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table S1 : recombination detection primers and qPCR primers. tableS2 : antibodies for immunohistochemistory and two chamber assay. tableS3 : list of PDAC patients

Supplemental Table 1. PanNETs incidence per genotype. Figure S1: Representative images of LacZ staining in the pancreas in Pdx1-Cre;Rosa26R mice; S2: Experimental strategy for generation of Pdx1-Cre;Trp53R172H mice. S3: H&E, immunohistochemical and immunofluorescence staining of islet cells in Pdx1-Cre and Pdx1-Cre;Trp53R172H;Rbf/f mice at 2 months of age.

Histological analysis of ICC and the incidence of HCC developed in AlbcreKP; RosaNotchOE and AlbcreKP; RosaNotchOE; Hes1flox/flox mice at 8 weeks of age.

Myofibroblasts secrete Cola 1a1 and Cxcl12 in tumor environment.

Leading edge genes in gene set enrichment analysys using HALLMARK gene set of KRAS_SIGNALING_UP.

Intrahepatic cholangiocarcinoma (ICC) is frequently driven by aberrant KRAS activation and develops in the liver with chronic inflammation. Although the Notch signaling pathway is critically involved in ICC development, detailed mechanisms of Notch-driven ICC development are still unknown. Here, we use mice whose Notch signaling is genetically engineered to show that the Notch signaling pathway, specifically the Notch/Hes1 axis, plays an essential role in expanding ductular cells in the liver with chronic inflammation or oncogenic Kras activation. Activation of Notch1 enhanced the development of proliferating ductal cells (PDC) in injured livers, while depletion of Hes1 led to suppression. In correlation with PDC expansion, ICC development was also regulated by the Notch/Hes1 axis and suppressed by Hes1 depletion. Lineage-tracing experiments using EpcamcreERT2 mice further confirmed that Hes1 plays a critical role in the induction of PDC and that ICC could originate from PDC. Analysis of human ICC specimens showed PDC in nonneoplastic background tissues, confirming HES1 expression in both PDC and ICC tumor cells. Our findings provide novel direct experimental evidence that Hes1 plays an essential role in the development of ICC via PDC.Significance:This study contributes to the identification of the cells of origin that initiate ICC and suggests that HES1 may represent a therapeutic target in ICC.

Pancreatic neuroendocrine tumors (PanNET) were classified into grades (G) 1 to 3 by the World Health Organization in 2017, but the precise mechanisms of PanNET initiation and progression have remained unclear. In this study, we used a genetically engineered mouse model to investigate the mechanisms of PanNET formation. Although pancreas-specific deletion of the Rb gene (Pdx1-Cre;Rbf/f) in mice did not affect pancreatic exocrine cells, the α-cell/β-cell ratio of islet cells was decreased at 8 months of age. During long-term observation (18–20 months), mice formed well-differentiated PanNET with a Ki67-labeling index of 2.7%. In contrast, pancreas-specific induction of a p53 mutation (Pdx1-Cre;Trp53R172H) had no effect on pancreatic exocrine and endocrine tissues, but simultaneous induction of a p53 mutation with Rb gene deletion (Pdx1-Cre;Trp53R172H;Rb f/f) resulted in the formation of aggressive PanNET with a Ki67-labeling index of 24.7% over the short-term (4 months). In Pdx1-Cre;Trp53R172H;Rbf/f mice, mRNA expression of Pten and Tsc2, negative regulators of the mTOR pathway, significantly decreased in the islet cells, and activation of the mTOR pathway was confirmed in subsequently formed PanNET. Thus, by manipulating Rb and p53 genes, we established a multistep progression model from dysplastic islet to indolent PanNET and aggressive metastatic PanNET in mice. These observations suggest that Rb and p53 have distinct roles in the development of PanNET.Significance:Pancreas-specific manipulation of Rb and p53 genes induced malignant transformation of islet cells, reproducing stepwise progression from microadenomas to indolent (grade 1) and subsequent aggressive PanNETs (grade 2–3).

Supplemental Data

Supplemental Figure legends and Table Legend

Material and Methods of Whole exome sequencing.

