Gateway reflexes describe novel neuro-immune communications that establish immune cell gateways at specific vessels.

Neuroinflammation is an important biological process induced by complex interactions between immune cells and neuronal cells in the central nervous system (CNS). Recent research on the bidirectional communication between neuronal and immunological systems has provided evidence for how immune and inflammatory processes are regulated by nerve activation. One example is the gateway reflex, in which immune cells bypass the blood brain barrier and infiltrate the CNS to cause neuroinflammation. We have found several modes of the gateway reflex in mouse models, in which gateways for immune cells are established at specific blood vessels in the spinal cords and brain in experimental autoimmune encephalomyelitis and systemic lupus erythematosus models, at retinal blood vessels in an experimental autoimmune uveitis model, and the ankle joints in an inflammatory arthritis model. Several environmental stimulations, including physical and psychological stresses, activate neurological pathways that alter immunological responses via the gateway reflex, thus contributing to the development/suppression of autoimmune diseases. In the manuscript, we describe the discovery of the gateway reflex and recent insights on how they regulate disease development. We hypothesize that artificial manipulation of specific neural pathways can establish and/or close the gateways to control the development of autoimmune diseases.

An inflammatory bowel disease-associated SNP increases local thyroglobulin expression to develop inflammation in miniature dachshunds.

Inflammatory colorectal polyp (ICRP) in miniature dachshunds (MDs) is a chronic inflammatory bowel disease (IBD) characterized by granulomatous inflammation that consists of neutrophil infiltration and goblet cell hyperplasia in the colon. Recently, we identified five MD-associated single-nucleotide polymorphisms (SNPs), namely PLG, TCOF1, TG, COL9A2, and COL4A4, by whole-exome sequencing. Here, we investigated whether TG c.4567C>T (p.R1523W) is associated with the ICRP pathology. We found that the frequency of the T/T SNP risk allele was significantly increased in MDs with ICRP. In vitro experiments showed that TG expression in non-immune cells was increased by inducing the IL-6 amplifier with IL-6 and TNF-α. On the other hand, a deficiency of TG suppressed the IL-6 amplifier. Moreover, recombinant TG treatment enhanced the activation of the IL-6 amplifier, suggesting that TG is both a positive regulator and a target of the IL-6 amplifier. We also found that TG expression together with two NF-κB targets, IL6 and CCL2, was increased in colon samples isolated from MDs with the T/T risk allele compared to those with the C/C non-risk allele, but serum TG was not increased. Cumulatively, these results suggest that the T/T SNP is an expression quantitative trait locus (eQTL) of TG mRNA in the colon, and local TG expression triggered by this SNP increases the risk of ICRP in MDs via the IL-6 amplifier. Therefore, TG c.4567C>T is a diagnostic target for ICRP in MDs, and TG-mediated IL-6 amplifier activation in the colon is a possible therapeutic target for ICRP.

Efficacy and safety of a WallFlex enteral stent for malignant gastric obstruction.

AIM: The aim of the present study was to investigate the efficacy and safety of a newly available enteral WallFlex stent for malignant gastric outlet obstruction (GOO). METHODS: Twenty-one consecutive patients with symptomatic (unable to take solids) malignant GOO treated by a WallFlex stent from April 2010 to February 2012 were included and analyzed retrospectively. Main outcome measurements were technical success, early complications, clinical response (elimination of the need for nasogastric tube drainage), clinical success (improvement of oral intake to a GOO score of 2 or 3), and duration of sustaining a GOO score of 2 or 3 after clinical success (median duration until reworsening of GOO score to <2 by the Kaplan-Meier method). A four-point GOO scoring system (0-3) was used for estimation of oral intake. RESULTS: Technical success rate was 100%. Bleeding and perforation after stent placement and stent dislocation/migration in the follow-up period did not occur in any patients, whereas one patient (5%) developed moderate post-procedural pancreatitis. Clinical response and clinical success was achieved in all patients and in 81% (17/21), respectively. In 17 patients whose GOO score had improved to 2 or 3 after stent placement, eight (47%) developed reworsening of the GOO score to <2 with a median time of 148 days (95% confidence interval [CI], 0-328; Kaplan-Meier method). Median survival time after the initial intervention was 61 days (95% CI, 40-82). CONCLUSION: Placement of an enteral WallFlex stent in patients with malignant GOO is safe and effective.

