Template Synthesis of Disilacycloalkanes Utilizing the Reactivity of a Siloxane Bond.

The investigation of large and flexible macrocyclic compounds has garnered significant attention due to their functions as host molecules and linkers. Although the synthetic yields of such compounds, achieved by linking two molecular fragments, are often hindered by the flexibility of the molecular skeleton, one of the effective solutions is template synthesis for the macrocycles. In this study, a novel template synthesis for disilacycloalkanes by leveraging the reactivity of a siloxane bond was investigated. The yields obtained through the template methods surpassed those of the nontemplate approach, and the introduction of substituents to the silicon atoms was also accomplished with success. All of the resulting disilacycloalkanes crystallized exceptionally well, enabling their structural determination through X-ray crystallography. Notably, the stability of these structures was elucidated by analyzing dispersion forces between alkyl chains, using density functional theory (DFT) calculations. This template synthesis method demonstrates its efficacy in synthesizing molecular systems that encompass two functional moieties linked with macroalkanes.

Study of myopia progression and risk factors in Hubei children aged 7-10 years using machine learning: a longitudinal cohort.

BACKGROUND: To investigate the trend of refractive error among elementary school students in grades 1 to 3 in Hubei Province, analyze the relevant factors affecting myopia progression, and develop a model to predict myopia progression and the risk of developing high myopia in children. METHODS: Longitudinal study. Using a cluster-stratified sampling method, elementary school students in grades 1 to 3 (15,512 in total) from 17 cities in Hubei Province were included as study subjects. Visual acuity, cycloplegic autorefraction, and height and weight measurements were performed for three consecutive years from 2019 to 2021. Basic information about the students, parental myopia and education level, and the students' behavioral habits of using the eyes were collected through questionnaires. RESULTS: The baseline refractive errors of children in grades 1 ~ 3 in Hubei Province in 2019 were 0.20 (0.11, 0.27)D, -0.14 (-0.21, 0.06)D, and - 0.29 (-0.37, -0.22)D, respectively, and the annual myopia progression was - 0.65 (-0.74, -0.63)D, -0.61 (-0.73, -0.59)D and - 0.59 (-0.64, -0.51)D, with the prevalence of myopia increasing from 17.56%, 20.9%, and 34.08% in 2019 to 24.16%, 32.24%, and 40.37% in 2021 (Χ2 = 63.29, P < 0.001). With growth, children's refractive error moved toward myopia, and the quantity of myopic progression gradually diminished. (F = 291.04, P = 0.027). The myopia progression in boys was less than that in girls in the same grade (P < 0.001). The change in spherical equivalent refraction in myopic children was smaller than that in hyperopic and emmetropic children (F = 59.28, P < 0.001), in which the refractive change in mild myopia, moderate myopia, and high myopia children gradually increased (F = 73.12, P < 0.001). Large baseline refractive error, large body mass index, and high frequency of eating sweets were risk factors for myopia progression, while parental intervention and strong eye-care awareness were protective factors for delaying myopia progression. The nomogram graph predicted the probability of developing high myopia in children and found that baseline refraction had the greatest predictive value. CONCLUSION: Myopia progression varies by age, sex, and myopia severity. Baseline refraction is the most important factor in predicting high myopia in childhood. we should focus on children with large baseline refraction or young age of onset of myopia in clinical myopia prevention and control.

A machine-learning approach to discerning prevalence and causes of myopia among elementary students in Hubei.

OBJECTIVE: Our aim is to establish a machine-learning model that will enable us to investigate the key factors influencing the prevalence of myopia in students. METHODS: We performed a cross-sectional study that included 16,653 students from grades 1-3 across 17 cities in Hubei Province. We used questionnaires to discern levels of participation in potential factors contributing to the development of myopia. The relative importance of potential contributors was ranked using machine-learning methods. The students' visual acuity (VA) was measured and those with logMAR VA of > 0.0 underwent a autorefraction test to determine students' refraction status. RESULTS: The prevalence of myopia in grades 1, 2, and 3 was 14.70%, 20.54% and 28.93%, respectively. Myopia rates among primary school students in provincial capital city (32.35%) were higher than those in other urban (23.03%) and rural (14.82%) areas. Children with non-myopic parents, only one myopic parent, or both parents having myopia exhibited myopic rates of 16.36%, 25.18%, and 41.37%, respectively. Myopia prevalence was higher in the students who continued to use their eyes at close range for a long time and lower in those engaged longer in outdoor activities. The machine-learning model determined that the top three contributing factors were the students' age (0.36), followed by place of residence (0.34), starting age of education (0.21). CONCLUSION: The overall prevalence of myopia was 21.52%. Children's age and place of residence were the important influencing factors, but genetics and environmental were also played key roles in myopia development.

