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e21007Background: Overexpression of PD-L1 is associated with better clinical responses to PD-1/PD-L1 blockade in melanoma, but the utility of PD-L1 immunostaining as a predictive biomarker for anti...

Laparoscopic surgery has been widely accepted as a feasible and safe treatment modality in many cancers of the gastrointestinal tract. However, most guidelines on gallbladder cancer (GBC) regard laparoscopic surgery as a contraindication, even for early GBC. This study aims to evaluate and compare recent surgical outcomes of laparoscopic and open surgery for T1(a,b) GBC and to determine the optimal surgical strategy for T1 GBC. The study enrolled 197 patients with histopathologically proven T1 GBC and no history of other cancers who underwent surgery from 2000 to 2014 at 3 major tertiary referral hospitals with specialized biliary-pancreas pathologists and optimal pathologic handling protocols. Median follow-up was 56 months. The effects of depth of invasion and type of surgery on disease-specific survival and recurrence patterns were investigated. Of the 197 patients, 116 (58.9%) underwent simple cholecystectomy, including 31 (15.7%) who underwent open cholecystectomy and 85 (43.1%) laparoscopic cholecystectomy. The remaining 81 (41.1%) patients underwent extended cholecystectomy. Five-year disease-specific survival rates were similar in patients who underwent simple and extended cholecystectomy (96.7% vs 100%, P = 0.483), as well as being similar in patients in the simple cholecystectomy group who underwent open and laparoscopic cholecystectomy (100% vs 97.6%, P = 0.543). Type of surgery had no effect on recurrence patterns. Laparoscopic cholecystectomy for T1 gallbladder cancer can provide similar survival outcomes compared to open surgery. Considering less blood loss and shorter hospital stay with better cosmetic outcome, laparoscopic cholecystectomy can be justified as a standard treatment for T1b as well as T1a gallbladder cancer when done by well-experienced surgeons based on exact pathologic diagnosis.

Summary β-catenin plays an important role in hair morphogenesis. Previously, the nuclear and cytoplasmic localizations of β-catenin were identified in hair-matrix cells. To evaluate β-catenin expression in the nail matrix, we obtained human nail units. Immunohistochemistry for β-catenin was used to evaluate sections of normal nail units and of sections from a single case of onychomatricoma. In the nail unit, β-catenin was expressed in the nucleus and cytoplasm of the suprabasal nail-matrix cells. Of the other epithelial-cell types, only the cell membrane was β-catenin-positive. In the nail tissue from the onychomatricoma case, β-catenin was expressed in the nucleus and cytoplasm of the upper epithelial layers. Our result suggests that β-catenin plays an important role in nail formation. In addition, β-catenin expression in onychomatricoma supports the presence of nail-matrix cells in this condition. To our knowledge, this is the first report of β-catenin expression in the nucleus and cytoplasm of the nail matrix.

Background The purpose of this study was to identify management strategies for non-functioning pancreatic neuroendocrine tumours (NF-PNETs) by analysis of surgical outcomes at a single institution. Methods Archived records of patients with NF-PNETs who underwent surgery between 1994 and 2010 were reviewed. Results Among 125 patients, the median tumour size was 2·5 (range 0·15–20·5) cm. Of the 51 NF-PNETs with a diameter of no more than 2 cm, 12 (24 per cent) were diagnosed as carcinoma. Overall 20 patients (16·0 per cent) had metastases to the lymph nodes. The minimum size of the tumour with lymph node metastasis was 1·2 cm. Having a NF-PNET of 2 cm or larger significantly increased the probability of a poorly differentiated carcinoma (P = 0·006), and having a NF-PNET of at least 2·5 cm significantly increased the probability of lymph node metastasis (P = 0·048). The 5-year cumulative survival rate after curative resection was 89·7 per cent. During a median follow-up of 31·5 months, there were 27 recurrences (23·1 per cent) and 13 disease-specific deaths (11·1 per cent) among the 117 patients who had an R0 resection. All patients who underwent repeat operations were alive without additional recurrence after a mean(s.d.) follow-up of 27·1(18·0) months. Conclusion Curative surgery should be performed for control of primary NF-PNETs. Lymph node dissection for NF-PNETs of 2·5 cm or larger and at least node sampling for tumours with a diameter of 1 cm or more are recommended. Debulking surgery should be considered for advanced tumours.