Clinicopathological study on endocrine cell micronests associated with early gastric cancer.

OBJECTIVE: The purpose of this study was to review cases of early gastric cancer associated with Endocrine cell micronests (ECM) and investigate the incidence and characteristics of these lesions. METHODS: A total of 482 patients who had undergone endoscopic or surgical resection for gastric epithelial neoplasms from April 2008 to March 2010 were enrolled in this study. After detection of ECM in the lamina propria mucosa by histological examination of the resected specimens with hematoxilin-eosin staining, immunostaining was also performed. Clinical manifestation and endoscopic findings, as well as histological findings, were examined. RESULTS: Among the 482 patients, 5 (1.0%) had ECM. The histological type of gastric epithelial cancers associated with ECM was tubular adenocarcinoma and carcinoma in situ (Tis) in the WHO classification in all 5 cases. ECM were round to oval or trabecular and located within the area of the early gastric cancer in all the 5 cases. The background gastric mucosa was Type A gastritis in 2 patients and ordinary atrophic gastritis in 2 patients. In the other case, it was difficult to determine the type of gastritis. CONCLUSION: ECM developed not only from the background of Type A gastritis but also from ordinary atrophic gastritis. ECM coexistent with gastric cancer were present in 1.0% of resectable gastric epithelial neoplasms.

A case of mucosal cancer of the stomach treated by endoscopic submucosal dissection after which nodal metastasis became evident.

An 82-year-old male was referred to our institution for evaluation and treatment of a protruding lesion in the stomach. Esophagogastroduodenoscopy (EGD) showed a small protruding lesion and a large superficial elevated lesion on the lesser curvature of the stomach (macroscopic type: 0-I and 0-IIa, resp.). CT and endoscopic ultrasonography (EUS) visualized a small round lymph node (LN) 11 mm in size near the lesser curvature, although submucosal invasion was not evident. These two lesions were resected en bloc by endoscopic submucosal dissection (ESD). Pathological examination of the resected specimen showed moderately differentiated tubular adenocarcinoma (tub2) and well-differentiated tubular adenocarcinoma (tub1), respectively, which were limited to the mucosal layer. Because lymphatic-vascular involvement was not detected by hematoxylin and eosin (HE) staining, additional gastrectomy was not performed. Two months after ESD, follow-up EUS and CT showed an enlarged LN. EUS-guided fine needle aspiration (EUS-FNA) for the LN revealed metastasis. Therefore, total gastrectomy with LN dissection was performed. His postoperative course was uneventful. After discharge, he has been followed up at the outpatient department without any sign of recurrence for 5 years. Histological reexamination of the ESD specimen using immunohistochemistry showed lymphatic invasion of cancer cells in the lamina propria of the 0-I lesion 13 mm in size.

Prospective evaluation of contrast-enhanced computed tomography for the detection of colonic diverticular bleeding.

BACKGROUND AND AIMS: To prospectively evaluate the role of contrast-enhanced computed tomography (CE-CT) in the detection of colonic diverticular bleeding (CDB). PATIENTS AND METHODS: Consecutive patients who presented with hematochezia and were clinically suspected of CDB were prospectively enrolled. Those who could undergo both CE-CT and total colonoscopy, and who were finally diagnosed as CDB, were included in the analysis. RESULTS: Fifty-two cases were finally included in the analysis. The detection rate of CDB by CT was 15.4 % (8/52). Univariate analysis showed that the interval from the latest episode of hematochezia to the performance of CT and the presence of a past history of CDB were contributing factors for detection. The interval was 1.6 ± 4.6 h (mean ± SD) in patients detected by CT, and 3.4 ± 3.2 h in those without detection. The detection rate of CDB by total colonoscopy was 38.5 % (20/52). The overall detection rate was 46.2 % (24/52), which was superior to what CT or colonoscopy alone achieved. CONCLUSIONS: CE-CT may play a complementary role to colonoscopy in patients with suspected CDB, but is not recommended for all cases due to its low detection rate. Patients who can be examined within 2 h of last hematochezia would be candidates for urgent CT.

