reported. The clinical diagnosis and medical management of IBD in East Asia differ from those in Western countries. A questionnaire-based survey was performed to gather physicians' current opinions on IBD in different East Asian countries. METHODS: Representative International Gastrointestinal Consensus Symposium (IGICS) committee members provided a questionnaire to physicians in each East Asian country studied. The questionnaire mainly focused on the diagnosis and management of IBD. RESULTS: There were 19 respondents from Japan, 10 from South Korea, 9 from the Philippines, 6 from China and 4 from Indonesia. Colonoscopy (100%) and histopathology (63%) were commonly used for the diagnosis in ulcerative colitis (UC). Conventional small bowel enteroclysis was still the most common diagnostic tool for assessing small bowel lesions in Crohn's disease (CD) in East Asia. The percentage of physicians who investigated the reactivation of Cytomegalovirus in severe or refractory patients with UC ranged from 0% in the Philippines and Indonesia to 100% in Japan and Korea. Most physicians in Korea, the Philippines, China and Indonesia chose thiopurines or anti-TNF therapy as the second-line treatment in severe refractory UC, whereas Japanese physicians preferred to use tacrolimus or leukocyte apheresis. Physicians in the Philippines and Indonesia preferred to use oral 5-aminosalicylic acid for newly diagnosed severe ileocecal CD. In contrast, Korean physicians chose oral steroids and most physicians in China and Japan preferred to use anti-TNF. Nutritional therapy to induce or maintain remission in patients with CD was commonly used in Indonesia, Japan and China. Targeted biopsies by conventional colonoscopy were the most preferred strategy for cancer surveillance in long-standing UC over random biopsies in this region. CONCLUSIONS: The present survey found that current diagnostic approaches and clinical management of IBD vary within East Asian countries.

The usefulness and safety of carbon dioxide insufflation during endoscopic retrograde cholangiopancreatography in elderly patients: a prospective, double-blind, randomized, controlled trial.

BACKGROUND/AIMS: Carbon dioxide (CO2) insufflation has been used in endoscopic retrograde cholangiopancreatography (ERCP). However, its usefulness and safety are controversial in elderly patients. Our aim was to assess the safety and usefulness of CO2 insufflation during ERCP in elderly patients. METHODOLOGY: Between April 2010 and June 2011, a total of 60 patients 75 years old or older, who underwent ERCP, were randomized into the CO2 group (n = 30) and the air group (n = 30). Main outcomes were determined by assessing abdominal symptoms according to the Wong-Baker FACES Pain Rating Scale, calculating the volume of residual gas retention within the intestines on abdominal X-ray quantitatively and observing the cardiopulmonary states. RESULTS: 30 patients in the CO2 group and 30 patients in the air group were analyzed. Abdominal distension (P < 0.01), discomfort (P < 0.01) and nausea (P < 0.01) at 2 hours after ERCP were significantly reduced in the CO2 group. The gas volume scores immediately after ERCP (P < 0.01) and at 2 hours (P < 0.01) were significantly lower in the CO2 group. CONCLUSIONS: CO2 insufflation instead of air insufflation is safe and useful for the prevention of post-ERCP abdominal symptoms in elderly patients.

[Endoscopic treatment for hemorrhagic peptic ulcer in patients aged 70 years or more].

In this study on endoscopic hemostasis in patients aged 70 years or older with gastrointestinal ulcer bleeding, presence of shock, volume of transfusion over 6 units, and ulcer size over 3cm and solitary ulcer were significant risk factors for rebleeding. For 30-day mortality, concomitant disease and inpatient status were significant risk factors. Based on these results, we consider elderly patients with the above risk factors as high-risk patients for rebleeding or fatal outcome. The purpose of this study was to evaluate the efficacy of prevention of rebleeding such as by combined hemostatic methods and scheduled second-look endoscopy, and also to evaluate the offers of multidisciplinary approach such as interventional radiology for decreasing of mortality. Our conclusion is that we were able to reduce rebleeding rate and mortality after endoscopic hemostasis in high-risk patients and implement strategy to provide more careful endoscopic management with a multidisciplinary approach.

Preoperative endoscopic pancreatic stenting for prophylaxis of pancreatic fistula development after distal pancreatectomy.

