Modeling Drug-Induced Neuropathy Using Human iPSCs for Predictive Toxicology.

Drugs under development can cause unpredicted toxicity in humans due to differential drug responsiveness between humans and other disease models, resulting in clinical trial failures. Human induced pluripotent stem cells (iPSCs) are expected to represent a useful tool for toxicity testing. However, among many assays, appropriate cellular assays for predicting neurotoxicity in an iPSC-based model are still uncertain. Here we generated neurons from iPSCs of Charcot-Marie-Tooth disease (CMT) patients. Some CMT patients are sensitive to anticancer drugs and present with an adverse reaction of neuropathy. We analyzed cellular phenotypes and found that mitochondria in neurites of CMT neurons were morphologically shorter and showed slower mobility compared to control. A neurosphere assay showed that treatment with drugs known to cause neuropathy caused mitochondrial aggregations in neurites with adenosine triphosphate shortage in both CMT and control neurons, although more severely in CMT. These findings suggest that the genetically susceptible model could provide a useful tool to predict drug-induced neurotoxicity.

Randomised phase II trial of S-1 plus oxaliplatin vs S-1 in patients with gemcitabine-refractory pancreatic cancer.

BACKGROUND: This randomised, open-label, multicenter phase II study compared progression-free survival (PFS) of S-1 plus oxaliplatin (SOX) with that of S-1 alone in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients with confirmed progressive disease following the first-line treatment with a gemcitabine-based regimen were randomised to receive either S-1 (80/100/120 mg day(-1) based on body surface area (BSA), orally, days 1-28, every 6 weeks) or SOX (S-1 80/100/120 mg day(-1) based on BSA, orally, days 1-14, plus oxaliplatin 100 mg m(-2), intravenously, day 1, every 3 weeks). The primary end point was PFS. RESULTS: Between January 2009 and July 2010, 271 patients were randomly allocated to either S-1 (n=135) or SOX (n=136). Median PFS for S-1 and SOX were 2.8 and 3.0 months, respectively (hazard ratio (HR)=0.84; 95% confidence interval (CI), 0.65-1.08; stratified log-rank test P=0.18). Median overall survival (OS) was 6.9 vs 7.4 months (HR=1.03; 95% CI, 0.79-1.34; stratified log-rank test P=0.82). The response rate (RR) was 11.5% vs 20.9% (P=0.04). The major grade 3/4 toxicities (S-1 and SOX) were neutropenia (11.4% and 8.1%), thrombocytopenia (4.5% and 10.3%) and anorexia (12.9% and 14.7%). CONCLUSIONS: Although SOX showed an advantage in RR, it provided no significant improvement in PFS or OS compared with S-1 alone.

Enhanced specificity of HPV16 E6E7 siRNA by RNA-DNA chimera modification.

Although efforts have been made to develop new drugs for infectious and neoplastic diseases utilizing synthetic small interfering RNA(siRNAs), those intrinsically have undesirable effects, including silencing of unintended genes (off-target effect) and nonspecific cytotoxicity. Off-target effects can be avoided by DNA substitution in the guide strand (GS) seed region of nucleotide positions 1-8 and its complementary part of the passenger strand plus the 3' overhang, which is designated as a double-strand RNA-DNA chimera (dsRDC). In this study, we found that the specificity of potent siRNAs targeting human papillomavirus 16 (HPV16) E6 and E7 oncogenes, which we previously reported, could be enhanced by short dsRDC modification (first six nucleotides from the 5' end of the GS and its complementary nucleotides of the passenger strand). Such dsRDC modification reduced nonspecific cytotoxicity in two of three siRNAs (497 and 752), although not in the other (573), which correlated with their off-target effects. In addition, silencing activity was marginally impaired in two dsRDCs (497 and 573) and moderately in one (752). Finally, dsRDC-497 induced E6E7-specific growth suppression of cervical cancer cells as well as E6E7-immortalized human keratinocytes. Our results show that dsRDC modification enhances the specificity of E6E7 siRNA, which is required for use in in vivo settings.

Can MRCP replace ERCP for the diagnosis of autoimmune pancreatitis?