Supplemental References

Supplementary Figure S3. RNAseq data sets derived from The Cancer Genome Atlas (TCGA) showed various levels of AID mRNA expression in human pancreatic adenocarcinomas (N: Number). In addition, AID mRNA expression level in human pancreatic adenocarcinoma was higher than the mean AID mRNA expression level in all cancer types.

Primers of murine DNA deep sequencing analysis.

Supplemental Figure Legend

Notch/Hes1 signaling has been shown to play a role in determining the fate of pancreatic progenitor cells. However, its function in postnatal pancreatic maturation is not fully elucidated. We generated conditional Hes1 knockout and/or Notch intracellular domain (NICD) overexpression mice in Ptf1a- or Pdx1-positive pancreatic progenitor cells and analyzed pancreatic tissues. Both Ptf1acre/+; Hes1f/f and Ptf1acre/+; Rosa26NICD mice showed normal pancreatic development at P0. However, exocrine tissue of the pancreatic tail in Ptf1acre/+; Hes1f/f mice atrophied and was replaced by fat tissue by 4 weeks of age, with increased apoptotic cells and fewer centroacinar cells. This impaired exocrine development was completely rescued by NICD overexpression in Ptf1acre/+; Hes1f/f; Rosa26NICD mice, suggesting compensation by a Notch signaling pathway other than Hes1. Conversely, Pdx1-Cre; Hes1f/f mice showed impaired postnatal exocrine development in both the pancreatic head and tail, revealing that the timing and distribution of embryonic Hes1 expression affects postnatal exocrine tissue development. Notch signaling has an essential role in pancreatic progenitor cells for the postnatal maturation of exocrine tissue, partly through the formation of centroacinar cells.

Intrahepatic cholangiocarcinoma (ICC) is frequently driven by aberrant KRAS activation and develops in the liver with chronic inflammation. Although the Notch signaling pathway is critically involved in ICC development, detailed mechanisms of Notch-driven ICC development are still unknown. Here, we use mice whose Notch signaling is genetically engineered to show that the Notch signaling pathway, specifically the Notch/Hes1 axis, plays an essential role in expanding ductular cells in the liver with chronic inflammation or oncogenic Kras activation. Activation of Notch1 enhanced the development of proliferating ductal cells (PDC) in injured livers, while depletion of Hes1 led to suppression. In correlation with PDC expansion, ICC development was also regulated by the Notch/Hes1 axis and suppressed by Hes1 depletion. Lineage-tracing experiments using EpcamcreERT2 mice further confirmed that Hes1 plays a critical role in the induction of PDC and that ICC could originate from PDC. Analysis of human ICC specimens showed PDC in nonneoplastic background tissues, confirming HES1 expression in both PDC and ICC tumor cells. Our findings provide novel direct experimental evidence that Hes1 plays an essential role in the development of ICC via PDC. Significance: This study contributes to the identification of the cells of origin that initiate ICC and suggests that HES1 may represent a therapeutic target in ICC.

In the original version of [this article][1] ([1][2]), there were typographical errors in the Results sections describing the data presented in Figs. 2A, 3E, and 3K–3S. Likewise, the incorrect statistical analysis was indicated in the legend for Fig. 4D and E. The authors have revised the text to

Most pancreatic ductal adenocarcinoma (PDAC) develops from pancreatic epithelial cells bearing activating mutant KRAS genes through precancerous lesions, i.e. acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). During pancreatic tumorigenesis, Hes1 expression starts with the transition from acinar cells to ADM, and continues during PanIN and PDAC formation, but the role of Hes1 in pancreatic tumorigenesis is not fully elucidated. Here we show that Hes1 plays an essential role in the initiation and progression of KRAS-driven pancreatic tumorigenesis. In vitro, activation of MAPK signaling due to EGF or mutant KRAS activation induced sustained Hes1 expression in pancreatic acinar cells. In vivo, acinar cell-specific activation of mutant KRAS by Elastase1-CreERT2;KrasG12D induced ADM/PanIN formation with Hes1 expression in mice, and genetic ablation of Hes1 in these mice dramatically suppressed PanIN formation. Gene expression analysis and lineage tracing revealed that Hes1 regulates acinar-to-ductal reprogramming-related genes and, in a Hes1-deficient state, mutant Kras-induced ADM could not progress into PanIN, but re-differentiated into acinar cells. In the Elastase1-CreERT2;KrasG12D;Trp53R172H mouse PDAC model, genetic ablation of Hes1 completely blocked PDAC formation by keeping PanIN lesions in low-grade conditions, in addition to reducing the occurrence of PanIN. Together, these findings indicate that mutant KRAS-induced Hes1 plays an essential role in PDAC initiation and progression by regulating acinar-to-ductal reprogramming-related genes.

