Endoscopic ultrasound-guided ethanol injection in the pancreas in a porcine model: a preliminary study.

BACKGROUND AND AIM: Despite aggressive multimodal treatments, survival rates for patients with pancreatic cancer remain disappointing. Local progression is problematic, and minimally invasive procedures allowing locoregional control are needed. In this study, we attempted endoscopic ultrasound (EUS)-guided injection of ethanol into the pancreas. METHODS: Under EUS guidance, pure ethanol (2 mL) was injected into normal tissue of the pancreatic body in two anesthetized domestic pigs. Serum concentrations of amylase, aspartame aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase were measured before treatment and at 2 h, 48 h and 2 weeks after injection. Body weight and clinical signs were also observed. After the animals were euthanized, the pancreases were analyzed histologically. RESULTS: EUS imaging allows real-time surveillance of the injection procedure. Mild diarrhea was noted in one animal, but no other adverse effects were observed. No marked changes in laboratory tests were noted. Histologically, parenchymal necrosis extending over a wide area was seen without severe inflammation. CONCLUSION: EUS-guided ethanol injection in the pancreas seems to be technically simple. More detailed assessments of the safety and dose-effect relationship issues associated with this procedure are required.

An autopsy case of autoimmune pancreatitis.

CONTEXT: Autoimmune pancreatitis is an increasingly recognized type of chronic pancreatitis, but little is known about the long-term outcome of the disease. CASE REPORT: We report an autopsy case of autoimmune pancreatitis. The patient was an 81-year-old Japanese male. He was referred to our department with jaundice in February 1996. ERCP images revealed a severe stricture of the lower part of the common bile duct and irregular narrowing of the main pancreatic duct. A diagnosis of extrahepatic cholangiocarcinoma was made and endoscopic biliary drainage was performed. A stricture of the common bile duct and narrowing of the pancreatic duct had improved on ERCP images when a follow-up examination was performed in November 1998. He was followed up for chronic pancreatitis. The serum IgG and IgG4 levels were increased on serological examination. He died of interstitial pneumonia and congestive heart failure in May 2003. At the autopsy examination, fibrosis was found in the periductal, interlobular and intralobular parts of the pancreas. Focal atrophy of the acinar cells was also identified. There was little infiltration of inflammatory cells into the parenchyma or the stroma of the pancreas. These pathological findings were similar to those of 'conventional' chronic pancreatitis. CONCLUSION: We present an autopsy case of autoimmune pancreatitis which is a rare finding.

Cdx2 expression in pancreatic tumors: Relationship with prognosis of invasive ductal carcinomas.

We have previously reported that Caudal-related homeobox gene 2 (Cdx2) is a useful prognostic intestinal phenotypic marker for advanced gastric cancers. In this study, we examined Cdx2 expression and phenotype in pancreatic tumors. We evaluated 19 mucinous cystic tumors (MCTs), 17 intraductal papillary-mucinous tumors (IPMTs), and 41 invasive ductal carcinomas (IDCs) with regard to their gastrointestinal phenotype. The expression of Cdx2 was also assessed immunohistochemically. The lesions were phenotypically divided into 39 gastric (G type), 29 gastric and intestinal mixed (GI type), 3 intestinal (I type), and 6 null (N type) types, independent of the histopathological type. Most of the pancreatic tumors were thus judged to be the positive for gastric phenotypic members. Cdx2 nuclear staining demonstrated a close relation to the intestinal phenotypic expression in all three types (MCTs, IPMTs, and IDCs; p<0.05). In IDCs, Kaplan-Meier analysis of Cdx2 expression showed the Cdx2-positive group to have a significantly better outcome than their negative counterparts (p=0.015). In conclusion, our data suggest that Cdx2 might be necessary for intestinal phenotypic expression even in pancreatic tumor cells. In addition, Cdx2 expression in IDCs may be a novel prognostic marker for patient survival.

Pancreaticobiliary maljunction in monozygotic twins--a case report.

We experienced a case of pancreaticobiliary maljunction in monozygotic twins. While one of the twins suffered from gallbladder cancer with poor prognosis, the other was not associated with biliary malignancy. Ultrasonography, endoscopic ultrasonography, and magnetic resonance cholangiopancreatography are effective in diagnosis of this disorder before occurrence of biliary cancers. This case is not only of academic interest for familial occurrence, but also of clinical interest in the early detection of pancreaticobiliary maljunction.

Amelioration of cerulein-induced acute pancreatitis by 2,2'-dipyridyl in rats.