BACKGROUND AND OBJECTIVE: Pancreatic fistula is a common complication of distal pancreatectomy (DP). Although various surgical procedures have been proposed for DP in an attempt to decrease the high incidence of pancreatic fistula, the prevention of pancreatic fistula remains a major problem in DP. Endoscopic pancreatic stenting for the treatment or prophylaxis of such a fistula has been rarely described. METHODS: We reviewed 9 patients who underwent preoperative endoscopic pancreatic stenting for the prophylaxis of pancreatic fistula development after DP. RESULTS: Preoperative endoscopic pancreatic stenting was successfully performed with a 7F stent in all the 9 patients. Two patients, both with intraductal papillary mucinous tumor, developed mild acute pancreatitis after the stent placement. None of the 9 patients developed pancreatic fistula. The pancreatic stent was removed from 8 to 28 days (mean 11 days) postoperatively. CONCLUSIONS: Preoperative endoscopic pancreatic stenting may be an effective prophylactic measure against pancreatic fistula development following DP in selected patients.

Key factors for successful en bloc endoscopic submucosal dissection of early stage gastric cancer using an insulation-tipped diathermic knife.

BACKGROUND/AIMS: En bloc endoscopic mucosal resection (EMR) is presently considered to be the treatment of choice for endoscopically resectable early stage gastric cancer (EGC). Although a new EMR technique using an insulation-tipped diathermic knife (endoscopic submucosal dissection using an IT knife: IT knife-ESD) is reportedly suitable for en bloc resection, a failure in en bloc resection (piecemeal resection) can occur. We retrospectively analyzed factors affecting the success rate of en bloc resection by IT knife-ESD. METHODOLOGY: A total of 71 gastric lesions were treated by IT knife-ESD. En bloc/piecemeal resection rates were investigated. Twelve potential factors associated with clinicopathological characteristics or procedures were analyzed univariately and multivariately. RESULTS: IT knife-ESD was successfully performed in all 71 lesions. En bloc resection was achieved in 63 lesions (91%), while eight lesions (9%) were removed as two or more fragments (piecemeal resection). The multivariate analysis identified only one independent factor affecting the success rate of en bloc resection: the second-half period of procedure application. The en bloc resection rate was not associated with the tumor location/site, tumor size, specimen size, and ulceration within the tumor. CONCLUSIONS: Much experience with IT knife-ESD may resolve the tumor-related technical difficulties. It is true for this advanced procedure that endoscopist experience is highly likely to be a critical factor for treatment success. We consider that IT knife-ESD for EGC is feasible and safe when performed by experienced endoscopists.

Effect of oral branched chain amino acid-rich nutrient administered during endoscopic injection sclerotherapy of cirrhotic patients.

Endoscopic injection sclerotherapy (EIS) is conducted to treat esophageal varices associated with liver cirrhosis. Cirrhotic patients have protein energy malnutrition (PEM), and their malnutrition is aggravated during EIS due to dietary restrictions. The aim of this study was to evaluate the dietetic benefits of oral branched chain amino acid-rich nutrient (BCAA-rich nutrient) administered during EIS. Cirrhotic patients admitted for prophylactic EIS were divided into three groups: Group A given a general liquid nutrient in two divided doses, Group B given a BCAA-rich nutrient in two divided doses, and Group C given the BCAA-rich nutrient in four divided doses. The nutritional state was evaluated based on physical examinations, biochemical parameters, and indirect calorimetry. A total of 29 patients were enrolled. Blood biochemical examinations showed a significant increase in the Fischer's ratio in Groups B and C. Group B showed significant decreases in resting energy expenditure/basal metabolic rate, while Group C showed a significant rise in non-protein respiratory quotient. The oxidation rate of carbohydrate significantly increased and that of fat significantly decreased in Group C. Administration of the BCAA-rich nutrient is considered to be useful in improving abnormalities of energy metabolism during EIS.

En bloc endoscopic mucosal resection of a large early stage gastric cancer by combined use of an insulation-tipped diathermic knife and a grasping forceps percutaneously inserted into the gastric lumen.

A new endoscopic mucosal resection using an insulation-tipped diathermic knife (IT knife-EMR) is a promising procedure for en bloc resection of an early stage gastric cancer. However, the use of this procedure for a large lesion on the greater curvature of the gastric middle-upper body is technically difficult. With the help of a grasping forceps percutaneously inserted into the gastric lumen, which allowed traction to be applied to the lesion, a 66-year-old man with a large tumor (49mm in diameter) on the greater curvature of the gastric middle body underwent IT knife-EMR. This approach enabled easy dissection between the submucosa and the muscle layer by the IT knife under direct vision. The lesion was completely removed as a single piece. This new technique, employing IT knife-EMR in cooperation with a percutaneously inserted grasping forceps, could be a potential procedure to make original IT knife-EMR easier. This approach may enhance the utility of original IT knife-EMR for selected tumors, that is, large tumors on the greater curvature of the middle-upper body of the stomach and/or ulcerated tumors. We propose that the present approach may provide an important alternative to laparoscopic intragastric surgery.