Notch/Hes1 signaling has been shown to play a role in determining the fate of pancreatic progenitor cells. However, its function in postnatal pancreatic maturation is not fully elucidated.We generated conditional Hes1 knockout and/or Notch intracellular domain (NICD) overexpression mice in Ptf1a- or Pdx1-positive pancreatic progenitor cells and analyzed pancreatic tissues.Both Ptf1aNotch signaling has an essential role in pancreatic progenitor cells for the postnatal maturation of exocrine tissue, partly through the formation of centroacinar cells.

Pancreatic neuroendocrine tumors (PanNET) were classified into grades (G) 1 to 3 by the World Health Organization in 2017, but the precise mechanisms of PanNET initiation and progression have remained unclear. In this study, we used a genetically engineered mouse model to investigate the mechanisms of PanNET formation. Although pancreas-specific deletion of the Rb gene (Pdx1-Cre;Rbf/f) in mice did not affect pancreatic exocrine cells, the α-cell/β-cell ratio of islet cells was decreased at 8 months of age. During long-term observation (18–20 months), mice formed well-differentiated PanNET with a Ki67-labeling index of 2.7%. In contrast, pancreas-specific induction of a p53 mutation (Pdx1-Cre;Trp53R172H) had no effect on pancreatic exocrine and endocrine tissues, but simultaneous induction of a p53 mutation with Rb gene deletion (Pdx1-Cre;Trp53R172H;Rb f/f) resulted in the formation of aggressive PanNET with a Ki67-labeling index of 24.7% over the short-term (4 months). In Pdx1-Cre;Trp53R172H;Rbf/f mice, mRNA expression of Pten and Tsc2, negative regulators of the mTOR pathway, significantly decreased in the islet cells, and activation of the mTOR pathway was confirmed in subsequently formed PanNET. Thus, by manipulating Rb and p53 genes, we established a multistep progression model from dysplastic islet to indolent PanNET and aggressive metastatic PanNET in mice. These observations suggest that Rb and p53 have distinct roles in the development of PanNET. Significance: Pancreas-specific manipulation of Rb and p53 genes induced malignant transformation of islet cells, reproducing stepwise progression from microadenomas to indolent (grade 1) and subsequent aggressive PanNETs (grade 2–3).

Minor and trace metals in aluminum and aluminum alloys have been determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) as an interlaboratory testing toward standardization. The trueness of the measured data was successfully investigated to improve the analytical protocols, using certified reference materials of aluminum. Their precision could also be evaluated, feasible to estimate the uncertainties separately. The accuracy (trueness and precision) of the data were finally in good agreement with the certified values and assigned uncertainties. Repeated measurements of aluminum solutions with different concentrations of the analytes revealed the relative standard deviations of the measurements with concentrations, thus enabling their limits of quantitation. They differed separately and also showed slightly higher values with an aluminum matrix than those without one. In addition, the upper limit of the detectable concentration of silicon with simple acid digestion was estimated to be 0.03 % in the mass fraction.