Efficacy of acetic acid-spraying method in diagnosing extension of Barrett's cancer under the squamous epithelium.

AIM: Endoscopic diagnosis of the lateral extension of Barrett's cancer under the squamous epithelium (BCUS) is sometimes difficult because the cancer is unobservable in the esophageal lumen. The aim of the present study was to clarify the endoscopic features of the extension of BCUS and verify the usefulness of the acetic acid-spraying method (AAS) for diagnosis. METHODS: A total of 25 patients with Barrett's cancer who had undergone endoscopic resection were included in this study. Histological examination of patients' resected specimens was performed to identify the presence of BCUS. Then, the endoscopic images of the BCUS cases were reviewed to summarize the findings and to evaluate the feasibility of diagnosing the extent of BCUS with each imaging technique. RESULTS: Of the 25 patients, 10 (40%) had BCUS. With white-light imaging, subtle reddish change was observed in the area of BCUS in 80% of the patients, and a flat elevated lesion was recognized in 30%. With narrow band imaging, slight brownish change was observed in the area of BCUS in 86% of the patients. Slight white changes were visualized in all cases with AAS. The extension of BCUS was correctly diagnosed by white-light imaging, narrow band imaging and AAS in 50%, 43% and 100% of the cases, respectively. Histology verified the opening of cancerous glands, which extended under the squamous epithelium, into the esophagus in the area showing slight white changes by AAS. CONCLUSION: AAS can be useful for diagnosing the extension of BCUS.

Efficacy of propofol sedation for endoscopic submucosal dissection (ESD): assessment with prospective data collection.

OBJECTIVE: The indications for endoscopic treatment in early stage cancer of the digestive tract are expanding with the emergence and technical development of endoscopic submucosal dissection (ESD). ESD requires longer term stable sedation than conventional endoscopic procedures due to the necessity of meticulous control of the devices during the procedure. Propofol has a very short half-life and can be administered continuously, which is advantageous for long-term sedation. Propofol, thus, is likely to be useful for sedation during ESD. METHODS: Fifty consecutive patients who underwent ESD for early gastric cancer with propofol sedation (Group P) and those with midazolam sedation (Group M) were included in this study. Cardiorespiratory suppression rate and the condition of arousal were compared between the groups. A questionnaire survey on the satisfaction of endoscopists, anesthesiologists, endoscopy nurses, and ward nurses with the use of propofol was also carried out. RESULTS: Respiratory suppression was observed in 50% in Group M and in 20% in Group P (p<0.05). Hypotension was seen in 14% and 36% in Groups M and P, respectively (p<0.05). No sedation-related complications were encountered in either of the groups. Arousal rates 1 hour and 3 hours after the procedure were 23% and 60% in group M and 86% and 100% in Group P (p<0.05). As for the questionnaire survey, most respondents, in particular the ward nurses, supported the use of propofol. CONCLUSION: Our data suggest that propofol is safe and useful during ESD as compared with midazolam.

Mediastinal emphysema after esophageal endoscopic submucosal dissection: its prevalence and clinical significance.