Neuroendocrine tumor (NET) in adenoma of the gastrointestinal tract is a rare mixed glandular-endocrine neoplasm and has uncommonly been described mostly in the colon. Histologically, this tumor is composed of a predominant proportion of benign adenomatous component and a small portion of well-differentiated NE component. Only three cases of NET in gastric adenoma have been reported in the literature. We present 4 cases of NET in gastric adenoma mimicking invasive adenocarcinoma. The NETs were 0.62 mm to 4.1 mm in size and located at the basal lamina propria, muscularis mucosa and submucosa. Histologically, NETs consisted of nests, cords, tubules, and clusters of cells that predominantly interposed between the foveolar base without disturbing the overall polyp architecture. The lesions were completely removed by endoscopic submucosal dissection in three cases and in one case, subtotal gastrectomy was performed because endoscopic biopsy was invasive adenocarcinoma. The patients’ clinical course was uneventful without an evidence of recurrence or metastasis. The recognition of NET in gastric adenoma will help avoid potential diagnostic pitfalls masquerading as invasvie adenocarcinomas posed by their infiltrative pattern into submucosa. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1688552293761001

Aim: Gemcitabine is the first chemotherapeutic agent to show clinical benefits in pancreatic cancer patients. While interindividual variability in chemoresponse is observed, genetic factors that affect drug metabolism have not been clearly defined. The purpose of this study is to evaluate the relationships between genetic polymorphisms and therapeutic efficacy in pancreatic cancer patients treated with gemcitabine. Patients & methods: The study population consisted of 102 pancreatic cancer patients who had been treated with a gemcitabine-based chemotherapeutic regimen. 102 genetic polymorphisms were selected from 23 genes involved in the metabolism and action sites of gemcitabine and screened for polymorphisms using the MassARRAY® system. The polymorphisms and haplotypes were analyzed in relation to overall survival (OS), time-to-progression (TTP) and disease progression. Results: CMPK1 360C>T was significantly associated with OS, TTP and disease progression (p = 0.042, 0.007 and 0.040, respectively, in a dominant genetic model). Additionally, CMPK1 240G>T was correlated with OS and TTP. The frequencies of the haplotypes for the CMPK1, SLC28A1, DCTD and TLE4 genes differed according to disease progression. Conclusion: Genetic polymorphisms in genes related to metabolism and action sites of gemcitabine showed associations with the therapeutic efficacy, in terms of OS, TTP and disease progression in pancreatic cancer patients treated with gemcitabine-based chemotherapy. In particular, polymorphisms of the CMPK1 gene seem to provide important prognostic information. Original submitted 21 February 2012; Revised submitted 7 May 2012

Background There is no standardization of the use of suction during puncturing of a target in pancreatic EUS-guided FNA (EUS-FNA). It is also debatable whether expressing aspirates from the needle by the traditional method of reinserting the stylet is more effective than by air flushing, which is easier and safer. Objective To optimize sampling techniques in pancreatic EUS-FNA. Design Prospective, comparative trial. Setting Tertiary-care referral center. Patients Eighty-one consecutive patients with solid pancreatic masses. Intervention Four punctures were performed for each mass in random order by a 2 × 2 factorial design. Sample quality and diagnostic yield were compared between samples with suction (S+) versus no suction (S-) and expressed by reinserting the stylet (RS) versus air flushing (AF). Main Outcome Measurements Sample quality by the number of diagnostic samples, cellularity, bloodiness, and air-drying artifact; diagnostic yield by accuracy, sensitivity, and specificity. Results The number of diagnostic samples (72.8% vs 58.6%; P = .001), cellularity (odds ratio [OR] 2.12; 95% confidence interval [CI], 1.37-3.30; P P P = .004), and sensitivity (82.4% vs 72.1%; P = .005) were higher in S+ than in S-. Bloodiness was lower in AF than in RS (OR 1.16; CI, 1.03-1.30; P = .017). Limitations Single-center trial, 2 kinds of needle gauges, and no immediate cytopathology evaluation. Conclusion Puncturing with suction and expressing by air flushing may be used preferentially in pancreatic EUS-FNA because they were more effective and convenient techniques. (Clinical trial registration number: NCT01354795.)