Endocrine cells in ampullary carcinoma.

BACKGROUND/PURPOSE: As ampullary carcinoma originates from four anatomical regions, it may have different behaviors depending on its origin. We documented the presence of endocrine cells found in ampullary carcinoma, and we studied the clinicopathological implications of their presence. METHODS: We immunohistochemically examined the presence of an endocrine component in 62 surgically resected specimens of ampullary carcinoma, and we studied the clinicopathological differences between endocrine component-positive cases and endocrine component-negative cases. RESULTS: Endocrine cells were detected in 16 cases (26%); 11 cases had many endocrine cells, and five cases had scattered endocrine cells. Serotonin-positive cells were detected in all 16 cases, in which six cases had many positive cells. Several somatostatin-positive cells were detected in three cases. Endocrine cells were detected in ampulloduodenal polypoid lesions (two cases) and ampullopancreaticobiliary ducts (14 cases). The histology of 15 of the 16 endocrine component-positive ampullary carcinomas was the intestinal type. Pancreatic invasion and lymph node involvement were observed less frequently in endocrine component-positive cases (P < 0.01). There were no significant differences with respect to immunoreactivity for carbohydrate antigen (CA) 19.9, carcinembryonic antigen (CEA), and p53 overexpression, and K-ras mutations. CONCLUSIONS: Endocrine component-positive ampullary carcinoma seemed to be derived from the ampullopancreaticobiliary common duct or the ampulloduodenum, and to behave less aggressively than endocrine component-negative carcinoma.

A new diagnostic endoscopic tool for autoimmune pancreatitis.

BACKGROUND: Autoimmune pancreatitis (AIP) is a type of pancreatitis that is presumed to have an autoimmune etiology, and is currently diagnosed based on a combination of clinical, laboratory, and imaging studies. Although it is of utmost importance that AIP be differentiated from pancreatic cancer, AIP is sometimes difficult to differentiate from locally advanced pancreatic cancer. OBJECTIVE: To find a useful new method to diagnose AIP. DESIGN: Prospective study from June 2004 to September 2007. SETTING: Single public hospital. PATIENTS: Ten AIP patients, 10 patients with pancreatic cancer, and 10 patients with papillitis. INTERVENTIONS: Immunoglobulin (Ig)G4-immunostaining of biopsy specimens obtained from the major duodenal papilla. MAIN OUTCOME MEASUREMENTS: Number of immunohistochemically identified cells per high-power field (HPF) in each specimen were counted. RESULTS: Significant infiltration of IgG4-positive plasma cells (> or = 10/HPF) was observed in the major duodenal papilla of all 8 AIP patients with pancreatic head involvement. Moderate infiltration of IgG4-positive plasma cells (4-9/HPF) was detected in 1 patient with pancreatic head cancer, but there were rare (< or = 3/HPF) IgG4-positive plasma cells infiltrating the major duodenal papilla in 2 AIP patients who only had pancreatic body and/or tail involvement, 9 patients with pancreatic cancer, and 10 patients with papillitis. In the 3 AIP patients in whom biopsy specimens were retaken after steroid therapy, the number of IgG4-positive plasma cells decreased from significant to moderate in 2 patients and to < or = 3/HPF in 1 patient. LIMITATIONS: Small sample size. Endoscopists were not blinded to clinical information. CONCLUSIONS: IgG4 immunostaining of biopsy specimens obtained from the major duodenal papilla may be useful for supporting a diagnosis of AIP with pancreatic head involvement.

Sex-based differences in gallbladder cancer associated with pancreaticobiliary maljunction.