AIMS: To assess the prevalence and clinical significance of mediastinal emphysema (ME) after esophageal endoscopic submucosal dissection (ESD). METHODS: A total of 105 patients in whom assessment of ME was prospectively carried out with multi-detector row computed tomography (MDCT) after esophageal ESD were included in this study. ME was graded as follows: Grade-0, no ME; Grade-I, bubbles around the esophagus; Grade-II, ME around the thoracic aorta; Grade-III, ME extending around the heart or beyond the mediastinum into the neck; and Grade-IV, ME with pneumothorax or subcutaneous emphysema. MDCT grading was compared with the finding of conventional chest X-ray images (CXR) and clinical symptoms. RESULTS: CXR revealed the presence of ME in 6.6% of the subjects. On MDCT, ME was recognized in 62.9% (Grade-0, 37.1%; I, 46.7%; II, 10.5%; III, 5.7%; and IV, 0%), most (83.8%) being Grade-I or 0. CXR was able to visualize ME of Grade-II or greater. Exposure of the muscularis propria layer and location of the lesion were significant risk factors for development of ME of Grade-II or greater (P = 0.008 and P = 0.03, respectively). The duration of a fever of 37°C or higher was longer and the serum C-reactive protein level was higher in patients with a higher grade of ME. CONCLUSIONS: MDCT revealed the occurrence of ME in 62.9% of the patients who had undergone esophageal ESD, most of which, however, was clinically silent. Exposure of the muscular layer during ESD and location of the lesion were independent risk factors for the development of ME.

[A case of giant esophageal leiomyoma successfully resected by endoscopic submucosal dissection followed by retrieval via laparotomy].

A 30-year-old woman with chest discomfort at swallowing and occasional vomiting was referred to our department with a diagnosis of esophageal submucosal tumor. CT visualized a mass 70 mm in diameter in the middle esophagus. Esophagogastroduodenoscopy revealed a pedunculated submucosal tumor, and endoscopic resection was considered. As the size of the tumor was so large, retrieval of the resected specimen via the stomach following incision, laparotomy was planned. En bloc resection by endoscopic submucosal dissection with a Hook-knife was performed. Retrieval of the resected specimen was carried out as planned. The specimen, which was 53×48×43mm in size with a distinct margin, was diagnosed as leiomyoma derived from the muscularis mucosae histologically. Her postprocedural course was uneventful. Endoscopic resection can be chosen when an esophageal submucosal tumor is pedunculated with abundant mobility, making it possible to avoid invasive surgery.

Diagnostic efficacy of the cell block method in comparison with smear cytology of tissue samples obtained by endoscopic ultrasound-guided fine-needle aspiration.

BACKGROUND: The diagnostic efficacy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology may vary greatly depending on the treatment of the samples obtained and the level of proficiency of the cytopathologist or cytoscreener. METHODS: We prospectively evaluated the diagnostic efficacy of the cell block (CB) method and that of smear cytology using tissue samples obtained in the same needle pass at EUS-FNA in 33 patients with pancreatic tumors, abdominal tumors or swollen lymph nodes. An average of 3.1 passes were applied during the procedure without affirmation by rapid cytology. About half of the material obtained by each single pass was subjected to smear cytology, while the other half was evaluated by the CB method. Four to 12 glass slides were prepared for both Papanicolaou stain and Giemsa stain. The CB sections were prepared using the sodium alginate method and subjected to HE, PAS-AB and immunohistochemical stains. Two pathologists independently made cytological and histological diagnoses. The final diagnosis was based on integration of cytohistological findings, diagnostic imaging, and clinical course. RESULTS: The diagnostic accuracy of the CB method and that of smear cytology were 93.9 and 60.6%, respectively (p = 0.003), and their respective sensitivities were 92.0 and 60.0% (p = 0.02). It was easier to make a definite diagnosis of not only malignancies but also benign conditions by the CB method than by the smear method. CONCLUSION: The CB method with immunostaining showed a higher diagnostic yield than smear cytology in patients who had undergone EUS-FNA without rapid on-site cytology.

Long intestinal tube insertion with the ropeway method facilitated by a guidewire placed by transnasal ultrathin endoscopy for bowel obstruction.