Although simultaneous occurrences of autoimmune pancreatitis (AIP) and cancer are occasionally observed, it remains largely unknown whether cancer and AIP occur independently or these disorders are interrelated. The aim of this study was to examine the relationship between AIP and cancer.We conducted a multicenter, retrospective cohort study. One hundred and eight patients who met the Asian diagnostic criteria for AIP were included in the study. We calculated the proportion, standardized incidence ratio (SIR), relative risk, and time course of cancer development in patients with AIP. We also analyzed the clinicopathological characteristics of AIP patients with cancer in comparison with those without cancer.Of the 108 AIP patients, 18 cancers were found in 15 patients (13.9%) during the median follow-up period of 3.3 years. The SIR of cancer was 2.7 (95% confidence interval (CI) 1.4-3.9), which was stratified into the first year (6.1 (95% CI 2.3-9.9)) and subsequent years (1.5 (95% CI 0.3-2.8)) after AIP diagnosis. Relative risk of cancer among AIP patients at the time of AIP diagnosis was 4.9 (95% CI 1.7-14.9). In six of eight patients whose cancer lesions could be assessed before corticosteroid therapy for AIP, abundant IgG4-positive plasma cell infiltration was observed in the cancer stroma. These six patients experienced no AIP relapse after successful cancer treatment.Patients with AIP are at high risk of having various cancers. The highest risk for cancer in the first year after AIP diagnosis and absence of AIP relapse after successful treatment of the coexisting cancers suggest that AIP may develop as a paraneoplastic syndrome in some patients.

Objective: Pancreatic fistula (PF) is an early complication after pancreatoduodenectomy. PF occurs because of disruption to the pancreatodigestive tract anastomosis with stricture or occlusion. A strategy to treat PF using interventional methods is proposed. Methods: We treated a total of 6 patients with PF by endoscopic ultrasound (EUS)-guided or percutaneous pancreatic duct drainage. In this paper, these patients are reviewed based on the applied treatment for PF. Results: At the time of introduction to our department, all the patients, except for one, had a percutaneous drainage tube implanted prior to surgery. In 2 patients undergoing pancreatojejunostomy within 3 months of the previous surgery, percutaneous introduction of a guidewire into the anastomosed jejunum, via the disrupted anastomosis, through the percutaneous fistula and the implantation of a percutaneous jejunal tube for 6 weeks was an effective PF treatment. There were 4 patients (3 pancreatojejunostomy, 1 pancreatogastrostomy) with more than 3 months of PF, with an occluded anastomosis and the pancreatic juice flow had to be rerouted by making another pancreatodigestive tract anastomosis using percutaneous or EUS-guided puncture of the pancreatic duct. Conclusions: The optimal treatment for PF is considered to be the recanalization of the stricture or occluded anastomosis, or rerouting of the pancreatic juice flow by making another anastomosis. Considering our experiences in the treatment of PF, EUS-guided puncture of the pancreatic duct near the occluded anastomosis using a convex-type EUS endoscopy is the most preferable method to treat PF. In patients for whom it is difficult to introduce the endoscope into the afferent loop in the pancreatojejunostomy, various methods, including percutaneous approaches, are feasible to treat PF.

Background Pancreatodigestive tract anastomotic site stenosis is a problematic complication after pancreatoduodenectomy. Objective We evaluated the feasibility and efficacy of endoscopic treatments for a stenotic pancreatodigestive tract anastomosis. Design Retrospective study. Setting Endoscopic units of a university-affiliated hospital and a general hospital. Patients Fourteen patients with recurrent pancreatitis (n = 10) and pancreatic fluid fistula (n = 4) after anatomy-altering surgery with pancreatodigestive tract anastomosis. Interventions The initial ERCP included obtaining a pancreatogram, introducing a 0.025-inch guidewire through the anastomosis, along which a 5F plastic stent or nasopancreatic drain was inserted. If initial ERCP failed, we attempted EUS-guided rendezvous, with a guidewire passed antegrade from the main pancreatic duct across the stenotic anastomosis. Main Outcome Measurements Rates of successful intervention and clinical relief. Results The initial intervention was successfully achieved in 6 of 14 patients (38%). Of the 6 patients with successful therapeutic endoscopies, 4 (66.7%) and 2 (25.0%) had undergone a previous pancreatogastrostomy or pancreatojejunostomy, respectively. Eight patients with an initial unsuccessful intervention successfully underwent a second intervention using an EUS-guided or US-guided rendezvous method. Finally, stenosis was relieved in all patients with either the retrograde placement of a pancreatic duct stent across the stenosis of an anastomotic site or antegrade percutaneous bougienage of the stenotic anastomosis. Limitations Small sample size and lack of control patients. Conclusions Endoscopic treatment of stenotic pancreatodigestive tract anastomosis for transanastomotic pancreatic juice drainage is safe and feasible.