BACKGROUND: It is of utmost importance that autoimmune pancreatitis (AIP) be differentiated from pancreatic cancer. Irregular narrowing of the main pancreatic duct is a characteristic finding in AIP; it is useful for differentiating AIP from pancreatic cancer stenosis. This study evaluated the usefulness of magnetic resonance cholangiopancreatography (MRCP) for the diagnosis of AIP and assessed whether MRCP could replace endoscopic retrograde cholangiopancreatography (ERCP) for diagnosing AIP. METHODS: The MRCP and ERCP findings of 20 AIP patients were compared. RESULTS: On MRCP, the narrowed portion of the main pancreatic duct was not visualized, while the noninvolved segments of the pancreatic duct were visualized. The degree of upstream dilatation of the proximal main pancreatic duct was milder in AIP than in pancreatic cancer patients. In the skipped type, only skipped narrowed lesions were not visualized. After steroid therapy for AIP, the nonvisualized main pancreatic duct became visualized. CONCLUSIONS: MRCP cannot replace ERCP for the diagnosis of AIP, since narrowing of the main pancreatic duct in AIP was not visualized on MRCP. MRCP findings of segmental or skipped nonvisualized main pancreatic duct accompanied by a less dilated upstream main pancreatic duct may suggest the presence of AIP. MRCP is useful for following AIP patients.

Characterization of carotid atherosclerosis and detection of soft plaque with use of black-blood MR imaging.

BACKGROUND AND PURPOSE: In the treatment of carotid atherosclerosis, the rate of stenosis and characteristics of plaque should be assessed to diagnose vulnerable plaques that increase the risk for cerebral infarction. We performed carotid black-blood (BB) MR imaging to diagnose plaque components and assess plaque hardness based on MR signals. MATERIALS AND METHODS: Three images of BB-MR imaging per plaque were obtained from 70 consecutive patients who underwent carotid endarterectomy (CEA) to generate T1- and T2-weighted images. To evaluate the relative signal intensity (rSI) of plaque components and the relationship between histologic findings and symptoms, we prepared sections at 2-mm intervals from 34 intact plaques. We then calculated the relative overall signal intensity (roSI) of 70 plaques to assess the relationship between MR signal intensity and plaque hardness and symptoms. RESULTS: The characteristics of rSI values on T1- and T2-weighted images of fibrous cap (FC), fibrosis, calcification, myxomatous tissue, lipid core (LC) with intraplaque hemorrhage (IPH), and LC without IPH differed. Symptomatic plaques were associated with FC disruption (P < .001) and LC with IPH (P < .05). The roSI on T1-weighted images was significantly higher for soft than nonsoft plaques. When the roSI cutoff value was set at 1.25 (mean of the roSI), soft plaques were diagnosed with 79.4% sensitivity and 84.4% specificity. The roSI was also significantly higher for symptomatic than for asymptomatic plaques. Soft and nonsoft plaques as well as symptomatic and asymptomatic plaques did not significantly differ on T2-weighted images. CONCLUSION: BB-MR imaging can diagnose plaque components and predict plaque hardness. This procedure provides useful information for planning therapeutic strategies of carotid atherosclerosis.

Pancreatographic investigation of the pancreatic duct system.

BACKGROUND: Embryologically, the pancreatic duct system develops by the fusion between the dorsal and ventral pancreatic bud ducts. It has been suggested that the proximal part of the main dorsal pancreatic duct partially regresses to form the accessory pancreatic duct (APD). Aim of this study was to clarify the anatomy of the pancreatic duct system of the head of the pancreas and investigate the embryology of the normal pancreatic duct system. METHODS: We reviewed endoscopic retrograde pancreatography of normal pancreatic heads (n = 256) and pancreas divisum (n = 36), focusing on long inferior branches arising from the APD and the main pancreatic duct (MPD). The accessory pancreatograms were divided into two patterns of course and shape, the long type (171 cases) and the short type (85 cases) according to the length of the MPD from the orifice to the junction with the APD. The long-type APD formed a straight line and joined the MPD at the neck portion of the pancreas. The short-type APD joined the MPD near its first inferior branch. RESULTS: The shape of the long-type APD was quite similar to that of the dorsal pancreatic duct of pancreas divisum. The short-type APD was less likely to have a long inferior branch arising from the APD. The length of the APD from the orifice to the first long inferior branch was similar in the long-type APD (19.4 +/- 4.0 mm) and in the short-type APD (18.8 +/- 4.2 mm). The first long inferior branch from the long-type APD passed though the MPD near the origin of the inferior branch from the MPD, whereas the short-type APD joined the MPD near its inferior branch. CONCLUSIONS: There are two types of APD. The long-type APD was quite similar to the shape of the dorsal pancreatic duct of pancreas divisum, and seems to represent a continuation of the main duct of the dorsal pancreatic bud. The short-type APD was less likely to have a long inferior branch, and seems to be formed by the most proximal part of the main duct of the dorsal pancreatic bud and its long inferior branch.