AIM: For patients with bowel obstruction, intestinal decompression by a long tube is recommended. We assessed the usefulness of a new technique for insertion of a long tube with a guidewire placed by transnasal ultrathin endoscopy. METHODS: Nineteen patients who had been diagnosed as suffering from bowel obstruction underwent long-tube insertion with the ropeway technique using a guidewire placed by transnasal endoscopy. Thirty-three patients who had undergone conventional insertion of a long tube were included as controls. The success rate of intubation of the small bowel and the time required for the procedure were compared between the subjects and controls. RESULTS: The success rate of intubation was 94.7% (18/19) in subjects and 84.8% (28/33) in controls (P = 0.53). The time required for insertion in the subjects and controls was 24.1 +/- 8.1 min and 48.7 +/- 25.3 min, respectively, with a statistically significant difference (P < 0.001). No complications relevant to the procedure were encountered in either of the groups. CONCLUSION: Long-tube insertion facilitated by transnasal endoscopy reduces the time required for insertion in comparison with the conventional technique without endoscopy. Endoscopy-assisted long-tube insertion with the ropeway method is a safe and useful procedure for decompression in patients with bowel obstruction.

Snare-over-the-wire technique for safe exchange of a stent following endosonography-guided biliary drainage.

Endosonography-guided biliary drainage (ESBD) is a new option that allows establishment of biliary drainage. Due to the diameter of the working channel of an echoendoscope, it is necessary to replace a small caliber stent with a larger one to lessen the risk of stent occlusion. However, insertion of a guidewire into the bile duct via the hole of the sinus tract following direct removal of a previously placed stent is not always possible, resulting in guidewire passage outside the fistula and bile leakage. Cannulation of the previously deployed stent, guidewire insertion into the bile duct via the cannula and the stent, and removal of the stent with the snare over the guidewire leaving the guidewire in place (the snare-over-the-wire technique [SOW]) for stent exchange following ESBD was attempted. Four patients who required stent exchange following ESBD were included in the present study to evaluate the feasibility and usefulness of SOW. SOW was successful in all the cases. A new stent was also successfully deployed over the guidewire in all the cases. No complications were encountered. The snare-over-the-wire technique is feasible and useful in stent exchange following ESBD for the reduction of the risk of guidewire migration.

Long-tube insertion with the ropeway method facilitated by a guidewire placed by transnasal ultrathin endoscopy for bowel obstruction: a prospective, randomized, controlled trial.

BACKGROUND: It is often difficult to insert a long intestinal tube in the small bowel of patients with bowel obstruction, and it often results in long procedure time and severe patient distress. OBJECTIVE: To assess the usefulness of the ropeway method by using a guidewire placed with the assistance of transnasal ultrathin endoscopy in long-tube insertion for patients with bowel obstruction. DESIGN: Prospective, randomized, controlled, single-center study. PATIENTS AND INTERVENTIONS: Thirty-four consecutive patients with bowel obstruction requiring decompression participated in the study and were randomized to the insertion of a long tube with the ropeway method (ILTR) group (ie, insertion along an endoscopically placed guidewire that was passed through only the distal 4 cm of the tube) or insertion by a conventional method group (C group). MAIN OUTCOME MEASUREMENTS: The time required for the procedure (main), success rate, x-ray exposure time, and intensity of patient distress measured with a visual analog scale of 1 to 5 (better to worse). RESULTS: The mean (+/- standard deviation) duration of the procedure in the successful cases in the ILTR group and the C group was 16.1 +/- 5.6 minutes and 26.4 +/- 13.8 minutes, respectively (P = .010). The success rate was 100% in the ILTR group and 88% in the C group (P = .48). The mean (+/- standard deviation) x-ray exposure time and intensity of patient distress were, respectively, 16.4 +/- 8.7 minutes and 33.2 +/- 12.3 minutes (P < .001) and 2.6 +/- 0.7 and 3.7 +/- 1.2 (P = .016). LIMITATIONS: Single-center study and small sample size to evaluate overall safety. CONCLUSIONS: Long-tube insertion for bowel obstruction with the ropeway method facilitated by transnasal ultrathin endoscopy was superior to conventional fluoroscopic placement with regard to overall procedure success, time required, and patient comfort.

Impact of a transparent hood on the performance of total colonoscopy: a randomized controlled trial.

