Hiroki Fukuma

Papillary dilation vs sphincterotomy in endoscopic removal of bile duct stones. A randomized trial with manometric function.

To circumvent the long-term effects of papillary ablation for extracting common bile duct stones (<12 mm in diameter) in endoscopic sphincterotomy (EST), endoscopic papillary dilation (EPD) was attempted in 20 patients. To evaluate papillary function before and after the procedures, manometry of the sphincter of Oddi was carried out in 13 with EPD and 10 of 20 patients with EST. Extraction of all stones was successful (100%) in both groups at an equal rate. Repeated numbers of procedures were common in both groups. However, the mean duration of the procedure was high in EPD compared to EST (63 min vs 42 min,P<NS). Adjunctive therapies like mechanical lithotripsy (ML), nasobiliary drainage, and choledochoscopy were included in EPD, while EST required a basket catheter and ML. There was no significant difference on manometry before and after the procedures (P=NS), although papillary function was found to have decreased after the EPD. In contrast, all patients in the EST group lost papillary function after the procedure. Thirty-day morbidity and mortality rate were absent in both groups. Immediate and 2.5-year follow up complications were uncommon in both groups. As a simple method, EPD may be an effective and safe alternative to EST in the management of patients with bile duct stones who require maintenance of papillary function.

Usefulness of single and repetitive percutaneous transhepatic gallbladder aspiration for the treatment of acute cholecystitis

BackgroundThe aim of this study was to evaluate the safety and usefulness of single and repetitive percutaneous transhepatic gallbladder aspiration (PTGBA) for the treatment of acute cholecystitis.MethodsPTGBA was performed in patients with acute cholecystitis who showed no improvement after treatment with broad-spectrum antibiotics. PTGBA was carried out at bedside. When the bile was too thick to be aspirated through a 21-gauge needle, an 18-gauge needle was used. Aspiration of the gallbladder contents and injection of antibiotics into the gallbladder were performed without the placement of a drainage catheter. When improvement was not observed after the first attempt, PTGBA was repeated.ResultsSingle PTGBA achieved improvement in 32 of 45 patients. In 11 of the remaining 13 patients, the second PTGBA was effective. In the remaining two patients, repetitive PTGBA was not carried out because of advanced cancer. In two of 45 patients, 18-gauge needles were necessary for PTGBA because of the high viscosity of the bile. PTGBA was carried out in three patients with blockage of the cystic duct by a stent, and it was effective in all three. Two patients whose conditions improved with a single PTGBA experienced a recurrence at 4 and 31 months, respectively, after PTGBA. No other severe complications related to PTGBA were observed in any patients.ConclusionsFor the treatment of acute cholecystitis that does not react to conservative therapies, PTGBA is a safe, simple, and effective treatment modality that can be performed at bedside without any severe complications.

Estimation of the stent placement above the intact sphincter of Oddi against malignant bile duct obstruction

BackgroundIn endoscopic biliary stenting against malignant biliary obstruction, stent blockage remains as an important problem. Stent blockage occurs as a result of bacterial adherence to the inner wall of the stent. We evaluated the stent placement above the intact sphincter of Oddi to retain the function of the sphincter of Oddi as a bacteriological barrier.MethodsSixteen patients with malignant biliary obstruction were assessed as the patients with the stent above the intact sphincter of Oddi. Sixteen patients with malignant biliary obstruction were assessed as the patients with the conventional stent placement across the sphincter of Oddi. Tannenbaum 10-Fr. stents were used in both the groups.ResultsThe median patency periods of the stent were 255 days (25th to 75th percentiles, 212–454 days; range, 39–454 days) for the group of the stents placed above the sphincter of Oddi and 82 days (25th to 75th percentiles, 48–131 days; range, 22–196 days) for the group of the stents placed across the sphincter of Oddi, respectively, with significant difference (P = 0.0001). The occlusion rates of stents placed above and across the sphincter of Oddi were 37.5% and 93.8%, respectively, with significant difference (P = 0.0008). The dislocation rates of the stent were 0% and 6.3%, respectively (not significant).ConclusionsPlacement of the stent above the intact sphincter of Oddi was associated with longer stent patency and lower occlusion rate.

