Evaluation of magnifying endoscopy using narrow band imaging using ex vivo bile duct (with video).

BACKGROUND AND AIM: Detailed endoscopic findings of the bile duct mucosa, even of the non-neoplastic mucosa, have not yet been established. The aim of the present study was to compare a currently used video cholangioscope (CCS) with a magnifying endoscope (ME) that is commonly used for the gastrointestinal tract, for visualization of the bile duct mucosa. METHODS: Ten freshly resected common bile ducts were used in this study. We observed the non-neoplastic bile duct mucosa with CCS and ME, and carried out both conventional white light imaging and narrow band imaging. After histological diagnosis, the 10 specimens were classified into three categories according to the degree of histological inflammation: normal to mild, moderate, and severe. Then, we examined the relationship between the magnifying endoscopic findings and the histopathological findings. RESULTS: In eight of the 10 cases, the visualization obtained with CCS was inferior to that obtained by ME. Five specimens were classified as normal to mild inflammation, and many oval-shaped, depressed areas and a fine, regular network of the microvessels were observed by ME on the mucosal surfaces of these specimens. The remaining specimens were classified as moderate or severe inflammation, and the aforementioned findings could not be clearly visualized. CONCLUSION: CCS does not allow visualization of the bile duct mucosa with high sensitivity. Oval-shaped depressed areas and a fine, regular network of microvessels are characteristic endoscopic features of non-neoplastic bile duct mucosa without inflammation.

A case of acute pancreatitis following endoscopic biopsy of the ampulla of Vater.

Ampullary tumors are diagnosed by endoscopic biopsy of the ampulla of Vater. We encountered a rare case of acute pancreatitis following endoscopic biopsy of the ampulla. A 53-year-old man referred to our hospital for detailed examination of a suspected tumor of the ampulla of Vater. We conducted endoscopic biopsy from the ampulla. He developed severe abdominal pain four hours after the procedure. The serum amylase and serum lipase were elevated and abdominal computed tomography (CT) revealed pancreatic enlargement and diffuse stranding of the peri-pancreatic fat, compatible with the findings of acute pancreatitis. We diagnosed the patient as having acute pancreatitis caused by endoscopic biopsy of the ampulla of Vater. Conservative therapy improved his condition, however, a large pancreatic walled-off necrosis (WON) developed. Therefore, we performed endoscopic ultrasonography (EUS)-guided cyst drainage on the 74th day after admission. The WON diminished gradually in size and the symptoms disappeared, and the patient was discharged in good physical condition on the 137th day after admission. In this case, the ampullary biopsy may have caused mucosal edema or intraductal hematoma, resulting in pancreatic duct obstruction. It is important for endoscopists both to be aware of this potential complication following endoscopic biopsy of the ampulla and to inform the patients about possible complications of this procedure.

The utility of a novel antibody in the pathological diagnosis of pancreatic acinar cell carcinoma.

AIMS: Acinar cell carcinomas (ACCs) are rare tumours of the exocrine pancreas accounting for about 1-2% of all pancreatic neoplasms in adults. It is therefore difficult to come across a large number of ACC cases in a single medical institution, and only a few serial studies have been published. Since ACCs present a wide variety of morphological patterns, immunohistochemical analysis is useful. In this study, the authors established a novel monoclonal antibody 2P-1-2-1 by means of a subtractive immunisation method. METHODS: Immunohistochemical staining was performed using 50 primary pancreatic tumors, including 7 ACCs, 7 neuroendocrine tumours (NETs), 5 solid-pseudopapillary neoplasms (SPNs), and 31 ductal carcinomas and organs other than the pancreas. RESULTS: Non-neoplastic acinar cells were stained diffusely, but epithelial cells of the pancreatic duct and the islets of Langerhans were not stained. In pancreatic tumours, all the seven ACCs were diffusely positive for the 2P-1-2-1 antibody. However, no positive staining was found in other pancreatic tumours including NETs, SPNs and ductal adenocarcinomas. The sensitivity and specificity of the 2P-1-2-1 antibody for ACCs were both 100%. In other organs studied, positive staining was observed only in the ectopic pancreas. CONCLUSIONS: It was shown that the 2P-1-2-1 antibody specifically stained the pancreatic acinar cells and tumours of acinar cell origin, such as ACCs. Although it remains unclear at this time to which proteins the monoclonal antibody 2P-1-2-1 is directed, it is suggested to be useful for the pathological diagnosis of ACCs and for the exclusion of other pancreatic tumours.