BACKGROUND/AIMS: Gallbladder cancer predominantly affects women; this sex-based difference is influenced by factors such as gallstones, sex hormone and genetic susceptibility. Gallbladder cancer is also frequently associated with pancreaticobiliary maljunction (PBM) without biliary dilatation. We examined sex-based differences in gallbladder cancer associated with PBM. METHODOLOGY: With a particular focus on gender differences, we retrospectively compared clinicopathological findings between 44 patients (9 men, 35 women) with PBM without biliary dilatation and 232 patients (60 men, 172 women) with gallbladder cancer that was not associated with PBM. RESULTS: Gallbladder cancer was detected in 75% of patients with PBM without biliary dilatation. Among PBM patients, gallbladder cancer was significantly more common in women than in men [29/35 (83%) us. 4/9 (44%), p<0.05]. Both men and women with gallbladder cancer associated with PBM were significantly younger at the time of diagnosis than patients with gallbladder cancer without PBM (p<0.01). Gallstones were detected in only 10% of women with gallbladder cancer with PBM, while gallstones were detected in 63% of women with gallbladder cancer without PBM (p<0.01). CONCLUSIONS: Gallbladder cancer occurs very frequently in patients with PBM without biliary dilatation, and women appear to be at a significantly higher risk than men.

Pancreas divisum in pancreaticobiliary maljunction.

BACKGROUND/AIMS: Pancreaticobiliary maljunction (PBM) and pancreas divisum (PD) are congenital anomalies that develop in the embryo at an early stage. They are possibly the result of bile and pancreatic duct misarrangement. We investigated the configuration of the pancreatic duct in patients with PBM and its clinical implications. METHODOLOGY: In 84 PBM patients, the configuration of the pancreatic duct and the presence of biliary cancer were documented. Patency of Santorini's duct was determined fluoroscopically or by dye-injection endoscopic retrograde pancreatography. Bile amylase levels were measured in 10 patients. RESULTS: Incomplete PD was detected in 8 (9.5%) of the 84 PBM patients. All of the 8 patients had a patent Santorini's duct, and only 1 patient had gallbladder cancer. The frequency of associated gallbladder cancer and the bile amylase level were significantly lower in PBM patients with a patent Santorini's duct than in PBM patients with a nonpatent Santorini's duct. CONCLUSIONS: PBM is sometimes associated with incomplete PD. In PBM patients with an incomplete PD, the incidence of cancer of the biliary tract may be lower, since pancreatic juice reflux into the bile duct might be reduced by the flow of pancreatic juice into the duodenum through Santorini's duct.

Carcinoma arising in congenital choledochal cysts.

BACKGROUND/AIMS: Congenital choledochal cyst is almost always associated with pancreaticobiliary maljunction and is sometimes associated with biliary carcinoma. This study aimed to investigate the clinicopathological features and surgical treatment of choledochal cyst associated with carcinoma arising in the cyst wall. METHODOLOGY: Relationship of the clinicopathological findings and surgical treatment of 8 patients with histologically proven carcinoma that had developed in the choledochal cyst wall were examined to determine mode of tumor spread, multicentric tumor origins, and coincidence with other neoplastic lesions. RESULTS: Papillary adenocarcinoma (n = 5) had different clinicopathological features than tubular adenocarcinoma (n = 3). Radiologically, papillary adenocarcinoma presented as an eccentrically located polypoid mass in the cyst, while with tubular adenocarcinoma, there was evidence of bile duct stenosis with irregular thickening of the bile duct wall. Papillary adenocarcinoma was associated with extensive superficial spread (n = 1), synchronous (n = 2), or metachronous (n = 2) multicentric tumors. Pancreatoduodenectomy with (n = 1) or without (n = 1) hepatic lobectomy, and repeated resection by hepatic lobectomy (n = 2) were performed for these circumstances of tumors. Extensive or repeated resections allowed 3 patients to live longer than 2 years. Tubular adenocarcinoma was associated with scirrhously infiltrative spread and a poor prognosis. CONCLUSIONS: Papillary adenocarcinoma frequently occurs in the choledochal cyst wall. Since aggressive resection offers survival benefits in papillary adenocarcinoma arising in the choledochal cyst wall, the presence of superficial spread and multicentric tumors should be identified and taken into account when planning surgery. Patients require close monitoring so that recurrent carcinoma of the remnant bile duct can be identified early.

The incidence of pancreatic and extrapancreatic cancers in Japanese patients with chronic pancreatitis.