We studied the effect of iron chelators, 2,2'-dipyridyl and desferrioxamine, on cerulein-induced pancreatitis in rats. Acute pancreatitis was induced by a single subcutaneous injection of 100 micrograms/kg body weight of cerulein, which caused hyperamylasemia and edematous pancreatitis with neutrophilic infiltration. Blood samples were collected for determination of serum amylase values and the pancreas was removed for the histological examination 6 h after the cerulein injection. Intraperitoneal administration of a ferrous iron chelator, 2,2'-dipyridyl, prior to the cerulein injection resulted in amelioration of hyperamylasemia and histological abnormalities such as edema and inflammation but not of acinar cell vacuolization. In contrast, administration of a ferric iron chelator, desferrioxamine, did not show any beneficial effects. These results indicate that administration of 2,2'-dipyridyl ameliorates the pancreatitis induced by the supramaximal dose of cerulein.

Localization of the most severely dysplastic/invasive lesions and mucin phenotypes in intraductal papillary mucinous neoplasm of the pancreas.

OBJECTIVE: The aim of this study was to define the relevance of mural nodules (MNs) as a "direct" indicator of malignancy of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: Thirty-nine surgically resected IPMNs excluding obviously invasive carcinomas were examined. The distribution of the most severely dysplastic lesions was mapped on specimens. Immunohistochemical analysis for MUC1 and MUC2 was performed on sections containing the histologically predominant lesions and the most severely dysplastic areas. RESULTS: The presence of MNs correlated well with the histological grade of IPMN (P < 0.01); however, the most severely dysplastic lesions were associated with a flat/nonelevated area rather than MNs (78.9%). In the MUC1-positive subgroup, minimally invasive carcinoma was colocalized to MNs, whereas most severely dysplastic foci including minimally invasive carcinoma with components of mucinous and tubular adenocarcinoma were observed in the areas apart from MNs in the MUC2-positive and MUC1/2-negative subgroups, respectively. CONCLUSIONS: Although our data support the concept that MNs represent areas of higher-grade dysplasia within IPMN, development of invasive lesions from MNs may be limited to cases that are MUC1-positive. Careful attention should be paid to the emergence of invasive IPMN from flat foci in MUC2-positive and MUC1/2-negative cases.

Homeobox gene CDX2 inhibits human pancreatic cancer cell proliferation by down-regulating cyclin D1 transcriptional activity.

OBJECTIVES: Homeobox gene caudal related homeobox gene 2 (CDX2) is an intestine-specific tumor suppressor gene. This study is intended to investigate the effect of CDX2 expression on cell proliferation and cyclin D1 expression in pancreatic cancer cells. METHODS: Four pancreatic ductal adenocarcinoma cell lines (PancQGO-1, BxPC-3, MIAPaCa-2, CFPAC-1), 1 islet carcinoma cell line (QGP-1), and 1 adenosquamous carcinoma cell line (KP-3) were analyzed for CDX1 and CDX2 expression using real-time reverse transcription-polymerase chain reaction and Western blot analysis. Proliferation of pancreatic cancer cells was analyzed using WST-1 assay after CDX2 transfection. Luciferase assay was performed to examine the effects of CDX2 on cyclin D1 transcriptional activity. RESULTS: CDX2 was expressed at a significantly higher level in QGP-1 cells than in KP-3 cells. Moreover, CDX2 was expressed at a middle level in 4 pancreatic ductal adenocarcinoma cells. Cell proliferation and cyclin D1 mRNA level were inhibited significantly after CDX2 transfection in pancreatic cancer cells. Furthermore, CDX2 inhibited exogenous nuclear factor kappaB-p65-induced luciferase gene expression in a dose-dependent manner. In addition, CDX2 inhibited pGL2HIVD1kappaB2-luciferase activity. CONCLUSIONS: CDX2 might play a role in inhibiting cell proliferation and repressing cyclin D1 transcriptional activity through the proximal nuclear factor kappaB binding site in pancreatic cancer cells.

Transnasal ultrathin endoscopy for placement of a long intestinal tube in patients with intestinal obstruction.