MRCP of congenital pancreaticobiliary malformation.

BACKGROUND: Congenital pancreaticobiliary malformations are sometimes associated with acute or chronic pancreatitis and biliary carcinoma. Currently, magnetic resonance cholangiopancreatography (MRCP) is one of the first choices for investigating and diagnosing pancreaticobiliary diseases noninvasively. We compared the accuracy of conventional MRCP and endoscopic retrograde cholangiopancreatography (ERCP) in making the diagnosis of congenital pancreaticobiliary malformations. METHODS: In patients with pancreas divisum (n = 17), pancreaticobiliary maljunction (n = 12), choledochocele (n = 2), and annular pancreas (n = 1) who underwent ERCP and MRCP, the diagnostic accuracy and findings on MRCP were compared with those on ERCP. RESULTS: Of the 32 patients with congenital pancreaticobiliary malformations diagnosed on ERCP, 23 (72%) presented the same diagnosis on MRCP. Complete pancreas divisum was diagnosed in 73% on MRCP based on the finding of a dominant dorsal pancreatic duct crossing the lower bile duct and emptying into the duodenum without communicating with the ventral pancreatic duct. Pancreaticobiliary maljunction was diagnosed in 75% on MRCP based on the finding of an anomalous union between the common bile duct and the pancreatic duct and the existence of a long common channel. CONCLUSIONS: Conventional MRCP is a useful, noninvasive tool for diagnosing congenital pancreaticobiliary malformations; and the diagnostic accuracy can be increased with three-dimensional MRCP or dynamic MRCP with secretin stimulation.

The presence of a common channel and associated pancreaticobiliary diseases: a prospective ERCP study.

BACKGROUND: There are few endoscopic retrograde cholangiographic studies dealing with the relationship between the presence of a common channel and associated pancreaticobiliary diseases. AIMS: To endoscopically determine the incidence of common channels and assess whether the anatomy of the pancreaticobiliary ductal drainage into the duodenum has any bearing on pancreaticobiliary diseases. PATIENTS AND METHODS: We prospectively examined a common channel formation in 354 endoscopic retrograde cholangiographic cases. Cases with a common channel were divided into three groups: pancreaticobiliary maljunction, high confluence of pancreaticobiliary ducts with a common channel > or =6 mm in which the communication was occluded with the sphincter contraction, and common channel < or =5 mm in length. RESULTS: A common channel was observed in 131 cases (37.0%) including 11 with pancreaticobiliary maljunction and 13 with high confluence of pancreaticobiliary ducts. In cases with a common channel, the incidences of associated gallbladder carcinoma and acute pancreatitis were both 11.5%, which were significantly higher than 1.8% and 4.9% seen in cases without a common channel. In pancreaticobiliary maljunction cases, incidence of associated gallbladder carcinoma was 72.7%. CONCLUSION: The presence of an obvious common channel was observed in 37.0%. A close relationship is suggested between the presence of a common channel and development of gallbladder carcinoma and acute pancreatitis.

Gastrointestinal findings in patients with autoimmune pancreatitis.

BACKGROUND AND STUDY AIMS: Autoimmune pancreatitis (AIP) is a condition that has been proposed as a clinical entity only fairly recently. Its pathogenesis involves autoimmune mechanisms. Although the radiological findings in patients with AIP have been well evaluated, few studies have focused on the gastrointestinal findings in these patients. The aim of this study was to explore the endoscopic and histological findings in the gastrointestinal tract in patients with autoimmune pancreatitis. PATIENTS AND METHODS: The endoscopic findings in the stomach (n = 10), the duodenum (n = 18), the major duodenal papilla (n = 18), and the colon (n = 5) in 24 patients with AIP were reviewed. These were compared with the results of histological examination of gastric mucosa (n = 13), duodenal mucosa (n = 9), the major duodenal papilla (n = 3), and colonic mucosa (n = 3) in these patients. All these specimens were subjected to immunohistochemical study using anti-IgG4 antibody. RESULTS: Foci of slightly pale, thickened mucosa with loss of visible vascular pattern were observed in the stomach in four patients and in the colon in two patients on endoscopy. Slight or moderate swelling of the major duodenal papilla was detected in five patients. Slight to moderate lymphoplasmacytic infiltration was observed in the lamina propria of the gastric and colonic mucosa, and of the major duodenal papilla. Heavy infiltration with IgG4-positive plasma cells (>10 cells per high-power field) was observed in the lamina propria of the stomach in seven patients, of the colon in two patients, and of the major duodenal papilla in three patients; this was not observed in the control patients, who had other diseases. CONCLUSIONS: Although there were no specific endoscopic findings in the stomach or colon in patients with autoimmune pancreatitis, foci of slightly pale, thickened mucosa with loss of visible vascular pattern were observed in some cases. This indistinct change seen on endoscopy appears to be due to heavy infiltration with IgG4-positive plasma cells, associated with CD4- or CD8-positive T lymphocytes, in the lamina propria of the gastric or colonic mucosa.