Concomitant colitis associated with primary sclerosing cholangitis.

Between 1985 and 2001, seven Japanese patients (four males and three females) were diagnosed as having primary sclerosing cholangitis (PSC) in our hospital. All seven patients received total colonoscopy with distal ileoscopy. All four male patients were diagnosed as having colitis by colonoscopy, while none of the three female patients had colitis. The four patients with colitis did not have any symptoms attributable to colitis, such as diarrhea or hematochezia. In three of the four patients, unclassified colitis was the most suitable diagnosis, because there were no typical findings of ulcerative colitis or Crohns disease. The remaining patient was diagnosed as having eosinophilic colitis. By colonoscopic visualization, the right-sided colon, including the terminal ileum, was mainly involved, but the lesions were not severe. The main findings were redness, erosion, stenosis, and insufficiency of haustral formation. Histologically, these lesions were nonspecific inflammatory changes in the three patients with unclassified colitis. In the patient with eosinophilic colitis, remarkable infiltration of eosinophils was observed. Thus, unclassified colitis appeared to be the main complication in these patients with PSC. Males predominated in regard to concomitant colitis, and they had no symptoms of the colitis. Colonoscopic examination revealed that the lesions were not severe. The main lesions were found in the right-sided colon, with nonspecific inflammatory changes. These results suggest that colonoscopic surveillance of patients with PSC should be performed even if they do not have any colitis symptoms.

Interferon-γ, interleukin (IL)-2 and IL-2 receptor expressions in hepatitis C virus-infected liver

SummaryCytokine response to viral infection can be of critical importance in the host defense against virus. Interferon (IFN)-γ and interleukin (IL)-2 have wide ranges of activities in host defense mechanisms. Therefore, these cytokine genes in the liver were investigated in a series of patients with hepatitis C virus (HCV) infection using a reverse transcribed-polymerase chain reaction (RT-PCR). Total RNA was purified from liver biopsies, reverse transcribed to cDNA, amplified by specific primers, and the products were detected by agarose gel and slot blot hybridization. All samples from acute hepatitis (AH; n=4) and chronic hepatitis patients (CH; n=19) were positive for IFN-γ at varying degrees. AH patients showed strong signals compared to CH patients, liver cirrhosis (LC; n=12; 72% positive) patients, and hepatocellular carcinoma (HCC; n=21; 19% positive) patients. IL-2 gene was undetectable in all patients tested. IL-2 receptor (IL-2R) was detectable in AH, CH and LC patients but not in HCC patients. We conclude that IFN-γ has important roles in the cytokine network that indeed present in the liver of HCV patients while the presence of IL-2R gene may indicate that the signaling pathway for IL-2 is intact.

Combination of assay of human telomerase reverse transcriptase mRNA and cytology using bile obtained by endoscopic transpapillary catheterization into the gallbladder for diagnosis of gallbladder carcinoma

OBJECTIVES:It is difficult to make accurate diagnoses of polypoid lesions in the gallbladder. To increase the diagnostic accuracy, we have developed an endoscopic technique to obtain gallbladder bile, termed endoscopic transpapillary catheterization into the gallbladder (ETCG). We evaluated the usefulness of a molecular biological approach to the diagnosis of gallbladder carcinoma, in which gallbladder bile obtained by the ETCG technique is used.METHODS:Twenty patients undergoing an operation because of suspicion of gallbladder carcinoma were enrolled. Twelve patients were confirmed to have gallbladder carcinoma, and four were found to have chronic cholecystitis. Two patients with polypoid lesion were diagnosed as having an inflammatory polyp and a hyperplastic polyp, respectively. The remaining two patients with polypoid lesions were diagnosed as having a cholesterol polyp. Gallbladder bile collected by the ETCG technique was evaluated cytologically and also analyzed for telomerase activity and mRNA for human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. In 14 patients, hTERT mRNA in resected specimens (fixed in 10% formalin and embedded in paraffin) was also examined.RESULTS:Cytology of gallbladder bile was positive in eight of 11 examined patients (72.7%) with gallbladder carcinoma. hTERT mRNA was detectable in gallbladder bile as well as in resected neoplastic tissues in four of 12 patients (33.3%) with carcinoma. Conversely, telomerase activity was negative in all eight examined patients with carcinoma. Overall, either cytology or hTERT mRNA of gallbladder bile was positive in 10 of 12 patients (83.3%) with gallbladder carcinoma. Cytology, hTERT mRNA, and telomerase activity were negative in eight patients with benign disease.CONCLUSIONS:The combination of cytology and hTERT mRNA analysis of gallbladder bile might be helpful for the preoperative diagnosis of gallbladder carcinoma.