[Some problems during esophagogastroduonenoscopy for elderly patients].

Esophagogastroduonenoscopy(EGD) is a useful tool not only for diagnostic examination but also for less invasive treatment. However, it is the well-known fact that complications occur during EGD, particularly in elderly patients. We reviewed EGD performed for elderly patients. Arrhythmia, elevated blood pressure over 50 mmHg, increased the pulse rates and decreased of oxygen saturation during EGD were more common in elderly patients. Changes in these parameters occurred more frequently when EGD passed through the pharynx at the time of insertion. In conclusion, EGD for elderly patients should be performed more gently and carefully, particularly at the time of insertion.

Effect of lansoprazole on the epigastric symptoms of functional dyspepsia (ELF study): A multicentre, prospective, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Since the publication of the Rome III criteria for functional dyspepsia (FD), the evidence about the efficacy of half-dose of proton pump inhibitors for dyspepsia symptoms have been limited. OBJECTIVE: To examine the efficacy of lansoprazole for functional dyspepsia (FD) diagnosed with the Rome III criteria by the multicentre, double-blind, randomized, placebo-controlled study in Japan. METHODS: A total of 54 FD participants were randomized to lansoprazole 15 mg once daily or placebo for a 4-week double-blind treatment period. The primary efficacy endpoint was an overall dyspeptic symptom relief rate evaluated by 5-point Likert scale scores. The alteration of dyspeptic symptom scores during the study period was also assessed. RESULTS: At week 4, the overall dyspeptic symptom relief rates were higher in the lansoprazole group (30.4%) than in the placebo group (6.7%) (p = 0.045). The scores for epigastric pain (p = 0.045) and epigastric burning (p = 0.03) were significantly improved in the lansoprazole group compared to the placebo group, whereas the improvement of the scores for postprandial fullness (p = 0.81) and early satiation (p = 0.33) was not different between lansoprazole and placebo groups. CONCLUSIONS: Lansoprazole 15 mg ameliorates dyspeptic symptoms, particularly the epigastric pain syndrome-related symptoms of FD.

Resection area of 15 mm as dividing line for choosing strip biopsy or endoscopic submucosal dissection for mucosal gastric neoplasm.

BACKGROUND: Endoscopic mucosal resection (EMR) is effective treatment for mucosal gastric neoplasm. Endoscopic submucosal dissection (ESD), a novel EMR method, has been reported to enable en bloc resection more frequently than conventional EMR methods such as strip biopsy (SB). However, ESD requires more time than SB. A small lesion can be resected en bloc and effectively treated with SB. GOAL: To evaluate using a 15 mm resection area as the dividing line between SB and ESD prospectively. STUDY: SB was applied for resection area less than 15 mm (SB group) and ESD for 15 mm or larger resection (ESD group). We compared characteristics of lesions and outcomes of EMR between the 2 groups. RESULTS: Ninety lesions were prospectively assigned to SB group (36 lesions) and ESD group (54 lesions). The average neoplasm size was 9.0+/-3.9 mm in the SB group and 19.1+/-11.3 mm in the ESD group (P<0.01). The average resection time was 11.7+/-5.8 minutes in the SB group and 128.9+/-102.8 minutes in the ESD group (P<0.01). The complete resection rate was 91.6% in the SB group and 83.3% in the ESD group (P=0.25). The complication rate was not significantly different between SB group and ESD group (11.1% vs. 16.7%, P=0.12). During follow-up (median 23+/-5 mo), 1 patient in each group, who had piecemeal resection at original EMR had recurrent neoplasm. CONCLUSIONS: Gastric mucosal neoplasms which require only small (<15 mm) resection can be treated with SB, as effectively as with ESD.

New guide wire technique for stent placement through an occluded self-expandable metal stent: The hairpin technique.

BACKGROUND AND AIMS: Self-expandable metal stents (SEMS) for malignant biliary strictures sometimes occlude, requiring the insertion of another stent. When a guide wire is advanced conventionally through the proximal portion of an occluded SEMS, the guide wire sometimes penetrates the stent mesh. The present study reports a new guide wire insertion technique that prevents this problem from occurring. METHODS: In this new method of advancing a guide wire, the tip is not straight but bent into a curve. Because the advancing end of the guidewire is rounded like a hairpin, it cannot penetrate the stent mesh. Before cannulation, the flexible tip of the guide wire is extended out of the tip of the cannula in the descending duodenum and then cannulation is carried out as the flexible tip makes a hairpin curve. The guide wire with a maintained hairpin curve is advanced through the proximal end of the SEMS. The hairpin curve pops open and the guide wire straightens out when the guide wire has passed through the SEMS. After that, a second stent can be inserted over the guide wire. This technique has been utilized 14 times for occluded SEMS in 10 patients between June 2001 and September 2003. RESULTS: In all patients the technique served to ensure access to the biliary tree and successful placement of a second stent. CONCLUSIONS: This new hairpin guide wire technique was effective in preventing the guide wire from penetrating the stent mesh and, therefore contributed to successful stent placement within occluded SEMS.