Human papillomavirus-associated plantar epidermoid cyst related to epidermoid metaplasia of the eccrine duct epithelium: a combined histological, immunohistochemical, DNA-DNA in situ hybridization and three-dimensional reconstruction analysis.

BACKGROUND: We recently proposed that certain palmoplantar epidermoid cysts may be related to eccrine ducts and that human papillomavirus (HPV) 60 may play a role in their pathomechanism. However, the origin of palmoplantar epidermoid cysts is still controversial. OBJECTIVES: To examine the contribution of eccrine ducts and HPV 60 in the development of epidermoid cysts. METHODS: Five epidermoid cysts and four ridged warts that had developed on the soles of a patient were studied histologically, immunohistochemically and by DNA-DNA in situ hybridization. Using serial sections obtained from its entire body, a three-dimensional reconstruction (3DR) analysis was performed on the smallest cyst to analyse the relationship between the epidermoid cyst, eccrine duct and the overlying epidermis. RESULTS: Histological and DNA-DNA in situ hybridization analyses demonstrated both homogeneous intracytoplasmic inclusion bodies pathognomonic for HPV 60 infection and HPV 60 DNA sequences not only in all of the epidermoid cysts and ridged warts but also in the acrosyringeal portion of an eccrine duct, with the dermal portion of which the smallest cyst had been revealed to connect by 3DR analysis. However, immunohistochemical analyses using antibodies against human carcinoembryonic antigen (CEA), involucrin and several cytokeratins (CKs) revealed that the immunoreactivity of the cyst was not identical to that of the eccrine dermal duct but was identical to that of suprabasal layers of the epidermis. CONCLUSIONS: It was clearly demonstrated that an HPV 60-associated epidermoid cyst with immunoreactivities for CEA, involucrin and CKs which were identical to those of the epidermis connected with the eccrine dermal duct, supporting the idea that certain palmoplantar epidermoid cysts may develop following the epidermoid metaplasia of eccrine ducts with HPV 60 infection.

Clinical features and treatment of hematopoietic stem cell transplantation-associated gastric antral vascular ectasia.

Gastric antral vascular ectasia (GAVE) may occur after hematopoietic stem cell transplantation (HSCT) and cause severe and prolonged gastric bleeding. The underlying pathology of transplant-associated GAVE (HSCT-GAVE) is poorly understood and an effective therapeutic strategy has not been established yet. We retrospectively reviewed the medical records of 230 consecutive allogeneic transplant recipients in our institution between January 1997 and June 2002. We identified five patients who developed HSCT-GAVE (2.2%). Four patients had bleeding from HSCT-GAVE and one patient had HSCT-GAVE discovered incidentally. The clinical features of these patients were similar in that they all received conditioning treatment with busulfan and had history of thrombotic microangiopathy. Furthermore, treatment with a beta-blocker apparently improved the outcome of HSCT-GAVE in three patients.

Ten-year prospective follow-up study on the relationship between Helicobacter pylori infection and progression of atrophic gastritis, particularly assessed by endoscopic findings.