Serum immunoglobulin G4 associated with number and distribution of extrapancreatic lesions in type 1 autoimmune pancreatitis patients.

BACKGROUND AND AIM: Type 1 autoimmune pancreatitis (AIP) is characterized by the increase of serum immunoglobulin (Ig)G4 and abundant IgG4 plasma cell infiltration in the pancreas and various extrapancreatic lesions (EPL), which are proposed as IgG4-related disease. We assessed the correlation between serum IgG4 and the number of EPL, and the association between serum IgG4 and the distribution of EPL in type 1 AIP patients. METHODS: Serum IgG4 was measured in 35 type 1 AIP patients and 71 non-AIP patients. The clinical characteristics and distribution of eight EPL were determined in 35 type 1 AIP patients. RESULTS: Serum IgG4 in type 1 AIP was significantly higher than in non-AIP (P < 0.001). A total of 33 patients had EPL among 35 patients with type 1 AIP (94.3%). There was a significant correlation between serum IgG4 and the number of EPL (ρ = 0.75, P < 0.001). Further, to assess the association between serum IgG4 and the distribution of EPL, type 1 AIP patients were divided into two groups: as abdominal localized EPL and systemic EPL. Both serum IgG4 and total numbers of EPL in systemic EPL were remarkably higher than those in abdominal localized EPL. Serum IgG4 cut-off value was 346 mg/dL to distinguish between abdominal localized EPL and systemic EPL according to the receiver-operator characteristic curve data. CONCLUSIONS: Our findings indicated that serum IgG4 was useful in both the diagnosis of type 1 AIP and the detection of systemic EPL. Our finding may help the concept and diagnostic criteria of IgG4-related disease with type 1 AIP.

Endoscopic ultrasonographic study of autoimmune pancreatitis and the effect of steroid therapy.

BACKGROUND: Recently, endoscopic ultrasonography (EUS) has been used for the diagnosis of chronic pancreatitis (CP); however, EUS diagnosis of autoimmune pancreatitis (AIP) varies among different researchers. We investigated EUS findings in AIP and retrospectively analyzed them before and after steroid therapy. PATIENTS AND METHODS: The subjects were 32 patients with AIP and the EUS images of the pancreatic parenchyma were evaluated with reference to the Sahai criteria. Patients' background factors detected by EUS were analyzed statistically. Peroral steroid was given to 23 of the 32 patients. EUS was also performed 2 weeks after the initiation of therapy in 14 of the 23 patients, and the changes in EUS were investigated. Microscope images were compared with EUS images in one patient who underwent surgical resection. RESULTS: EUS results included hyperechoic strands in 26 (81.3%) and lobularity in 17 (53.1%) patients. The patients' background factors included the presence of splenic and/or portal vein occlusion or narrowing around the pancreas in patients who had neither hyperechoic strands nor lobularity (p = 0.002, p = 0.004). The numbers of EUS findings before versus after steroid therapy were 11 versus 5 for hyperechoic strands and 7 versus 2 for lobularity. Microscope images showed the coexistence of relatively well-maintained lobular structures of pancreatic acini and almost complete loss of such structures. CONCLUSION: EUS findings in AIP were similar to those in early-stage CP, and hyperechoic strands and lobularity seem to suggest a condition under which the histology of lobular structures of the pancreatic acini is relatively well-maintained. EUS results had improved within about 2 weeks of steroid therapy.

Molecular and histological characterization of primary (betaproteobacteria) and secondary (gammaproteobacteria) endosymbionts of three mealybug species.

Microscopic localization of endosymbiotic bacteria in three species of mealybug (Pseudococcus longispinus, the long-tailed mealybug; Pseudococcus calceolariae, the citrophilus mealybug; and Pseudococcus viburni, the obscure mealybug) showed these organisms were confined to bacteriocyte cells within a bacteriome centrally located within the hemocoel. Two species of bacteria were present, with the secondary endosymbiont, in all cases, living within the primary endosymbiont. DNA from the dissected bacteriomes of all three species of mealybug was extracted for analysis. Sequence data from selected 16S rRNA genes confirmed identification of the primary endosymbiont as "Candidatus Tremblaya princeps," a betaproteobacterium, and the secondary endosymbionts as gammaproteobacteria closely related to Sodalis glossinidius. A single 16S rRNA sequence of the primary endosymbiont was found in all individuals of each mealybug species. In contrast, the presence of multiple divergent strains of secondary endosymbionts in each individual mealybug suggests different evolutionary and transmission histories of the two endosymbionts. Mealybugs are known vectors of the plant pathogen Grapevine leafroll-associated virus 3. To examine the possible role of either endosymbiont in virus transmission, an extension of the model for interaction of proteins with bacterial chaperonins, i.e., GroEL protein homologs, based on mobile-loop amino acid sequences of their GroES homologs, was developed and used for analyses of viral coat protein interactions. The data from this model are consistent with a role for the primary endosymbiont in mealybug transmission of Grapevine leafroll-associated virus 3.