BACKGROUND/AIMS Although primary small intestinal carcinoma (SIC) is morphologically similar to colorectal carcinoma and shares many of the genetic changes of carcinogenesis, little is known about the role of defective mismatch repair (MMR) genes involved in the SIC. The aim of this study is to investigate the role of defective MMR genes and correlation between clinicopathological factors and loss of MMR protein in SIC. METHODOLOGY A total of 195 SIC cases were collected from 20 institutions in Korea and tissue microarrays (TMA) were made. The loss of expression of hMLH1, hMSH2 and hMSH6 was examined by immunohistochemistry (IHC). RESULTS The loss of expression of hMLH1, hMSH2 and hMSH6 was identified in 25/193 (13.0%), 25/193 (13%) and 29/195 (15%), respectively. The loss of hMSH2 expression was associated with retroperitoneal seeding. Patients with loss of hMSH6 expression had a tendency to invade deeply and a higher frequency of pancreas invasion. The loss of hMSH6 expression was associated less frequently with peritumoral adenoma. There was no survival difference by MMR protein expression status. CONCLUSIONS The loss of MMR protein was associated with some distinct clinicopathological features. MMR pathway seems to be major pathway in carcinogenesis of SICs. MMR defect seems to be related with sporadic-microsatellite instability (MSI).

Due to its limited availability there has been very little research on the mesenchyme of the nail unit. Recently, we discovered specialized mesenchymal cells beneath the nail matrix and proposed to call them onychofibroblasts. The purpose of this study was to further delineate more precisely by histology and immunohistochemistry the specialized nail mesenchyme.Thirty supernumerary digits were obtained during operations to correct polydactyly. Longitudinal and transverse sections were obtained from formalin-fixed paraffin-embedded blocks. In sections stained with haematoxylin and eosin, a mesenchymal area that showed much more cellularity and less eosinophilic, loose connective tissue was identified beneath the nail matrix and nail bed. Using Alcian blue staining, mucin was detected in this mesenchymal area below the nail matrix and nail bed. Immnunohistochemically, CD10 and versican were expressed strongly in the mesenchyme containing onychofibroblasts under the nail matrix and nail bed.These results demonstrate the presence and localization of a specialized nail mesenchyme containing onychofibroblasts in a well-defined area beneath the nail matrix and nail bed. Thus, we propose the term onychodermis for this specialized nail mesenchyme that is histologically and immunohistochemically distinct from the dermis of other parts of the nail unit.

Various skin eruptions are encountered during hematopoietic stem cell transplantation (HSCT) of children with hematologic malignancies. Engraftment syndrome (ES) is a disease characterized by fever, weight gain, maculopapular skin rash and noncardiogenic pulmonary edema. ES occurs during neutrophil recovery without identifiable causes of infection. Early detection of ES is critical to reduce mortality and morbidity, but identical morphologic changes found in skin lesions from ES and graft-versus-host disease (GVHD) are a challenging problem for histology-based diagnosis. To resolve this issue, immunopathologic changes in skin lesions of ES were studied. Five skin biopsies from patients with symptoms clinically compatible with ES were retrieved and compared to 15 age- and sex-matched cases of acute GVHD with antibodies to CD3, CD4, CD8 and CD1a. Mean numbers of epidermal CD8+ cells and CD1a+ cells were lower in ES than in GVHD. However, there were no significant differences in mean score of GVHD grade, mean numbers of lymphoid cells, CD3+ cells, or CD4+ cells. In the setting of HSCT in children, the dominance of CD4+ cells and a decreased number of CD1a+ cells in the epidermis are specific features for the skin lesions of ES.