Stenotic pancreatico-enteric anastomosis is one of the serious late complications after a pancreaticoduodenectomy. We report a case of stenotic pancreaticojejunostomy with a pancreatic juice fistula drained externally, which was treated using percutaneous procedures combined with a rendezvous method. A 77-year-old woman was referred to our hospital for an endoscopic treatment to remove a percutaneous drainage tube from a fluid collection due to pancreatic juice fistula. She had undergone pylorus-preserving pancreatoduodenectomy with Roux-en-Y reconstruction due to duodenal carcinoma of Vater's papilla 1 year before the referral to our hospital. Soon after the operation, she had developed a fluid collection adjacent to the anastomosis due to pancreatic juice fistulas and subsequently had undergone its percutaneous drainage. After admission, we tried to dilate the stenotic anastomosis with an endoscopic procedure from the anastomosed jejunal lumen, using an oblique-viewing endoscope. The endoscope reached a portion of the anastomosis, but did not allow us to visualize the entire anastomosis. We punctured the main pancreatic duct under ultrasonography and fluoroscopy, and advanced the needle into the anastomosed jejunum through the stenotic anastomosis. After putting a guidewire into the anastomosed jejunum through the needle, we introduced an oblique-viewing endoscope into the anastomosed jejunum and caught hold of the guidewire using grasping forceps. Maintaining tension on the guidewire with a slight pulling force, with some effort we were able to place a 5-Fr drainage catheter into the jejunum percutaneously and through the anastomosis via the main pancreatic duct. Three weeks after these procedures, we performed balloon dilation of the anastomosis. One week after balloon dilation, removed the percutaneous catheter.

Three-dimensional (3D) photonic crystals can block photons in any direction and are expected to make possible their ultimate control. However, creating 3D crystals without any unintentional defects over large areas at optical wavelengths has been challenging. For example, opal-based crystals inevitably contain unintentional defects, it is difficult to increase the sizes of micro-manipulated crystals over approximately 6 microm and producing stacked 3D crystals with thin 2D layers requires complicated and time-consuming processes. So far, these difficulties have hindered 3D photonic-crystal research. Here, we demonstrate a novel top-down approach to creating 3D crystals that overcomes these difficulties and significantly simplifies the process. We have developed a double-angled deep-etching method, which enables the direct creation of 3D woodpile crystals in single-crystalline silicon. A strong photonic bandgap effect with >20 dB attenuation in all directions has been achieved. Furthermore, bonding a light emitter onto or between 3D crystals created in this way has been shown to enhance or suppress spontaneous emission.

A 46-year-old female patient was referred to our hospital for endoscopic treatment of stenotic pancreatogastrostomy. She had undergone pylorus-preserving pancreatoduodenectomy due to duodenal carcinoma of the papilla of Vater 5 years before referral. Two years after the operation, she had to be hospitalized several times during a 1-year period because of acute recurrent pancreatitis caused by stenosis of the anastomosis of the pancreatoduodenostomy. An endoscopic ultrasound (EUS)-guided rendezvous technique was selected to puncture the main pancreatic duct via a transgastric approach. We identified the dilated main pancreatic duct with a convex array echoendoscope from the lower gastric body near the anastomosis and successfully punctured the dilated main pancreatic duct. The guidewire passed through the stenosis to the gastric cavity and we could place a stent through the stenotic anastomosis. After the procedure, the patient has not experienced acute recurrent pancreatitis for 9 months. Pancreatogastrostomy has been the preferred method used to carry out post-pancreatoduodenectomy reconstruction. However, stenosis of the anastomosis has been reported as one of the late complications of pancreatogastrostomy. The main symptom of this complication is recurrent epigastralgia due to obstructive pancreatitis. As a result, patients are compelled to stay in the hospital for an extended duration with no oral intake allowed. Surgical resection of the stenosis is often the treatment of choice but can be troublesome due to post-operative adhesions. Here, we report a case of pancreatogastrostomy complicated by stenosis, which was treated using the EUS-guided rendezvous technique.