Development of intrahepatic cholangiocarcinoma after a 14-year follow-up of a patient with primary sclerosing cholangitis and ulcerative colitis.

Intrahepatic cholangiocarcinoma (ICC) is one of the life-threatening complications of primary sclerosing cholangitis (PSC). However, the incidence of ICC in Japanese PSC patients is low, and the association between the development of ICC and morbidity duration of PSC is largely unknown. Here, we describe a case of ICC that developed after a long-term follow-up of a patient with PSC and ulcerative colitis (UC). At the age of 10 years, the patient was first diagnosed with UC and its remission was achieved with systemic steroid therapy. Since then, he was routinely followed-up. At the age of 19 years, laboratory tests showed abnormalities in liver function parameters, and the patient was diagnosed with PSC. Although treatment with ursodeoxycholic acid improved the abnormalities in serum levels of biliary enzymes and no PSC-related symptoms were seen for 13 years, calculous cholecystitis frequently occurred in the patient since the age of 32 years. He developed ICC, which expressed some hepatic progenitor cell markers such as CD133, neural cell adhesion molecule, keratin 7, and keratin 19 at the age of 33 years. ICC was treated by curative partial hepatectomy and adjuvant chemotherapy with gemcitabine. Eight months later, however, the patient developed multiple metastases in the abdominal lymph nodes and lungs, and died 21 months after the onset of ICC. Here, we report a case of ICC that developed after a 14-year follow-up of a patient with PSC and UC.

Accuracy of differential diagnosis for pancreatic cancer is improved in the combination of RCAS1 and CEA measurements and cytology in pancreatic juice.

Improvement of diagnostic accuracy for pancreatic cancer in pancreatic disease patients was investigated by examining the combination of three diagnostic methods, i.e., measurements of RCAS1 and CEA levels in pancreatic juice and pancreatic juice cytology. Pancreatic juice was collected from 12 pancreatic cancer (PC) and 26 non-PC patients. RCAS1 and CEA levels were measured by using ELISA. RCAS1 expression on surgically resected tissue was immunohistochemically examined for 2 PC patients. By setting the cutoff level of RCAS1 at 10 U/ml and that of CEA at 18.5 µg/ml, sensitivity of RCAS1 was 42% and that of CEA was 50%. On the other hand, sensitivity and specificity increased from 42% and 85% of RCAS1 alone to 75% and 85% in the examination of RCAS1 + CEA + cytology, and the false-negative rate was also reduced to 25% in this combination. Immunohistochemically, a patient with a high RCAS1 level in pancreatic juice had numerous RCAS1-positive tumor cells in the pancreatic juice. We concluded that RCAS1 and CEA measurements together with cytology in pancreatic juice would be a useful combination method for making a differential diagnosis of PC from non-PC.

The management of the pancreatic cystic neoplasm: the role of the EUS in Japan.

Diagnosis of cystic lesions of the pancreas is made by clinical history taking, physical examination, blood biochemical tests and diagnostic imaging, such as transabdominal ultrasound, endoscopic ultrasound (EUS), cross-sectional imaging (computed tomography and/or magnetic resonance imaging) and endoscopic retrograde cholangiopancreatography, bearing in mind the known characteristic features of the various cystic lesions that can occur in this organ. Among others, EUS, endowed with a sharp local resolving power, has been described as a highly useful examination method, because it enables concurrent fine-needle aspiration (FNA). EUS has an important role in the differential diagnosis and tumor grading (benign, premalignant or malignant) of cystic lesions. Although the differential diagnosis of cystic lesions of the pancreas based on EUS morphology is practicable to some extent, there have also been reports showing that the diagnosis might vary with the endosonographer and that the diagnostic performance of this method for tumor grading is not necessarily high. In countries overseas, differential diagnosis and tumor grading of cystic lesions of the pancreas are actively undertaken not merely by EUS morphology, but also by cyst-fluid EUS-guided FNA (EUS-FNA) cytology and measurements of pancreatic enzymes and tumor markers, and importance is attached to EUS-FNA in the latest version of the American Society for Gastrointestinal Endoscopy Guideline and in the diagnostic strategies for cystic diseases of the pancreas. Meanwhile, the current Japanese consensus is that EUS-FNA is not recommended in cases of mucinous cystic lesions suspected as being intraductal papillary mucinous neoplasm or mucinous cystic neoplasm.