BACKGROUND: Clinical demand for total colonoscopy (TCS) is increasing. Improvement of the cecal intubation rate and shortening of the examination time would expand the capacity for TCS. OBJECTIVE: To assess the efficacy of a transparent hood attached to the tip of a colonoscope for cecal intubation in TCS. DESIGN: Prospective, randomized, controlled study. SETTING: Single tertiary-referral center. INTERVENTIONS: TCS. MAIN OUTCOME MEASUREMENTS: Cecal intubation time and rate, complications, patient discomfort, and detection rate of colonic polyps. METHODS: Patients who were to undergo screening and/or surveillance TCS for colorectal cancer were invited to participate in the study. Cecal intubation time and rate, complications, patient discomfort, and detection rate of colonic polyps were evaluated. RESULTS: A total of 592 patients enrolled in this study were randomly allocated to the hood group and no-hood group. The mean (SD) cecal intubation time in the hood group and the no-hood group was 10.2 +/- 12.5 minutes and 13.4 +/- 15.8 minutes, respectively (P = .0241). The effect of its use was more prominent in the expert endoscopists group compared with those with moderate experience. The cecal intubation rate and the detection rate of small polyps in the 2 groups were similar. The grade of patient discomfort was significantly lower in the hood group. No complications were encountered with the use of the hood. CONCLUSIONS: Use of a transparent hood on the tip of a colonoscope shortened the time required for cecal intubation and decreased patient discomfort; such use was more effective among experts in shortening the examination time.

Temporary endosonography-guided biliary drainage for transgastrointestinal deployment of a self-expandable metallic stent.

Endosonography-guided biliary drainage (ESBD) is now gaining acceptance as a useful alternative for the management of obstructive jaundice.(1) At present, ESBD is used mainly to establish an anastomosis between the biliary tree and the duodenum, stomach, jejunum, or esophagus by placing a stent so as to bridge the bile duct and alimentary tract. We herein report a new application of ESBD, that is, its temporary use for gaining access to the bile duct in order to deploy a self-expandable metallic stent (SEMS) via the transhepatic route. In a patient with pylorus stenosis due to advanced gastric cancer with extrahepatic bile duct obstruction caused by nodal metastasis, a plastic stent was placed temporarily by ESBD to bridge the esophagus and the left hepatic duct. Ten days later, the stent was retrieved, leaving a guidewire in the bile duct, and a delivery unit of a SEMS was introduced into the bile duct over the guidewire via the sinus tract. The SEMS was then successfully deployed through the stenosis. No stent was left in the sinus tract. This procedure yields a mature fistula through which a delivery unit can be safely introduced into the bile duct followed by uneventful deployment of a SEMS.

Amylase levels in bile in patients with a morphologically normal pancreaticobiliary ductal arrangement.

BACKGROUND: We investigated the presence of occult pancreaticobiliary reflux in patients with a morphologically normal pancreaticobiliary ductal arrangement by measuring biliary amylase levels and compared histopathological findings of the gallbladder between groups with high and low biliary amylase levels. METHODS: In 178 patients with a normal pancreaticobiliary ductal arrangement who had undergone endoscopic retrograde cholangiopancreatography (ERCP), we sampled bile from the bile duct and measured amylase levels. Then we compared clinical features and histological findings of the gallbladder between high (HALG) and low amylase level groups (LALG). RESULTS: A high biliary amylase level was observed in 25.8% (46/178) of the patients. The prevalence of a high biliary amylase level was high in patients with gallbladder carcinoma (40%) and in those with choledocholithiasis (28.4%). The level of amylase in bile was high in patients with gallbladder carcinoma, adenomyomatosis of the gallbladder, and chronic cholecystitis. A strong correlation between the levels of amylase and lipase in bile and the dominance of amylase of pancreatic origin in bile were confirmed by isozyme analysis. Thickening of the gallbladder mucosa was a significant manifestation in HALG. Histological examination of the gallbladder mucosa showed that incidences of metaplastic change and atypical epithelium and Ki67-LI in were higher in HALG than in LALG. CONCLUSIONS: Occult pancreaticobiliary reflux is observed in a considerable number of ERCP candidates. Those who show an extremely high biliary amylase level, at least, may be at high risk for biliary malignancies.