BACKGROUND/AIMS: Although an association between chronic pancreatitis and malignancies has been reported in the Western literature, in Japan there have been few reports that have dealt with this issue. We investigated the incidence of pancreatic and extrapancreatic cancers in Japanese patients with chronic pancreatitis. METHODOLOGY: We studied 170 Japanese patients with definite chronic pancreatitis with respect to the occurrence of pancreatic and extrapancreatic cancers during follow-up and compared the incidence with that reported in the Western literature. RESULTS: The patients developed 29 cancers including 5 pancreatic cancers. Four patients had two different types of cancer. The extrapancreatic cancer incidence (24/170: 14.1%) was significantly higher than in the West (8.3%, p < 0.01). The major organs in which cancer developed were stomach (n=9), pancreas (n=5), esophagus (n=4), colon (n=3), lung (n=2) and hemopoietic tissue (n=2). The overall incidence (8.2%) of associated cancers of the digestive system including, stomach, intestine, liver, biliary duct, and gallbladder, was significantly higher than in the West (1.3%, p < 0.01). CONCLUSIONS: The risk of extrapancreatic cancers during the course of chronic pancreatitis is significantly increased in Japan than in Western countries. In particular, cancers of the digestive system are frequently associated with chronic pancreatitis in Japan.

Autoimmune pancreatitis metachronously associated with retroperitoneal fibrosis with IgG4-positive plasma cell infiltration.

Retroperitoneal fibrosis is an uncommon disorder characterized by the formation of a dense plaque of fibrous tissue in the retroperitoneum, and its etiology remains unknown. Autoimmune pancreatitis is a rare type of chronic pancreatitis characterized by fibrosis with abundant infiltration of IgG4-positive plasma cells and lymphocytes and obliterative phlebitis in the pancreas. We present a case of autoimmune pancreatitis that developed 10 mo after the occurrence of retroperitoneal fibrosis. Histological findings of the resected retroperitoneal mass were marked periureteral fibrosis with abundant infiltration of IgG4-positive plasma cells and lymphocytes and obliterative phlebitis. These findings suggest a common pathophysiological mechanism for retroperitoneal fibrosis and autoimmune pancreatitis in this case. Some cases of retroperitoneal fibrosis might be a retroperitoneal lesion of IgG4-related sclerosing disease.

Involvement of pancreatic and bile ducts in autoimmune pancreatitis.

AIM: To examine the involvement of the pancreatic and bile ducts in patients with autoimmune pancreatitis. METHODS: Clinical and cholangiopancreatographic findings of 28 patients with autoimmune pancreatitis were evaluated. For the purposes of this study, the pancreatic duct system was divided into three portions: the ventral pancreatic duct; the head portion of the dorsal pancreatic duct; and the body and tail of the dorsal pancreatic duct. RESULTS: Both the ventral and dorsal pancreatic ducts were involved in 24 patients, while in 4 patients only the dorsal pancreatic duct was involved. Marked stricture of the bile duct was detected in 20 patients and their initial symptom was obstructive jaundice. Six patients showed moderate stenosis to 30%-40% of the normal diameter, and the other two patients showed no stenosis of the bile duct. Although marked stricture of the bile duct was detected in 83% (20/24) of patients who showed narrowing of both the ventral and dorsal pancreatic ducts, it was not observed in the 4 patients who showed involvement of the dorsal pancreatic duct alone (P=0.0034). CONCLUSION: Both the ventral and dorsal pancreatic and bile ducts are involved in patients with autoimmune pancreatitis.

Usefulness of biopsying the major duodenal papilla to diagnose autoimmune pancreatitis: a prospective study using IgG4-immunostaining.

AIM: To examine the histological and immunohistochemical findings of biopsy specimens taken from the major duodenal papilla of autoimmune pancreatitis (AIP) patients. METHODS: The major duodenal papilla in the resected pancreas of 3 patients with AIP and of 5 control patients [pancreatic carcinoma (n = 3) and chronic alcoholic pancreatitis (n = 2)] was immunostained using anti-CD4-T cell, CD8-T cell and IgG4 antibodies. Forceps biopsy specimens taken from the major duodenal papilla of 2 patients with AIP and 5 control patients with suspected papillitis were prospectively taken during duodenoscopy and immunohistochemically examined. RESULTS: Moderate or severe lymphoplasmacytic infiltration including many CD4-positive or CD8-positive T lymphocytes and IgG4-positive plasma cells (>or=10/HPF), was observed in the major duodenal papilla of all 3 patients with AIP. The same findings were also detected in the biopsy specimens taken from the major duodenal papilla of 2 patients with AIP, but in controls, there were only a few (

Sclerosing cholecystitis associated with autoimmune pancreatitis.