AIM: To ascertain the progression of atrophic gastritis due to Helicobacter pylori infection, we conducted a 10-year prospective follow-up study with annual endoscopy of the stomach. METHODS: Prospective endoscopic observation was started in 53 subjects in 1989 and 1990 after informed consent was obtained. The progression of atrophic gastritis was evaluated mainly by the endoscopic pattern of atrophy. Histological assessment was performed on biopsy specimens taken from the lesser curvature of the lower corpus. By 2000, 43 patients (20 males, 23 females, mean age 56.7 years at entry) had completed at least 10 years of endoscopic follow-up. RESULTS: Eight H. pylori-negative patients with normal fundic mucosa showed no change endoscopically or histologically. In 35 H. pylori-positive patients, the progression of histological atrophy was observed in 46% and intestinal metaplasia was observed in 49%. Fifteen of 35 H. pylori-positive cases exhibited a cephaloid shift of the endoscopic atrophic border. The cephaloid shift of the atrophic area occured suddenly. The cumulative progression rate of atrophic patterns was 6% after 2 years, 22% after 4 years, 34% after 6 years and 43% after 10 years. These atrophic changes were related to neutrophil infiltration. CONCLUSION: The progression of atrophic gastritis is a result of chronic active gastritis caused by H. pylori infection.

Survival benefits of adjuvant chemotherapy with oral doxifluridine (5'-DFUR) following radiotherapy in patients with unresectable pancreatic cancer.

BACKGROUND AND OBJECTIVES: The combination of 5-fluorouracil and radiotherapy is thought to be the most effective treatment for locally unresectable pancreatic carcinoma. The outcomes, however, are far from acceptable from the viewpoint of long-term survival. We assessed the survival benefits of oral adjuvant chemotherapy with doxifluridine (5'-DFUR) following radiotherapy for patients with the disease. METHODS: Thirty-five consecutive patients who underwent bypass surgery and radiotherapy for localized advanced unresectable adenocarcinoma of the pancreas head were retrospectively reviewed in regard to disease progression and survival. Ten of the 35 patients underwent adjuvant chemotherapy with 5'-DFUR after radiotherapy in an outpatient setting. RESULTS: The 1-year survival for patients treated with radiotherapy alone was 29%. The 1-, 2-, and 3-year survivals for patients treated with the adjuvant chemotherapy after radiotherapy were 50, 40, and 30%, respectively (P = 0.0069, log-rank test). The elevation of tumor markers was delayed (P = 0.0346) and local control rate was improved (P = 0.0475) in patients with chemotherapy. Multivariate analysis demonstrated that the adjuvant chemotherapy with 5'-DFUR was a significant independent prognostic factor as well as tumor size. CONCLUSIONS: The adjuvant chemotherapy with 5'-DFUR following radiotherapy led to a significant prolongation of the survival for patients with unresectable localized pancreatic cancer.

Adenovirus-mediated transfer of p53 augments hyperthermia-induced apoptosis in U251 glioma cells.

PURPOSE: Hyperthermia kills glioma cells by inducing apoptosis and is thereby an effective therapeutic modality for the treatment of malignant gliomas. However, cells harboring mutated p53 are refractory to hyperthermia-induced apoptosis. In this study, we assessed whether or not adenovirus (Adv)-mediated transduction of p53 overrides this resistant mechanism. METHODS AND MATERIALS: We transduced the p53 wild-type tumor suppressor gene into U251 glioma cells harboring mutated p53 using Adv vectors in combination with hyperthermia (43, 44.5 degrees C), and evaluated the degree of cell death and apoptosis. RESULTS: The percentage of cells that had died, as measured by trypan blue staining, among U251 cells infected with the Adv for p53 (Adv-p53) and treated with hyperthermia, was significantly higher than the percentage of cells that had died among U251 cells infected with Adv-p53 and not treated with hyperthermia, or those infected with the control Adv for dE (Adv-dE) and treated with hyperthermia. The degree of apoptosis, measured at 24 h after treatment, in hyperthermia-treated U251 cells infected with Adv-p53 (43 degrees C, 73%; 44.5 degrees C, 92%) was much higher than that infected with Adv-p53 (41%), or that infected with control Adv-dE and treated with hyperthermia (43 degrees C, 1.3%; 44.5 degrees C, 19%). Treatment with combined hyperthermia and Adv-p53 infection induced cleavage of caspase-3 in U251 cells. CONCLUSION: These results indicate that Adv-mediated transduction of p53 would render glioma cells highly sensitive to hyperthermia.

[Clinicopathologic study on chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct].