BACKGROUND/AIMS Intraductal papillary mucinous neoplasms (IPMN) are precursor lesions of fatal pancreatic cancer. Physiological function of microRNA is to regulate the stability and translation of mRNA. The aberrant microRNA expression is commonly observed in many cancers. The aim of this study was to analyze the expression pattern of microRNA in IPMN and evaluate the role of the microRNA. METHODS Using two paraffin-embedded IPMN tissues, microRNA expression of normal tissue, IPMN adenoma and carcinoma were compared by cDNA-mediated annealing, selection, extension and ligation microarray assay. Using real time PCR, expression levels of aberrantly up-regulated microRNAs were assessed in another 20 IPMNs, four pancreatic cancer cell lines (Panc1, MiaPaCa-2, XPA-3, BxPC-3) and immortalized pancreatic ductal cell line (HPNE). Effect of suppressing highly over-expressed two microRNAs in pancreatic cancer cell lines with anti-microRNA inhibitors were evaluated using CCK-8 assay. RESULTS Among aberrantly expressed 122 microRNAs in IPMN, miR-552, miR-25*, miR-183, miR-1300, miR-196a, miR-182*, and miR-30c-1* were consistently increased more than 3-fold. On average, miR-196a and miR-183 increased 10,824 folds and 26,519 folds in four pancreatic cancer cell lines compared with HPNE. These two microRNAs were also over-expressed in 20 IPMNs compared with HPNE. After applying anti-miRNA inhibitors, cell survival of four pancreatic cancer cell lines decreased by 24.5% with anti-miR-196a and by 14.2% with anti-miR-183 on average. CONCLUSIONS Aberrant expression of 122 microRNAs was observed in IPMN. Two microRNAs, miR-196a and miR-183-increased in IPMN and pancreatic cancer cell lines compared with immortalized dancreatic ductal cell line. The inhibitions of these microRNAs repressed cell proliferation of pancreatic cancer cell lines. (Korean J Gastroenterol 2011;58:190-200).

We studied to identify the clinicopathological features, treatment outcome, and prognostic factors for patients with gastrointestinal and hepatopancreaticobiliary neuroendocrine tumor (NET).Between February 2001 and May 2006, a total of 470 patients were diagnosed with NET arising from the gastrointestinal tract, pancreas, and hepatobiliary system. The retrospective patient cohort was obtained and analyzed.The male to female ratio was 1.5:1, and the median age was 55 years (range, 16-81). The most common primary site was the rectum (55.8%). Overall 29 (6.2%) originated from the hepatobiliary system. At initial presentation, 60 patients (12.8%) showed distant metastases. Curative surgery or endoscopic resection was performed in 401 patients. Histopathological distributions were as follows: well differentiated tumor (82.1%), well differentiated carcinoma (10.2%) and poorly differentiated carcinoma (7.7%). The frequency of the poorly differentiated type was somewhat higher in the hepatobiliary system than in the pancreas and gastrointestinal tract (44.8, 15.4 and 2.8%, respectively, P0.05). The estimated 5-year overall survival rate for all patients was 89.6%. Multivariate analysis showed that distant metastases (P = 0.018), origin from the hepatobiliary system (P0.001) and poorly differentiated neuroendocrine carcinoma (P0.001) were independent predictors for poor survival outcome.Patients with locoregional NET had a favorable long-term survival after curative resection. Distant metastases, hepatobiliary localization and a poor degree of tumor cell differentiation were poor prognostic factors. Further investigational approaches for treatment of advanced disease are needed.