Direct cholangioscopy using a double-balloon enteroscope: choledochojejunostomy with intraductal biliary carcinoma.

A 75-year-old man who underwent choledochojejunostomy for gallstones 30 years ago was hospitalized for general malaise. Abdominal computed tomography revealed marked dilation of the intrahepatic bile duct in the right lobe and an image of a hypervascular tumor. Endoscopic retrograde cholangiography using double-balloon enteroscopy (DBE) showed a filling defect that was localized to the right hepatic bile duct. Furthermore, the scope was able to readily pass through the anastomosed site of the choledochojejunostomy and, therefore, we observed the interior of the bile duct using the same scope. We obtained an image showing a whitish, papillary-like tumor, and a biopsy of the tumor rendered the pathology of intraductal papillary mucinous carcinoma. Direct cholangioscopy using DBE is a useful diagnostic tool, particularly in patients with a past history of choledochojejunostomy.

Successful endoscopic extraction of a large impacted choledocholithiasis in the ampulla of vater: two interesting cases.

In patients with choledocholithiasis, a stone can sometimes become impacted in the ampulla of Vater, potentially resulting in the complications of acute cholangitis and acute pancreatitis. Endoscopic sphincterotomy and needle knife papillotomy are very effective for the removal of an impacted stone in the ampulla of Vater. Dramatic improvement of the symptoms may be expected if these procedures are performed sufficiently early after the occurrence of the impaction. However, depending on the size, site and situation of the impacted stone, we have often encountered difficulties during endoscopic treatment. We encountered two interesting cases of choledocholithiasis with impaction of large stones in the ampulla of Vater. In Case 1, treatment with radial incisions was added to the usual treatment of needle knife papillotomy, because of the large size of the stone, and the combined treatment was effective. In Case 2, a large periampullary choledochoduodenal fistula was created at the ampulla of Vater, and an indwelling double pigtail tube was placed in the ampulla; the stone then discharged via the tube without additional need for endoscopic sphincterotomy or needle knife papillotomy. Our experience in these cases indicates that innovations in treatment according to the situation of the impacted stone may be needed for the treatment of giant impacted stones in the ampulla of Vater.

Comparison of sclerosing cholangitis with autoimmune pancreatitis and infiltrative extrahepatic cholangiocarcinoma: multidetector-row computed tomography findings.

PURPOSE: The aim of this study was to compare multidetector-row computed tomography (MDCT) findings between cases of sclerosing cholangitis with autoimmune pancreatitis (SC-AIP) and infiltrative extrahepatic cholangiocarcinoma (IEC). MATERIALS AND METHODS: We retrospectively assessed MDCT findings from 16 IEC cases and 13 SC-AIP cases. MDCT findings were analyzed with regard to location, length, wall thickness, contour, stricture wall enhancement pattern, proximal duct diameter, and the presence of diffuse concentric thickening in the proximal duct and gallbladder wall thickness. RESULTS: Stricture length, stricture wall thickness, and proximal duct diameter were significantly smaller for SC-AIP than for IEC: 19.3 +/- 8.7 vs. 31.8 +/- 12.0 mm (P = 0.004), 2.1 +/- 1.3 vs. 4.1 +/- 1.3 mm (P < 0.001), and 9.2 +/- 3.9 vs. 13.3 +/- 5.0 mm (P = 0.012), respectively. SC-AIP was correlated with stricture location in both the intrapancreatic and hilar hepatic bile ducts, concentric stricture contour (P < 0.001), and diffuse concentric thickening of the proximal bile duct (P = 0.010). Overall values of sensitivity, specificity, and accuracy used to distinguish between SC-AIP and IEC for stricture wall thickness of <3.0 mm and concentric contour were 76.9%, 93.8%, and 86.2%, respectively, and 100%, 87.5%, 93.1%, respectively. CONCLUSION: Concentric contour and stricture wall thicknesses of <3.0 mm may help distinguish between SC-AIP and IEC.

Expression of various biotin-binding proteins in transgenic tobacco confers resistance to potato tuber moth, Phthorimaea operculella (Zeller) (fam. Gelechiidae).