Pre-cutting using a noseless papillotome with independent lumens for contrast material and guidewire

Background:  The technical success of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) depends on selective cannulation into the bile duct. We have developed a new type of precut papillotome for selective cannulation.

Direct dissolution of gallstones with methyl tert-butyl ether (MTBE) via endoscopic transpapillary catheterization in the gallbladder (ETCG)

In a pilot study of direct dissolution therapy of gallstones with methyl tert-butyl ether (MTBE), endoscopic transpapillary catheterization in the gallbladder (ETCG) was performed. Complete dissolution was seen in 8 out of 12 (66%) patients and partial dissolution was seen in 2 (16%) patients. In one of the 8 complete dissolution patients, combined extracorporeal shock wave lithotripsy (ESWL) and dissolution therapy was carried out successfully. These 8 patients were followed up for 12–20 months with regular ultrasonography. During this period, 1 patient underwent laparoscopic cholecystectomy due to stone recurrence. Thickening of the gallbladder wall was seen in 2 patients, but there were no other complications. Using Tsuchiyas classification based on ultrasound, complete dissolution was seen in type Ia stones. This pilot study suggests that the direct dissolution of gallstones with MTBE via ETCG might be a useful and safe non-invasive treatment in patients with cholesterol stones in preserved gallbladders.

Increased expression of cytokines in liver and serum in patients with extrahepatic diseases.

To determine whether the liver plays an immunological role in certain extrahepatic disorders, we investigated the expression of interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α in 11 patients who had recovered from cholecystolithiasis, 12 patients with gastric cancer, 20 patients with chronic hepatitis, and 6 healthy controls. Cytokine mRNAs in the liver were detected by semiquantitative reverse transcribed-polynerase chain reaction. Serum cytokines and soluble IL-2 receptor (sIL-2R) were investigated by enzyme-linked immunosorbent assays. Increases in TNF-α, IL-6, IL-1β, and IFN-γ mRNAs were found in the livers of patients with extrahepatic diseases. TNF-α and IL-6 peptides were increased in the sera of patients with gastric cancer. TNF-α in the sera and TNF-α mRNA in the liver were correlated in gastric cancer patients. Surprisingly, sIL-2R in the serum of gastric cancer patients was significantly higher than the level in healthy controls. Our findings suggest that the liver produces cytokines in reaction to extrahepatic lesions. Further, the increase in sIL-2R in gastric cancer patients indicates that malignancy may affect the immune network in vivo.

Abnormal bile flow in patients with achalasia

Background: It has been reported that esophageal achalasia is frequently associated with the dysmotility of other digestive organs. However, the prevalence of extraesophageal complications in patients with achalasia still remains poorly understood. We performed cholescintigraphy, using 99mTc-pyridoxyl-5-methyl-tryptophan, in patients with esophageal achalasia to assess any possible dysfunction of the sphincter of Oddi associated with achalasia. Methods: Eight patients (two men and six women) were examined to determine the time required for bile to flow from the bile duct to the duodenum. Results: Excretion time of bile was markedly prolonged in five of the eight patients with achalasia. Scintigraphic findings were not correlated with the radiographic classification of achalasia or with the grading of achalasia. Conclusions: The present results suggest that a considerable number of patients with achalasia have dysfunction of the sphincter of Oddi, irrespective of the morphological type of achalasia and the grade of esophageal dilatation.