AIM: To evaluate the histopathological and radiological findings of the gallbladder in patients with autoimmune pancreatitis (AIP). METHODS: The radiological findings of the gallbladder of 19 AIP patients were retrospectively reviewed. Resected gallbladders of 8 AIP patients were examined histologically and were immunostained with anti-IgG4 antibody. Controls consisted of gallbladders resected for symptomatic gallstones (n = 10) and those removed during pancreatoduodenectomy for pancreatic carcinoma (n = 10), as well as extrahepatic bile ducts and pancreases removed by pancreatoduodenectomy for pancreatic carcinoma (n = 10). RESULTS: Thickening of the gallbladder wall was detected by ultrasound and/or computed tomography in 10 patients with AIP (3 severe and 7 moderate); in these patients severe stenosis of the extrahepatic bile duct was also noted. Histologically, thickening of the gallbladder was detected in 6 of 8 (75%) patients with AIP; 4 cases had transmural lymphoplasmacytic infiltration with fibrosis, and 2 cases had mucosal-based lymphoplasmacytic infiltration. Considerable transmural thickening of the extrahepatic bile duct wall with dense fibrosis and diffuse lymphoplasmacytic infiltration was detected in 7 patients. Immunohistochemically, severe or moderate infiltration of IgG4-positive plasma cells was detected in the gallbladder, bile duct, and pancreas of all 8 patients, but was not detected in controls. CONCLUSION: Gallbladder wall thickening with fibrosis and abundant infiltration of IgG4-positive plasma cells is frequently detected in patients with AIP. We propose the use of a new term, sclerosing cholecystitis, for these cases that are induced by the same mechanism as sclerosing pancreatitis or sclerosing cholangitis in AIP.

Pancreatic cancer with a high serum IgG4 concentration.

Differentiation between autoimmune pancreatitis and pancreatic cancer is sometimes difficult. It has been reported that serum IgG4 concentrations are significantly elevated and particularly high (>135 mg/dL) in autoimmune pancreatitis. Measurement of serum IgG4 has become a useful tool for differentiating between autoimmune pancreatitis and pancreatic cancer. However, we present a 74-year-old female with a markedly elevated serum IgG4 (433 mg/dL) who underwent pancreaticoduodenectomy for pancreatic cancer. Elevated serum IgG4 levels continued after the resection. On histology, adenocarcinoma of the pancreas accompanied with moderate lymphoplasmacytic infiltration infiltrated the lower bile duct and duodenum, but there were no findings of autoimmune pancreatitis. Although a small metastasis was detected in one parapancreatic lymph node, regional lymph nodes were swollen. Abundant IgG4-positive plasma cells infiltrated the cancerous areas of the pancreas, but only a few IgG4-positive plasma cells were detected in the noncancerous areas. Pancreatic cancer cells were not immunoreactive for IgG4. An abundant infiltration of IgG4-positive plasma cells was detected in the swollen regional lymph nodes and in the duodenal mucosa. We believe that the serum IgG4 level was elevated in this patient with pancreatic cancer as the result of an IgG4-related systemic disease that had no clinical manifestations other than lymphadenopathy.

MRCP and MRI findings in 9 patients with autoimmune pancreatitis.

AIM: To evaluate magnetic resonance cholangiopancreatography (MRCP) findings in conjunction with magnetic resonance (MR) images in autoimmune pancreatitis (AIP) patients. METHODS: Nine patients with AIP underwent MRI, MRCP, endoscopic retrograde cholangiopancreatography (ERCP), computed tomography, and ultrasonography. The MRCP and MR images taken before and after steroid therapy were reviewed and compared with other imaging modalities. The MRCP findings of the AIP cases were compared to those of 10 cases with carcinoma of the head of the pancreas. RESULTS: On MRCP, the narrowed portion of the main pancreatic duct noted on ERCP was not visualized, while the non-involved segments of the main pancreatic duct were visualized. The degree of upstream dilatation of the proximal main pancreatic duct was milder than that seen in cases of pancreatic carcinoma. Stenosis or obstruction of the lower bile duct was detected in 8 patients. MR images showed enlargement of the pancreas with decreased signal intensity on T1-weighted MR images, increased signal intensity on T2-weighted MR images, and, in 3 patients, a hypointense capsule-like rim. After steroid therapy, the previously not visualized portion of the main pancreatic duct was seen, along with improvement of the bile duct stenosis. Pancreatic enlargement decreased, and the abnormal signal intensity on both T1- and T2-weighted MR images became isointense. CONCLUSION: MRCP cannot differentiate irregular narrowing of the main pancreatic duct seen with AIP from stenosis of the main pancreatic duct seen with pancreatic carcinoma. However, MRCP findings in conjunction with MR imaging of pancreatic enlargement that shows abnormal signal intensity on T1- and T2-weighted MR images are useful in supporting a diagnosis of AIP.