We improved the satellite-based empirical model (Kitamoto et al., 2007) by adding additional effective parameters on vapor pressure deficit (VPD) and photosynthesis, and estimated the CO2 budget within black spruce forests in Alaska. In the stand scale validation, our modified model successfully reproduced the observed gross primary productivity (GPP), ecosystem respiration (RE), and net ecosystem exchange (NEE) by the eddy covariance measurement. The 10-day average of the model output was highly correlated with the observed GPP (r2=0.9), RE (r2=0.9), and NEE (r2=0.7).We used the modified model to estimate the regional GPP, RE, and NEE of black spruce forests over Alaska from 1982 to 2003 by using the normalized difference vegetation index (NDVI) from the Advanced Very High Resolution Radiometer (AVHRR) and climate data. The estimated regional averages of GPP, RE, and NEE were 2,172, 2,008, and -164 g CO2 m-2 y-1 during the past 22 years. Our model analysis showed that GPP was mainly affected by spring air temperature, whereas RE was affected by summer air temperature, indicating that the sink strength of the black spruce forests was controlled by the seasonality in air temperature between spring and summer. Path analysis enforced the notation that spring warming increased the CO2 sink, but summer warming decreased the sink.

Objective IgG4-related disease (IgG4-RD) is a systemic disease characterised by elevated serum IgG4 and IgG4-positive lymphoplasmacytic infiltration in the affected tissues. The pathogenic role of IgGs, including IgG4, in patients with IgG4-RD, however, is unknown. Design We examined the pathogenic activity of circulating IgGs in patients with IgG4-RD by injecting their IgGs into neonatal male Balb/c mice. Binding of patient IgGs to pancreatic tissue was also analysed in an ex vivo mouse organ culture model and in tissue samples from patients with autoimmune pancreatitis (AIP). Results Subcutaneous injection of patient IgG, but not control IgG, resulted in pancreatic and salivary gland injuries. Pancreatic injury was also induced by injecting patient IgG1 or IgG4, with more destructive changes induced by IgG1 than by IgG4. The potent pathogenic activity of patient IgG1 was significantly inhibited by simultaneous injection of patient IgG4. Binding of patient IgG, especially IgG1 and IgG4, to pancreatic tissue was confirmed in both the mouse model and AIP tissue samples. Conclusions IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding affected tissues in neonatal mice.

This study proposes a method for identifying poor visibility under adverse weather conditions by processing closed-circuit television (CCTV) digital images. The weighted intensity of the power spectrum (WIPS) was examined to determine its applicability as a value for the identification of poor visibility. The magnitude of WIPS represents the difference in spatial frequencies within the image on the basis of the human contrast sensitivity function. WIPS was calculated by the following image-processing procedure: the spatial frequency of the cutout image was calculated with a two-dimensional Fourier transform, and the power spectrum of the cutout image was calculated; WIPS was totaled at spatial frequencies that ranged from 1.5 to 18 cycles per degree. Two kinds of experiments were performed to determine whether WIPS represented the subjective visibility assessment values (SVAVs) given by the test subjects. Clear linear relationships between WIPS and SVAVs were found in both experiments. In addition, the two correlation lines overlapped within the whole range of WIPS. These results suggest that WIPS may be appropriate for identifying poor visibility by the use of digital images.

Pancreatic ductal adenocarcinoma (PDAC) develops via an accumulation of various gene mutations. The mechanism underlying the mutations in PDAC development, however, is not fully understood. Recent insight into the close association between the mutation pattern of various cancers and specific mutagens led us to investigate the possible involvement of activation-induced cytidine deaminase (AID), a DNA editing enzyme, in pancreatic tumorigenesis. Our immunohistochemical findings revealed AID protein expression in human acinar ductal metaplasia, pancreatic intraepithelial neoplasia, and PDAC. Both the amount and intensity of the AID protein expression increased with the progression from precancerous to cancerous lesions in human PDAC tissues. To further assess the significance of ectopic epithelial AID expression in pancreatic tumorigenesis, we analyzed the phenotype of AID transgenic (AID Tg) mice. Consistent with our hypothesis that AID is involved in the mechanism of the mutations underlying pancreatic tumorigenesis, we found precancerous lesions developing in the pancreas of AID Tg mice. Using deep sequencing, we also detected Kras and c-Myc mutations in our analysis of the whole pancreas of AID Tg mice. In addition, Sanger sequencing confirmed the presence of Kras, c-Myc, and Smad4 mutations, with the typical mutational footprint of AID in precancerous lesions in AID Tg mice separated by laser capture microdissection. Taken together, our findings suggest that AID contributes to the development of pancreatic precancerous lesions by inducing tumor-related gene mutations. Our new mouse model without intentional manipulation of specific tumor-related genes provides a powerful system for analyzing the mutations involved in PDAC. Cancer Res; 75(16); 3292–301. ©2015 AACR.