BACKGROUND: The technical difficulties related to the insertion of a long intestinal tube into the jejunum under fluoroscopy present a considerable problem in patients with an intestinal obstruction. OBJECTIVE: To evaluate the usefulness of endoscopic long intestinal-tube placement with the ultrathin esophagogastroduodenoscope (UT-EGD). DESIGN: A prospective randomized clinical trial was conducted. PATIENTS: Twenty-eight consecutive patients who presented with an intestinal obstruction were included in the study. INTERVENTION: The UT-EGD was inserted nasally into at least the second portion of the duodenum or beyond. After a guidewire was introduced through the working channel, with fluoroscopic guidance, the UT-EGD itself was carefully removed with the guidewire left in place. Next, a hydrophilic intestinal tube was advanced over the guidewire into the jejunum, and then the guidewire was removed. MAIN OUTCOME MEASUREMENTS: Primary end points are the total procedure time, the radiation exposure time, and the rate of complications, all compared with the conventional method. RESULTS: The mean (+/-SD) total procedure time was 18.7 +/- 8.4 minutes for the UT-EGD method and 39.5 +/- 15.0 minutes for the conventional method, with a significant time difference between the 2 methods (P < .0005). The mean (+/-SD) radiation exposure time was also shorter with the UT-EGD method (11.1 +/- 6.0 minutes) than with the conventional method (30.3 +/- 13.7 minutes) (P < .0005). There were no complications, except for mild nasal bleeding with each method. CONCLUSIONS: The UT-EGD method has definite advantages in the placement of a long intestinal tube for patients with an intestinal obstruction in comparison with the conventional method.

Autoimmune pancreatitis with retroperitoneal fibrosis which responded to steroid therapy but was complicated with refractory renal dysfunction.

A 58-year-old male had been diagnosed as having autoimmune pancreatitis (AIP) from the results of serological examinations and image findings. He was treated with prednisolone (PSL) for 3.5 months. Fifteen months later, follow-up CT revealed the main pancreatic duct (MPD) dilatation in the pancreas body to tail and right hydronephrosis caused by complicated retroperitoneal mass. We diagnosed him as having recurrent AIP with retroperitoneal fibrosis, and restarted PSL treatment. After one month, Examinations indicated amelioration of the MPD dilatation and right hydronephrosis, but not the right renal failure. This case indicates the importance of maintenance of PSL treatment.

A malignant nonfunctioning pancreatic endocrine tumor with a unique pattern of intraductal growth.

The intraductal growth of nonfunctioning pancreatic endocrine tumors (NFPTs) is considered to be rare, and in our survey of the English-language literature, we found only three cases to have been described previously. We herein report the case of a 36-year-old man with a malignant NFPT that uniquely grew within the lumen of the main pancreatic duct (MPD) and completely obstructed the MPD, as shown by endoscopic retrograde pancreatography (ERP). Endoscopic ultrasonography clearly detected the tumor with intraductal growth. In addition, positron emission tomography (PET), using 18F-fluorodeoxyglucose (FDG) and computed tomography (CT) with the same scanner (FDG-PET/CT) showed enhanced uptake of FDG in the tumor. A pylorus-preserving pancreaticoduodenectomy and regional lymphadenectomy were performed under the preoperative diagnosis of an NFPT. Microscopically, positive immunoreactions for synaptophisin and vasoactive intestinal peptide indicated neuroendocrine differentiation of the tumor, while in addition, metastasis to a lymph node along the common hepatic artery was also observed. The patient has survived for 6 months after the surgery without any evidence of recurrence or metastasis. Both ERP and FDG-PET/CT were thus found to be useful for predicting the malignant potential of an NFPT in the preoperative diagnosis.

Mucinous carcinoma of Vater's ampulla with a unique extension along the main pancreatic duct.

We report a case of mucinous carcinoma of Vater's ampulla with a unique extension along only the main pancreatic duct (MPD) and microinvasion to the pancreas. A 52-year-old man was referred to our hospital for the evaluation and treatment of acute pancreatitis. Abdominal computed tomography (CT) demonstrated swelling in the head of the pancreas with a mass in the duodenum. Hypotonic duodenography and endoscopic examination revealed a well-defined mass, measuring about 25 mm in size, in Vater's ampulla. A biopsy specimen of the tumor showed moderately differentiated adenocarcinoma. A pylorus-preserving pancreaticoduodenectomy with a regional lymphadenectomy was performed, under a preoperative diagnosis of adenocarcinoma of Vater's ampulla with direct invasion into the head of the pancreas. The resected specimen of the duodenum confirmed the presence of the mass, which measured 22 x 15 mm in size, in Vater's ampulla. Microscopically, the tumor consisted of two components: moderately differentiated adenocarcinoma in the peripheral region of the tumor Vater's papilla and mucinous carcinoma in the central region of the tumor. The mucinous carcinoma component uniquely extended along only the MPD with microinvasion to the pancreas. Immunohistochemically, both the moderately differentiated adenocarcinoma and the mucinous carcinoma were positive for cytokeratin 20 (CK20) and negative for cytokeratin 7 (CK7) which is the pattern of intestinal-type carcinoma of Vater's ampulla. We concluded that the original site of this tumor may have been the duodenal epithelium of Vater's ampulla originally moderately differentiated adenocarcinoma-which subsequently changed to mucinous carcinoma that extended along only the MPD with microinvasion to the pancreas.