Abundant recent data suggest that sessile serrated adenoma/polyp (SSA/P) is an early precursor lesion in the serrated pathway of carcinogenesis. It is believed that SSA/Ps develop cancer by an SSA/P-dysplasia-carcinoma sequence. Hyperplastic polyps (HPs) share some histologic and molecular characteristics with SSA/P, but it is unclear whether SSA/Ps are derived from HPs or whether they develop by a different pathogenetic pathway. Previous studies have shown that serrated polyps from Korean patients show different prevalence rates of certain molecular abnormalities compared with similar lesions from American patients, and this suggests that lifestyle and dietary factors may influence the serrated neoplasia pathway. The purpose of this study was to evaluate the molecular features of HPs and SSA/Ps, the latter both with and without dysplasia, from Korean patients and to compare the findings with similar lesions from American patients. One hundred and eleven serrated polyps, consisting of 45 HPs (30 microvesicular, 11 goblet cell, 4 mucin depleted) and 56 SSA/Ps (36 with dysplasia, 20 without dysplasia), were retrieved from the pathology files of a large medical center in Korea and 38 SSA/P from American patients were evaluated for BRAF and KRAS mutations, microsatellite instability, and hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT), hMLH1, adenomatous polyposis coli (APC), p16, methylated in tumor-1 (MINT-1), MINT2, and MINT31. Methylation of hMLH1 was performed using 2 different sets of primers. Twenty-three conventional adenomas from Korean patients were included as controls. The data were compared between polyp subtypes and between polyps in the right versus the left colon. With regard to HP, KRAS mutations were present in 31.1% of polyps and BRAF mutations in 46.7% of polyps. KRAS mutations were significantly more common in goblet cell HP and BRAF in microvesicular HP (MVHP). Methylation of MGMT, hMLH1, APC, p16, MINT1, MINT2, and MINT31 were present in 42.2%, 64.4% (and 24.4%), 37.8%, 60%, 68.9%, 51.1%, and 60% of HPs. CpG island methylator phenotype high was noted in 60% of HPs. Methylation of hMLH1, p16, MINT2, and MINT31 were more frequent in MVHPs compared with other types of HPs. In contrast, SSA/Ps showed KRAS and BRAF mutations in 12.5% and 60.7% of cases, respectively. Methylation of all tumor-related genes, except hMLH1 (23.2% using 1 type of primers) and APC (37.5%), occurred in >50% of lesions, and CpG island methylator phenotype (CIMP) high was noted in 76.8% of cases. None of the molecular findings were significantly more common in SSA/P with, versus those without, dysplasia, but only 2 of the 36 polyps with dysplasia were of the conventional adenomatous type; the remainder (34 of 36) was of the serrated type. Nevertheless, both SSA/P with conventional adenomatous dysplasia showed methylation of MGMT, APC, MINT1, and MINT31 and were CIMP high. BRAF mutations, methylation of most tumor related genes, and CIMP high occurred more frequently in HPs and SSA/Ps in the right colon, compared with the left colon. In fact, no significant differences were observed between HPs and SSPs of the right colon and HPs and SSA/Ps from the left colon. Furthermore, compared with American patients, Korean male individuals were affected more frequently than female individuals, and both BRAF mutations and hMLH1 methylation were less frequent in the latter compared with the former. We conclude that HPs and SSA/Ps in Korean patients share some, but not all, clinical and molecular characteristics to those that occur in Americans. The data support the theory that the right and left colon are biologically different with regard to susceptibility to serrated cancer, and that anatomic location (right vs. left) may be a more significant risk factor of progression than the histologic type of polyp. Our data also support the theory that right-sided MVHPs may be a precursor to SSA/P.

Background The relative frequency and the clinicopathological characteristics of lymphoma may vary according to geography and ethnicity. Data are limited regarding the features of cutaneous lymphoma (CL) presented according to the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC) classification (2005) in Korea. Objective The study determined the relative frequency of CL in Korea and presented the clinical relevance of CL based on the WHO–EORTC classification. Methods We reclassified the cases of CL collected over a 16-year period in a tertiary institution–based dermatologic setting in Korea. Results In all, 164 cases were divided into 96 primary and 68 secondary CL. The group of primary CL consisted of T- and natural killer–cell lymphomas (84.3%), B-cell lymphomas (13.5%), and immature hematopoietic malignancies (2%). The Korean population presented with a higher rate of T-cell and natural killer–/T-cell CL and a lower rate of cutaneous B-cell lymphoma than Western countries. Compared with 2003 Korean data, the rate of mycosis fungoides was lower and the rate of nasal and nasal-type natural killer–/T-cell lymphomas was higher. Limitations This study was retrospective and based on a single-center experience. Conclusion As the relative frequency of lymphomas differs widely with geography and ethnicity, there is a need to collect more data to describe the epidemiologic characteristics in the Far East.