Endoscopic biliary imaging and clinicopathological features of cystic duct cancer.

BACKGROUND: Cystic duct cancer fulfilling Farrar's criteria is relatively rare, but tumors whose origin is estimated to be in the cystic duct exist. The clinical features of such "broadly defined" cystic duct cancer have not been clarified. METHODS: The endoscopic retrograde cholangiography (ERC) findings, intraductal ultrasonography (IDUS) findings, histological findings, and prognoses of 11 cases of cystic duct cancers resected at our institution (group C) were retrospectively analyzed. As a control group, 55 cases of middle or lower bile duct cancer (group B) were used (in 20 of the 55 cases of group B, tumors extended to the cystic duct intraluminally (group B-C (+)). RESULTS: (1) ERC findings of group C as compared with those of group B-C (+) were as follows: (a) unilateral bile duct narrowing (spoon-like appearance): 55% versus 5% (P<0.01); (b) bilateral bile duct narrowing (apple-core-like appearance): 27% versus 95% (P<0.001). (2) IDUS was unable to visualize the cysticocholedochal junction (negative "confluence sign") more often in group C (67%) than in group B-C (+) (13%) (P<0.01). (3) Histologically, tumors extended to the gallbladder and the bile duct in 36% and 91% of the cases in group C, respectively. (4) The median survival time of the two groups was 21 and 28 months, respectively. CONCLUSIONS: Cystic duct cancers frequently extended to the bile duct. The spoon-like appearance by ERC and the negative confluence sign by IDUS were characteristic findings.

Clinicopathological study on the intraductal spread of small pancreatic cancer.

BACKGROUND: The aim of this study was to evaluate histopathologically the frequency, direction, and length of intraductal spread (IS) along the main pancreatic duct from the main tumor of small pancreatic cancer. METHODS: Resected specimens from 20 cases of pTS1 (histologically 2 cm or less in diameter) pancreatic cancer (September 1983 to December 2005) were examined histopathologically. As controls, 40 resected specimens from cases of pTS2 (more than 2 cm and less than 4 cm in diameter) or larger sized pancreatic cancer (pTS2

Histological study of gallbladder and bile duct epithelia in patients with anomalous arrangement of the pancreaticobiliary ductal system: comparison between those with and without a dilated common bile duct.

BACKGROUND: We histologically evaluated the epithelia of the gallbladder (GB) and bile duct (BD) in patients with anomalous arrangement of the pancreaticobiliary ductal system (AAPB), with regard to the shape of the common BD (CBD). METHODS: The GB and BD were studied histologically using surgical materials from 44 patients with AAPB: 27 with a dilated CBD (D-type) and 17 with a nondilated CBD (N-type). RESULTS: GB cancer and BD cancer were found in 11.1% and 3.7% of D-type and 17.6% and 0% of N-type respectively. Hyperplastic epithelium and atypical epithelium of the GB were frequently seen in both D-type (46%, 46%) and N-type (82%, 70%), while such epithelia of the BD were only seen in D-type (10%, 35%). The Ki67 labeling index of the nonneoplastic epithelium of the GB was high in both D-type (13.0%) and N-type (9.7%), though that of the BD was high in D-type (12.5%) but low in N-type (1.8%). The prevalences of pyloric gland metaplasia, intestinal metaplasia, and p53 protein overexpression of the nonneoplastic epithelium did not show any significant differences between D-type and N-type. CONCLUSIONS: It is suggested that the BD epithelium of N-type probably has a lower potential for developing malignancy than that of D-type, while the GB epithelia of both D-type and N-type have a high potential for developing malignancy. This might support the selection of simple cholecystectomy as the treatment of choice in AAPB patients of N-type, although further investigation of the BD epithelium is required in a larger number of such patients.