Endoscopic diagnosis and staging of mucinous cystic neoplasms and intraductal papillary-mucinous tumors.

BACKGROUND/PURPOSE: The number of patients with cystic neoplasms of the pancreas as detected using various types of imaging techniques has been steadily increasing. Among the cystic neoplasms, mucinous cystic neoplasms (MCNs) and intraductal papillary-mucinous tumors (IPMTs) were comparatively more frequently encountered. We used imaging techniques to focus on the differential diagnosis of MCNs and IPMTs, and tumor staging. METHODS: Fifteen patients with MCNs with ovarian-like stroma and 109 patients with IPMTs were experienced. We examined the image findings for the differential diagnosis and stage diagnosis of these two types of cystic neoplasms. RESULTS: Endoscopic ultrasonography could reveal detailed images of internal structure and was effective for the diagnosis of MCNs. Other endoscopic imaging modalities could not give specific findings for MCNs. Endoscopic retrograde cholangiopancreatography (ERCP; including duodenoscopic findings and pancreatogram) and pancreatoscopy showed the characteristic and specific findings of IPMTs. Also, endoscopic ultrasonography and intraductal ultrasonography were found to have high sensitivity and diagnostic accuracy for their differential diagnosis of neoplastic/nonneoplastic and invasive/noninvasive lesions in IPMTs. CONCLUSIONS: Endoscopic imaging techniques are capable of revealing the detailed structure of pancreatic cystic lesions. They are effective for differential diagnosis, for assessing the degree of malignancy, and for deciding upon an appropriate treatment in patients with IPMTs.

Efficacy of peroral pancreatoscopy in the diagnosis of pancreatic diseases.

BACKGROUND: The aim of this study was to evaluate the usefulness of peroral pancreatoscopy in the diagnosis of pancreatic diseases. METHODS: Both 3.7-mm (thin) and 0.8-mm (ultra-thin) diameter fiberoptic pancreatoscopes were used in 115 cases (pancreatic cancer, 35; benign ductal stenosis, 20; intraductal papillary-mucinous tumor, 60). RESULTS: Observation rates for pancreatic cancer, benign ductal stenosis, and intraductal papillary-mucinous tumor were, respectively, 63%, 80%, and 95%. Tumor vessels and papillary tumor were observed when pancreatic cancer was smaller than 2 cm but not when the tumor was larger than 2 cm. Stenosis without significant mucosal changes was observed in 62% of cases of benign ductal stenosis. Coarse mucosa and friability were observed more frequently in association with pancreatic cancer than benign ductal stenosis. Granular mucosa or papillary tumor could be observed in 74% of cases of intraductal papillary-mucinous tumor. Papillary tumor was observed with increasing frequency in cases of intraductal papillary-mucinous tumor as the degree of malignancy increased. CONCLUSIONS: Peroral pancreatoscopy with an ultra-thin fiberscope is useful in the diagnosis of minute pancreatic lesions. Peroral pancreatoscopy with a thin fiberscope can provide a definitive diagnosis of intraductal papillary-mucinous tumor including the degree of malignancy.

A two-step method for marking polypectomy sites in the colon and rectum.

BACKGROUND: Intraoperative localization of polypectomy sites is critical for laparoscopic and open surgery, but conventional methods of marking the colorectum are sometimes unreliable. A new two-step method for marking polypectomy sites for identification during laparoscopic and open operations is described. METHODS: Eighteen patients with postpolypectomy lesions necessitating preoperative marking were enrolled in this study. A physiologic saline solution was endoscopically injected into the submucosa to produce an artificial submucosal elevation (pseudopolyp). A small volume of India ink was then injected into the submucosal elevation (pseudopolyp) with a separate needle. RESULTS: The two-step method was easily applied for all lesions without complication. At surgery, all lesions were immediately visualized. CONCLUSION: The two-step tattooing method proved to be easy, safe, and accurate for marking polypectomy sites.