Objective: To compare results of liquid-based cytology (LBC) and the conventional smear method (SMEAR) when performing endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for lesions of suspected pancreatic malignancy without an on-site cytopathologist. Study Design: Fifty-eight patients were prospectively enrolled between July and December 2009. Aspirates obtained from the first needle pass were randomized either to SMEAR or LBC. Another sample from the second needle pass was allocated to the other method. The rest of the aspirates from the third or later needle passes were used for SMEAR. Diagnostic accuracy was compared and related factors were pursued. Results: Although both methods were 100% specific, LBC was inferior to SMEAR in terms of sensitivity, negative predictive value, and accuracy. However, LBC provided correct diagnoses in 2 out of 3 cases of false negatives for malignancy by SMEAR in which blood was highly contaminated. Although no factor was identified for LBC, low blood contamination and more than 3 needle passes were related with accurate diagnosis in SMEAR. Conclusion: LBC was less accurate than SMEAR when performing pancreatic EUS-FNA without an on-site cytopathologist. However, LBC might serve as a good complement to SMEAR if blood contamination is profound.

In patients with hilar cholangiocarcinoma (HC), longitudinal tumor extent is important for curative resection. The purpose of this study was to evaluate the longitudinal extents of HC using transpapillary intraductal ultrasonography (IDUS) for optimal surgical planning.From July 2006 to April 2010, a total of 42 patients with borderline resectable HC were enrolled at Samsung Medical Center, a tertiary referral hospital in Seoul, Korea. All patients were evaluated using multi-detector computed tomography (MDCT), endoscopic retrograde cholangiopancreatography (ERCP) and IDUS. The new modified Bismuth Type (MBT) classification, in which the traditional Bismuth type IV stage is divided into stages IVa and IVb, was used to determine whether the tumor invaded the left lateral section. Among the subtypes of HC, the periductal infiltrative type (PDI) and intraductal papillary neoplasm of the bile duct (IPN-B) were compared. The accuracies of CT, ERCP, and IDUS were assessed through comparison with the postoperative histology findings.A total of 42 patients were prospectively enrolled, and the tumor extent could be assessed histologically in 30 patients. The accuracies of CT, ERCP, and IDUS were 66.6%, 60%, and 90%, respectively. The accuracy of IDUS was 85.7% in 21 patients with PDI and 100% in nine patients with IPN-B.Hilar cholangiocarcinoma staging based on IDUS findings was highly accurate. We therefore highly recommend using IDUS for optimal surgical planning in patients with borderline resectable HC.

PURPOSE To evaluate clinical outcomes and safety of adjuvant chemoradiation therapy (CRT) with capecitabine after resection of pancreatic adenocarcinoma at a single institution. PATIENTS AND METHODS A retrospective analysis of patients undergoing adjuvant CRT with capecitabine after resection of pancreatic ductal adenocarcinoma between 2004 and 2007 yielded a total of 55 patients. Capecitabine was administered at 850 mg/m(2) twice daily every day per week radiotherapy (45 Gy in 25 fractions) over the 5 weeks. Sixteen percent of patients (N=9) went on to receive gemcitabine. RESULTS Of 55 patients, 42 had curative (R0) resection and 13 had incomplete resection (R1). Median overall survival (OS) and progression free survival were 18.3 and 8.0 months for all patients, respectively. Patients receiving additional gemcitabine after adjuvant CRT with capecitabine showed better OS and progression free survival than those not receiving additional gemcitabine (P