The high affinity biotin-binding proteins (BBPs) avidin and streptavidin are established insecticidal agents, effective against a range of insect pests. Earlier work showed that, when expressed in planta, full length avidin and a truncated form of streptavidin are highly insecticidal. More recently, a wide range of BBPs, found in diverse organisms or engineered for various biotechnological applications have been reported. However, their effectiveness as plant-based insecticides has not been established. Here we report in planta expression of three different genes, designed to produce BBP variant proteins in the vacuole. The first was mature full length chicken avidin, the second a circularly permuted dual chain chicken avidin, and the third was an avidin homologue, a native bradavidin from Bradyrhyzobium japonicum. All three proteins were expressed in Nicotiana tabacum (tobacco). The transgenic tobacco lines were healthy, phenotypically normal and, when subjected to bioassay, resistant to the important cosmopolitan pest, potato tuber moth (Phthorimaea operculella) larvae at concentrations of ~50 ppm.

Trans-gastric endoscopic drainage using a large balloon for pancreatic necrosis and abscess - two case reports.

Reports on endoscopic treatment for pancreatic necrosis and pancreatic abscess have occasionally been published in recent years. Single treatments using endoscopic transpapillary or transumural drainage were originally used, but these were frequently changed to surgical therapy. In recent years, attempts have been made, such as the use of a combination of transmural and transpapillary approaches, the balloon dilatation of the cystgastrostoma, and a daily endoscopic necrosectomy and saline solution lavage, and the treatment results have thus been improved, even though the number of cases is low. We performed transmural endoscopic ultrasonography (EUS)-guided drainage without a necrosectomy in two cases with pancreatic necrosis and abscess, and treated cases in which a continuous closed lavage using a tube with a large diameter was effective, and we herein report our findings.

Endoscopic retrieval of migrated plastic stent into bile duct or pancreatic pseudocyst.

Proximally migrated biliary plastic stent and migrated stent in the pancreatic pseudocyst are relatively rare complications. A migrated stent causes poor drainage conditions, which leads to secondary complications such as infection, abscess, perforation and, moreover, becomes a foreign object in the body, and retrieval or re-stenting is therefore necessary. The retrieval of a migrated stent includes surgical, percutaneous and endoscopic approaches, and the most non-invasive method is endoscopic retrieval. However, because very few devices are exclusively designed for retrieval, the current situation is that the available devices are used while taking advantage of various ideas and techniques. From previously reported cases and our experiences of such cases, we herein describe the methods of endoscopic retrieval for stents that have migrated into a bile duct or pancreatic pseudocysts.

A case report of primary hepatic squamous cell carcinoma that remarkably responded to low dose arterial injection of anti-cancer drugs.

Primary hepatic squamous cell carcinoma is rare. In this case, a malignant lesion was detected in bilateral hepatic lobes by ultrasound sonography and computed tomography. The maximum tumor diameter was approximately 10 cm. Tumor tissue obtained by aspiration liver biopsy was diagnosed as poorly differentiated squamous cell carcinoma. In gallium radioisotope scanning, no focus was detected in any organs other than the liver. As therapy, anti-cancer drugs were administered via hepatic arterial infusion. The patient received 10 mg of cis-diaminedichloroplatinum (CDDP) and 250 mg of 5-fluorouracil (5-FU) for 5 days every week. The therapy was continued for 3 weeks, and the same doses of CDDP and 5-FU were given to the patient once per 2 weeks in the clinic. The intrahepatic tumor lesion began to decrease from the start of treatment, and had almost disappeared 8 months after. Recurrence of the liver tumor occurred at 12 months from the start of treatment. The patient was re-admitted and treated with the same anti-cancer drugs via hepatic arterial injection. However, the drugs showed remarkable effect no longer and she died in month 23. The treatment with chemotherapy via hepatic arterial injection for a patient with squamous cell carcinoma offered a favorable therapeutic effect.

Additional benefit of lamivudine treatment as a preventive therapy for hepatic encephalopathy in patients with decompensated liver cirrhosis associated with hepatitis B.

Lamivudine has previously been found to be effective not only in patients with compensated liver disease due to hepatitis B virus (HBV) but also in those with hepatic decompensation. However, long-term follow-up of patients with hepatic encephalopathy (HE) has not been previously reported. We describe a patient with recurrent HE associated with decompensated liver cirrhosis due to hepatitis B. After the initiation of treatment with lamivudine, manifestation of HE has not been observed for about 2 years and liver function has improved as well. This experience suggests that improved liver function using lamivudine may contribute to prevention from recurrence of HE.