We investigated the capability of a cavity resonator to obtain the mapping of the microwave conductivity for the strongly correlated materials showing the phase separation near the metal-insulator transition. As shown in Figs. 1(a) and 1(b), a metallic tip mounted on a rod along a cylindrical axis (z axis) of the cavity resonator concentrates the microwave electric field, E, operated at TM010 mode on a point of a sample inserted into the cavity [1]. Thus, by moving the sample on a plane perpendicular to the z axis, the local microwave properties of the sample can be measured as a function of the location on the sample. Experimental results which were obtained at room temperature by using a home-made reference sample strongly suggest that the conductive or dielectric part in the reference sample can be clearly detected by the change of the resonance frequency, as shown in Fig. 1(c).

We design and demonstrate nanocavities with TE-like and TM-like polarizations at the surface of 3D photonic crystals using 3D design freedom in a 3D structure and the polarization-independent surface-mode gap.

A case of apocrine carcinoma of the breast developed in a cystic form is described herein. Apocrine carcinoma is rare, especially cystic apocrine carcinoma in this case. The case involved a 40 year old Japanese woman. Morphologically, the tumor developed circularly inside of the thick capsule and histologically, both the carcinoma and non-cancerous mammary tissue showed marked apocrine meta-plasia. The analysis of nuclear DNA content by flow cytometry showed intratumoral variations in DNA distribution pattern. Radical mastectomy was performed. The excised tumor was 3.5×3.0cm in size and t2n0M0 in stage II. No lymph node metastasis was seen. There has been no sign of recurrence, as of two years and 5 months after the operation. The present case is very interesting in discussining the relationship between the carcinoma and apocrine metaplasia, morphologically and histologically.

Stenotic pancreatico-enteric anastomosis is one of the serious late complications after a pancreaticoduodenectomy. We report a case of stenotic pancreaticojejunostomy with a pancreatic juice fistula drained externally, which was treated using percutaneous procedures combined with a rendezvous method. A 77-year-old woman was referred to our hospital for an endoscopic treatment to remove a percutaneous drainage tube from a fluid collection due to pancreatic juice fistula. She had undergone pylorus-preserving pancreatoduodenectomy with Roux-en-Y reconstruction due to duodenal carcinoma of Vater's papilla 1 year before the referral to our hospital. Soon after the operation, she had developed a fluid collection adjacent to the anastomosis due to pancreatic juice fistulas and subsequently had undergone its percutaneous drainage. After admission, we tried to dilate the stenotic anastomosis with an endoscopic procedure from the anastomosed jejunal lumen, using an oblique-viewing endoscope. The endoscope reached a portion of the anastomosis, but did not allow us to visualize the entire anastomosis. We punctured the main pancreatic duct under ultrasonography and fluoroscopy, and advanced the needle into the anastomosed jejunum through the stenotic anastomosis. After putting a guidewire into the anastomosed jejunum through the needle, we introduced an oblique-viewing endoscope into the anastomosed jejunum and caught hold of the guidewire using grasping forceps. Maintaining tension on the guidewire with a slight pulling force, with some effort we were able to place a 5-Fr drainage catheter into the jejunum percutaneously and through the anastomosis via the main pancreatic duct. Three weeks after these procedures, we performed balloon dilation of the anastomosis. One week after balloon dilation, removed the percutaneous catheter.