Mucosal and acral melanomas have demonstrated different genetic alterations and biological behavior compared with more common cutaneous melanomas. It was recently reported that gain-of-function KIT mutations and/or copy number increases are more common in mucosal and acral melanomas. Thus, we studied the frequency and pattern of KIT aberrations in mucosal and acral melanomas in Korea. We analyzed 97 patients who were pathologically confirmed with mucosal or acral melanoma between 1997 and 2010 at Samsung Medical Center. Of the 97 melanoma patients, 92 were screened for mutations in KIT exons 11, 13, 17, and 18, BRAF and NRAS genes. KIT copy number was assessed by quantitative, real-time PCR. Of the 97 patients, 55 (56.7%) were mucosal, 40 (41.2%) were acral melanoma, and two were of unknown primary origin. Among seven cases with KIT mutation, five (60.0%) occurred in exon 11, one (20.0%) in exon 17, and one (20.0%) in exon 13. Point mutations were the most common, resulting in substitutions in exon 11 (K558R, T574A, L576P, and V559A), exon 13 (N655K), and exon 17 (N822K). A novel Thr574Ala (c.1720AG) KIT mutation, which has not been reported in melanoma or other tumor types, was identified in one genital melanoma case. Of the 97 mucosal or acral melanoma specimens, 49 were tested for KIT gene copy number changes using quantitative PCR. Increased KIT copy number was identified in 15 patients: seven (40%) of 20 acral melanomas and eight (31%) of 26 mucosal melanomas. Our study implicates that a significant proportion of acral and mucosal melanomas have KIT mutations in Asian population.

In the frozen longitudinal section of the nail unit, CD10 was previously found in nail mesenchymal cells beneath nail matrix, and we proposed calling the nail mesenchymal cells onychofibroblasts. In this study, to further characterize nail mesenchyme containing onychofibroblasts, we examined the expression of several mesenchymal markers immunohistochemically in transverse paraffin sections of the nail unit. CD10 was strongly expressed in the nail mesenchyme containing onychofibroblasts beneath the nail matrix. However, CD10 was not observed in dermal fibroblasts and surrounding extracellular matrix of the lateral nail fold (LNF), except around blood vessels and eccrine structures. In addition, versican was expressed diffusely in the nail mesenchyme containing onychofibroblasts in contrast to the dermis of LNF. Fibrillin, which is a major component of elastic fiber in the dermis, was expressed very weakly on the nail mesenchyme below the nail matrix but was expressed strongly in the dermis of LNF. These findings support the existence of specialized nail mesenchyme containing onychofibroblasts that is distinguished from the dermis of LNF.

Background: Lymph node metastasis is one of the most important adverse prognostic factors for pancreatic cancer. The aim of this study was to identify novel lymphatic metastasis-associated markers and therapeutic targets for pancreatic cancer. Methods: DNA microarray study was carried out to identify genes differentially expressed between 17 pancreatic cancer tissues with lymph node metastasis and 17 pancreatic cancer tissues without lymph node metastasis. The microarray results were validated by real-time PCR. Immunohistochemistry and western blotting were used to examine the expression of farnesoid X receptor (FXR). The function of FXR was studied by small interfering RNA and treatment with FXR antagonist guggulsterone and FXR agonist GW4064. Results: Farnesoid X receptor overexpression in pancreatic cancer tissues with lymph node metastasis is associated with poor patient survival. Small interfering RNA-mediated downregulation of FXR and guggulsterone-mediated FXR inhibition resulted in a marked reduction in cell migration and invasion. In addition, downregulation of FXR reduced NF-κB activation and conditioned medium from FXR siRNA-transfected cells showed reduced VEGF levels. Moreover, GW4064-mediated FXR activation increased cell migration and invasion. Conclusions: These findings indicated that FXR overexpression plays an important role in lymphatic metastasis of pancreatic cancer and that downregulation of FXR is an effective approach for inhibition of pancreatic tumour progression.