Clinical implications of incomplete pancreas divisum.

CONTEXT: Incomplete pancreas divisum is a pancreatic anomaly that results in an inadequate communication between the ventral and dorsal pancreatic ducts. Although the relationship between complete pancreas divisum and pancreatitis has been contentious, clinical implications of incomplete pancreas divisum have not been noted. OBJECTIVE: This study was done to investigate the clinical significance of incomplete pancreas divisum. PATIENTS AND METHODS: We studied the anatomy of the pancreatic duct system in 3,220 cases using endoscopic retrograde pancreatography; 44 cases had complete pancreas divisum, and 41 had incomplete pancreas divisum. MAIN OUTCOME MEASURE: The prevalence of chronic and acute pancreatitis associated with complete or incomplete pancreas divisum was compared with that of cases with neither complete nor incomplete pancreas divisum (controls). RESULTS: All of the patients with complete or incomplete pancreas divisum who abused alcohol had chronic or acute pancreatitis. The prevalence of chronic pancreatitis in patients with complete or incomplete pancreas divisum was significantly higher than in controls (P<0.001 and P=0.001, respectively), but acute pancreatitis occurred more frequently only in patients with complete pancreas divisum (P=0.010). When we considered pancreatic-type pain as a pancreatitis-like disease, complete and incomplete pancreas divisum were suspected as the cause of pancreatitis-like disease in 39% (15/38: chronic dorsal pancreatitis, n=5; acute pancreatitis, n=7; pancreatic-type pain, n=3) and 30% (10/33: chronic dorsal pancreatitis, n=2; acute relapsing pancreatitis, n=1; pancreatic-type pain, n=7) of patients who did not abuse alcohol, respectively. CONCLUSIONS: Although the precise pathophysiology may differ, patients with complete pancreas divisum and patients with incomplete pancreas divisum may have similar presentations and a similar prevalence. The clinical implications of incomplete pancreas divisum may be similar to those of complete pancreas divisum.

Pancreaticopleural fistula visualized by computed tomography scan combined with pancreatography.

CONTEXT: We report a case of a pancreaticopleural fistula which was clearly demonstrated by computed tomography (CT) scan following pancreatography and which was successfully treated with endoscopic nasopancreatic drainage combined with octreotide. CASE REPORT: A 52-year-old male was admitted to our hospital for additionally evaluation of bilateral pleural effusion. The pleural fluid amylase level was markedly elevated. Endoscopic retrograde pancreatography showed a cyst in the body of the pancreas and extravasation of contrast medium extending cranially from the cyst. The disease was treated successfully with endoscopic nasopancreatic drainage combined with the administration of octreotide. A pancreaticopleural fistulous route was clearly demonstrated by CT scan following pancreatography through the nasopancreatic drainage tube. CONCLUSIONS: A CT scan following pancreatography was useful in demonstrating a pancreaticopleural fistulous route.

Biliary carcinoma risk in patients with pancreaticobiliary maljunction and the degree of extrahepatic bile duct dilatation.

BACKGROUND/AIMS: Pancreaticobiliary maljunction (PBM) carries a high risk of biliary carcinoma. This study aimed to examine the biliary complications of patients with PBM in relation to the degree of extra-hepatic bile duct dilatation. METHODOLOGY: Ninety-eight cases of PBM could be divided into 5 groups according to the maximum diameter of the extrahepatic bile duct: < or = 10mm, 11-15mm, 16-20mm, 21-30mm, > or = 31mm. The clinicopathological findings of biliary carcinomas associated with PBM were compared with 232 cases of gallbladder carcinoma and 159 cases of bile duct carcinoma that were not associated with PBM. RESULTS: Gallbladder carcinoma occurred in 36 of 65 patients (55%) with PBM whose maximum diameter of the extrahepatic bile duct was < or = 30mm, but no gallbladder carcinoma occurred in patients with PBM whose diameter was > or = 31mm. Bile duct carcinoma occurred in 6 of 52 patients (12%) with PBM whose diameter was > or = 21mm, but no bile duct carcinoma occurred in patients with PBM whose diameter was < or = 20mm. The age at diagnosis of the patients with gallbladder or bile duct carcinoma associated with PBM was significantly younger than those without PBM (p<0.01). CONCLUSIONS: PBM with an extrahepatic bile duct diameter < or = 30mm is associated with a high risk of gallbladder carcinoma. PBM with an extrahepatic bile duct diameter > or = 21mm is associated with a high risk of bile duct carcinoma. Prophylactic cholecystectomy is recommended for patients with PBM without biliary dilatation.