Chronic pancreatitis (CP) is a progressive inflammatory disease that eventually results in the impairment of exocrine and endocrine functions of the pancreas. Recent studies have shown an association between mutations in the serine protease inhibitor Kazal type 1 (SPINK1) gene and CP. SPINK1 provides the first line of defense against prematurely activated trypsinogen by physically blocking the active site of trypsin. The IVS3+2T>C (c.194+2T>C) mutation is a loss-of-function splicing mutation; it affects the consensus splicing donor site in intron 3 and may cause the skipping of the entire exon 3, where the trypsin-binding site is located. We report here three CP patients carrying this mutation in a homozygous form, with no noticeable family history of pancreatitis. The first patient is a 25-year-old male with juvenile-onset idiopathic CP. He suffered from repeated attacks of pancreatitis since 5 years old and underwent pancreatico-jejunostomy. He complained of epigastralgia, and was diagnosed as obstructive pancreatitis in the area of the accessory pancreatic duct. The second patient is a 75-year-old male with alcoholic CP. He did not have apparent attacks of pancreatitis, but had numerous calcifications throughout the pancreas and confirmed exocrine failure and diabetes mellitus. The last patient is a 44-year-old female with late-onset idiopathic CP. She suffered from repeated attacks of pancreatitis since 32 years old. She had numerous stones in the main pancreatic duct in the pancreas head and confirmed exocrine failure. The clinical courses of these patients are apparently different, indicating the phenotypic variability of the SPINK1 IVS3+2T>C mutation-associated CP.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients after Billroth II or Roux-en-Y reconstruction is challenging because of difficulties in insertion of the endoscope into the afferent loop, which is a great distance away from the papilla of Vater, and cannulation into the desired duct from a reverse position. To facilitate ERCP, various endoscopes have been selected according to operator preference. Previously, we reported that an oblique-viewing endoscope (XK-200; Olympus, Tokyo, Japan) can contribute to successful performance of ERCP and associated procedures in Billroth II gastrectomy patients. We report here our experience with two post-gastrectomy patients with chronic pancreatitis who were treated with an oblique-viewing endoscope from the minor papilla.

A 34-year-old woman was admitted because of severe liver dysfunction due to excessive alcohol intake. Liver biopsy performed on the fifth day showed liver tissue with marked granulocyte infiltration and pericellular fibrosis. As there were no improvements in white blood cell count and serum total bilirubin levels despite the use of corticosteroids and plasma exchange, hemodiafiltration, we performed granulocytapheresis (GCAP). Peripheral white blood cells decreased from just after GCAP. Her condition remained stable and she was discharged on the 54th day. We suggest that GCAP can be recommended as an effective therapy for severe alcoholic hepatitis.

Three-dimensional photonic crystals are successfully fabricated by a double-angled deep-etching technique. Furthermore, bonding a light emitter onto or between three-dimensional crystals has been shown to enhance or suppress emission.

Background: We report that an oblique-viewing endoscope facilitates endoscopic retrograde cholangiopancreatography (ERCP) in Billroth II reconstruction. With this endoscope, we carried out ERCP in Roux-en-Y reconstruction. Methods: Fifteen patients with Roux-en-Y reconstruction were enrolled. Eleven of these patients had undergone gastrectomy, while Whipple's operation or choledochectomy had each been carried out in two patients. Among the 11 post-gastrectomy patients, eight had bile duct stones, and there was one case each of pancreatic abscess with chronic pancreatitis, bile duct obstruction due to gallbladder, or pancreatic cancer. The remaining four patients suffered from stenotic anastomosis of choledochojejunostomy. All procedures were carried out with an oblique-viewing endoscope. Results: The papilla of Vater or anastomosis was reached in 10 patients. In these 10 patients, all planned procedures were completed. Endoscopic papillary balloon dilatation (EPBD) was carried out in three patients with bile duct stones. The remaining three patients with bile duct stones underwent sphincterotomy with tube stent placement, EPBD after sphincterotomy with biliary tube stent placement, and biliary tube stent placement, respectively. Pancreatic stent placement via the minor papilla was carried out in one patient with pancreatic abscess, and a biliary tube stent was introduced in the patient with gallbladder cancer. Two patients underwent cutting of a stenotic anastomosis with a needle knife, followed by balloon dilatation. None of the patients experienced any complications. Conclusion: The results appear to support the feasibility of using an oblique-viewing endoscope for ERCP in Roux-en-Y reconstruction. Further studies including a large population of patients should be planned to confirm these results.