We studied the clinicopathologic features of 13 cases of chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct (MPD). It occurs frequently in relatively elder men. Diffuse irregular narrowing of the MPD and stenosis of the common bile duct on ERCP, and swelling of the pancreas on US/CT were detected in all cases. An autoimmune mechanism might be involved in the etiology at least in 5 patients with hypergammaglobulinemia and positive autoantibodies. Surgical therapy was performed in 8 patients and 3 patients were treated with steroids. No patients showed recurrence of pancreatitis. Histologic findings were characterized by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis in the pancreas, obliterated phlebitis of the pancreatic veins. Similar inflammatory process involved the bile duct and the gallbladder. These histologic findings were similar to those of multifocal fibrosclerosis. Chronic pancreatitis with diffuse irregular narrowing of the MPD is overlapped with autoimmune pancreatitis in many cases, but may be a variant of multifocal fibrosclerosis involving the pancreas in some cases.

Primary sclerosing cholangitis complicated with idiopathic thrombocytopenic purpura.

We present a 66-year-old woman with primary sclerosing cholangitis (PSC) complicated with idiopathic thrombocytopenic purpura (ITP). Both PSC and ITP are considered to reflect an immunological disturbance. However, their coexistence is very rare and to the best of our knowledge this is only the second reported case. In Japan, PSC patients are rarely treated with liver transplantation. Fortunately, the present patient underwent successful hepatic transplantation from a brain-dead donor and simultaneous splenectomy. This case emphasizes the importance of liver transplantation as an effective treatment for primary sclerosing cholangitis.

Immunohistochemical localization of pancreatic secretory trypsin inhibitor in malignant pancreatic endocrine tumors.

Differentiation of benign from malignant pancreatic endocrine tumors by existing clinical, biochemical, histologic, and cytologic criteria is difficult. We immunohistochemically localized pancreatic secretory trypsin inhibitor (PSTI) in 28 pancreatic endocrine tumors (13 benign, 15 malignant). PSTI-immunoreactive cells were detected in nine endocrine tumors. Immunoreactivity in these tumors was detected in nearly all tumor cells in five cases, scattered cells in two cases, and a few cells in two cases. All positive cases were malignant, and eight were equal to or larger than 10 cm. Serum concentrations of PSTI were markedly elevated in the two patients so tested. PSTI may be a specific immunohistochemical marker for malignant pancreatic endocrine tumors.

Possibility of slow-growing variants in pancreatic adenocarcinoma.

Four patients with advanced pancreatic adenocarcinoma suggesting slow-growing tumors are reported on. Tumors in 2 of the 4 were far-advanced, but both survived for over 3 years after treatment. One demonstrated 165 days of serum CA 19-9 level doubling time (T2CA 19-9), while the other demonstrated 135 days of DUPAN II level doubling time. Late tumor recurrence was observed in the remaining 2 patients who survived over 8 years after surgery, demonstrating long-term T2CA 19-9. A long-term T2CA 19-9 of 141 days was correlated with slow tumor growth in computed tomography (CT) scans in 1 patient, who survived 2.5 years after evidence of recurrent tumor without supplementary therapy. These observations, which suggest slow-growing variants, have not been reported in the literature on pancreatic adenocarcinoma. A significant difference was also seen in tumor-marker doubling time among 6 patients who survived over 3 years and 26 patients who did not (p = 0.02). Thus, the doubling time may characterize certain tumors biologically in a way that is useful in practice for predicting disease outcome.

Patency of the accessory pancreatic duct in relation to its course and shape: a dye-injection endoscopic retrograde pancreatography study.

OBJECTIVE: The accessory pancreatic duct (APD) exhibits several appearances on pancreatography. We examined the patency of the APD by dye-injection endoscopic retrograde pancreatography (ERP), and studied the relationship between patency and duct course and shape. METHODS: There were 213 patients with satisfactory imaging of the entire normal APD who also underwent dye-injection ERP. The length and maximum diameter of the APD and the length of the main pancreatic duct (MPD) from its orifice to the junction with the APD were measured. RESULTS: The caliber of the patent APD was 1.6 +/- 0.6 mm. This was significantly larger than the caliber (1.1 +/- 0.4 mm) of the nonpatent APD (p < 0.01). The length of the MPD from its orifice to the junction with the patent APD was 32.7 +/- 12.5 mm. This was significantly longer than the length to the junction with the nonpatent APD (22.5 +/- 8.1 mm) (p < 0.01). The APD was classified according to duct course: long type, intermediate type, short type, or ansa type. Patency was most common in the long type APD (74.5%). The terminal shape of the APD was also used to classify the ducts: stick type, branch type, saccular type, cudgel type, or spindle type. Patency was most frequently observed in the spindle and cudgel type ducts. CONCLUSIONS: Patency of the APD might be dependent on duct caliber, course, and terminal shape of the duct.