Malignancies associated with intraductal papillary mucinous neoplasm of the pancreas.

AIM: As intraductal papillary mucinous neoplasm (IPMN) has a favorable prognosis, associated malignancies have potential significance in these patients. We examined the incidence and characteristics of pre-existing, coexisting and subsequent malignancies in patients with IPMN. METHODS: Seventy-nine cases of IPMN were diagnosed by detection of mucous in the pancreatic duct during endoscopic retrograde pancreatography. Histological diagnosis was confirmed in 30 cases (adenoma (n = 19) and adenocarcinoma (n = 11). Other primary malignancies associated with IPMN, occurring in the prediagnostic or postdiagnostic period, were investigated. Postdiagnostic follow-up period was 3.3+/-0.5 years (range, 0.2-20 years). RESULTS: Other 40 malignancies occurred in 28 patients (35%). They were found before (n = 15), at (n = 19) and after (n = 6) the diagnosis of IPMT. Major associated malignancies were gastric cancer (n = 12), colonic cancer (n = 7), esophageal cancer (n = 4), pulmonary cancer (n = 4), and independent pancreatic cancer (n = 3). Pancreatic cancer was synchronous with IPMN in two patients and metachronous in one (3 years after diagnosis of IPMN). Thirty-one lesions were treated surgically or endoscopically. Fourteen patients died of associated cancers. Development of other malignancies was related to age (71.9+/-8.2 vs 66.8+/-9.3, P<0.05), but not to gender or site of the tumor. CONCLUSION: IPMN is associated with a high incidence of other malignancies, particularly gastric and colonic cancers. Common genetic mechanisms between IPMN and other associated malignancies might be present. Clinicians should pay attention to the possibility of associated malignancies in preoperative screening and follow-up of patients with IPMN.

Thermo-chemo-radiotherapy for advanced bile duct carcinoma.

AIM: Complete resection of the bile duct carcinoma is sometimes difficult by subepithelial spread in the duct wall or direct invasion of adjacent blood vessels. Nonresected extrahepatic bile duct carcinoma has a dismal prognosis, with a life expectancy of about 6 mo to 1 year. To improve the treatment results of locally advanced bile duct carcinoma, we have been conducting a clinical trial using regional hyperthermia in combination with chemoradiation therapy. METHODS: Eight patients complaining of obstructive jaundice with advanced extrahepatic bile duct underwent thermo-chemo-radiotherapy (TCRT). All tumors were located in the upper bile duct and involved hepatic bifurcation, and obstructed the bile duct completely. Radiofrequency capacitive hyperthermia was administered simultaneously with chemotherapeutic agents once weekly immediately following radiotherapy at 2 Gy. We administered heat to the patient for 40 min after the tumor temperature had risen to 42 degrees C. The chemotherapeutic agents employed were cis-platinum (CDDP, 50 mg/m(2)) in combination with 5-fluorouracil (5-FU, 800 mg/m(2)) or methotrexate (MTX, 30 mg/m(2)) in combination with 5-FU (800 mg/m(2)). Number of heat treatments ranged from 2 to 8 sessions. The bile duct at autopsy was histologically examined in three patients treated with TCRT. RESULTS: In respect to resolution of the bile duct, there were three complete regression (CR), two partial regression (PR), and three no change (NC). Mean survival was 13.2+/-10.8 mo (mean+/-SD). Four patients survived for more than 20 mo. Percutaneous transhepatic biliary drainage (PTBD) tube could be removed in placement of self-expandable metallic stent into the patency-restored bile duct after TCRT. No major side effects occurred. At autopsy, marked hyalinization or fibrosis with necrosis replaced extensively bile duct tumor and wall, in which suppressed cohesiveness of carcinoma cells and degenerative cells were sparsely observed. CONCLUSION: Although the number of cases is rather small, TCRT in the treatment of locally advanced bile duct carcinoma is promising in raising local control and thus, long-term survival.