Differential diagnosis of benign versus malignant nonfunctioning islet cell tumors of the pancreas: the roles of EUS and ERCP.

BACKGROUND: Differentiation between benign and malignant nonfunctioning islet cell tumors of the pancreas before surgery is often difficult. The roles of EUS and ERCP were evaluated in the differential diagnosis of these tumors. METHODS: Seven patients with histologically confirmed nonfunctioning islet cell tumors (4 benign, 3 malignant) underwent EUS and ERCP. OBSERVATIONS: EUS demonstrated a homogeneous hypoechoic mass or a hypoechoic mass with a regular central echogenic area in the 4 cases of benign tumor, and a hypoechoic mass with an irregular central echogenic area in all 3 cases of malignant tumor. The irregular central echogenic area corresponded to severe hemorrhage, necrosis, or fibrosis with hyalinosis (hyaline degeneration) on pathologic examination. ERCP demonstrated displacement or complete obstruction (because of ductal invasion) of the main pancreatic duct in 2 patients with malignant tumors and no abnormalities in the other 5 cases. CONCLUSIONS: In patients with nonfunctioning islet cell tumors, a hypoechoic mass with an irregular central echogenic area on EUS or complete obstruction of the main pancreatic duct on ERCP suggests malignancy.

Endoscopic hemostasis: safe treatment for peptic ulcer patients aged 80 years or older?

BACKGROUND AND AIM: Recently, the number of peptic ulcer patients aged 80 years or older has been increasing. However, little information is available concerning therapeutic endoscopy for these patients. The objective of this study was to evaluate the efficacy of endoscopic hemostasis for peptic ulcer bleeding in patients aged 80 years or older. METHODS: In this 7-year study, bleeding peptic ulcer patients were divided into group A (>/=80 years old) and group B (<80 years), for which prospective data, endoscopic findings and outcomes of endoscopic treatment were compared. RESULTS: Of the 459 patients who underwent endoscopic hemostasis for peptic ulcer bleeding, the 42 patients (average age 84 +/- 3 years) in group A had a significantly higher incidence of concomitant disease, lower hemoglobin, transfusional requirement over 800 mL and lower serum albumin than the 417 patients (average age 55 +/- 13 years) in group B. Significantly more patients in group A had large gastric ulcers. More patients in group A had ulcers located at the proximal third of the stomach, which is technically difficult to treat endoscopically. Nevertheless, all patients in groups A and B underwent initial hemostasis successfully. The rebleeding rate was not significantly different between group A and B. Neither group had hospital deaths nor complications related to endoscopic procedures. CONCLUSIONS: Endoscopic hemostasis for peptic ulcer bleeding in patients aged 80 years or older is effective and safe. Increasing age may no longer be a risk factor for rebleeding and hospital death after endoscopic hemostasis for peptic ulcer bleeding.

Short-term and long-term benefits of endoscopic hemoclip application for Dieulafoy's lesion in the upper GI tract.

BACKGROUND: Dieulafoy's lesion is an important cause of GI bleeding. The results of hemoclip application as the first treatment of choice for Dieulafoy's lesions have not been reported. This study prospectively examined the short- and long-term outcomes of hemoclip application for Dieulafoy's lesions. METHODS: The study was conducted over a 7-year period beginning in January 1995 during which hemoclip application was used as the first-choice hemostatic treatment for Dieulafoy's lesions. Clinical data, endoscopic findings, and outcome of treatment were evaluated. Long-term outcome for patients was also investigated. RESULTS: A Dieulafoy's lesion was diagnosed in 34 patients (27 men, 7 women; mean age, 54 years, range 21-81 years) after a mean of 1.2 endoscopies; 79.4% of the patients had active bleeding. Initial hemostasis was attained by hemoclip placement in 94.1%. The rate of recurrent bleeding was 9.3%. No patient required additional treatment such as surgery. The 30-day mortality rate was 2.9% (1 death, unrelated). For the remaining 33 patients, median follow-up was 53.8 months (range 19 to 90 months). Another Dieulafoy's lesion developed in one patient during follow-up, but in a different location compared with the index lesion. CONCLUSIONS: Endoscopic hemoclip application for Dieulafoy's lesions was effective and safe with short- and long-term benefits.