Aims Pancreatic β-cell function indexes have been suggested using the oral glucose tolerance test (OGTT). Here, we investigated whether β-cell function index from the OGTT reflects pancreatic β-cell area in Korean patients. Methods The study consisted of 45 patients who underwent pancreatectomies. Before operation, a 75-g OGTT was performed. Immunohistochemical staining was performed, and indexes of β-cell function from the OGTT data were compared with the pancreatic β-cell area. Results The β-cell area of the pancreas was 1.07 ± 0.33% in the normal glucose tolerance group, 1.71 ± 0.85% in the pre-diabetes group (impaired glucose tolerance and impaired fasting glucose), and 1.08 ± 0.57% in the diabetes group. The β-cell area of the pre-diabetes group was significantly higher than that of the diabetes group. Pancreatic β-cell area showed a significant correlation with a homeostasis model assessment of β-cell function (r = 0.358, P = 0.016), disposition index (r = 0.336, P = 0.024), fasting glucose (r = −0.359, P = 0.015), and the C-peptide/glucose 30 min ratio (r = 0.319, P = 0.035). Conclusions Some parameters of β-cell function from the OGTT showed a significant relationship with the β-cell area of pancreas.

PURPOSE: This study evaluates the anti-tumor effect of regional chemotherapy compared with chemoembolization in an animal model. MATERIALS AND METHODS: Twenty-one rabbits bearing VX2 liver tumors were divided into the following four groups: (a) the transarterial (TA) group (n=6) received a transarterial injection of doxorubicin through the hepatic artery (1 mg/kg); (b) the transarterial and transportal (TAP) group (n=6) received injections of doxorubicin through both the hepatic artery (1 mg/kg) and the portal vein (1 mg/kg); (c) the transarterial chemoembolization (TACE) group (n=6) received a transarterial injection of doxorubicin (1 mg/kg) followed by gelatin sponge embolization; and (d) the control group (n=3) received no treatment. With the use of computed tomography, tumor growth rates were calculated and microscopic examinations were performed to evaluate the extent of tumor necrosis. RESULTS: Seven days after each treatment, the mean tumor growth rates were 216.7%±189.0% in the TA group, 77.1%±73.9% in the TAP group, and 489.5%±352.1% in the control group; there were no significant differences in tumor growth rates (P = 0.057). The tumor growth rate of the TACE group could not be evaluated due to extensive liver necrosis. The mean tumor necrosis rates were 41.9%±11.5% in the TA group, 51.4%±11.1% in the TAP group, 94.7%±3.5% in the TACE group, and 29.3%±6.7% in the control group; the TACE group showed significantly higher tumor necrosis than any other groups. CONCLUSION: Single session regional chemotherapy has limited anti-tumor effects when compared with TACE in the rabbit VX2 tumor model.

Frequently associated with hormone refractory prostate cancer are neuroendocrine cells. Because these cells do not express androgen receptors and are castration-resistant, further understanding the mechanism of neuroendocrine differentiation (NED) of prostate cancer cells may yield novel intervention methods in hormone refractory prostate cancer. In this regard, the present study investigated the effect of macrophages on prostate cancer NED.THP-1 and LNCaP or RAW264.7 and TRAMP-C2 cell line co-cultures were used to investigate NED-macrophage interactions. Also interleukin-6 (IL-6) knockout mice and macrophage-depleted mice were used to test NED in vivo.We found that co-culturing with THP-1 human monocytic cell line and RAW 264.7 murine macrophage cell line led to the NED of LNCaP and TRAMP-C2 prostate cancer cells, respectively. Specifically, the conditioned media of activated macrophages stimulated the expression of parathyroid hormone-related peptide (PTHrP), a marker of NED, in both LNCaP and TRAMP-C2 cells. Mechanistically, bone morphogenetic protein-6 (BMP-6) derived from prostate cancer cells increased the expression of IL-6 in macrophages. Subsequently, IL-6 induced the NED of prostate cancer cells. When this feedback loop was disrupted with neutralizing antibodies to either BMP-6 or IL-6, NED was no longer observed. In human prostate cancer tissues, neuroendocrine cells frequently co-localized with macrophages and BMP-6. In mice, the removal of IL-6 or macrophages blocked the BMP-6-induced NED of prostate cancer cells.Therefore, we propose that BMP-6 secreted by prostate cancer cells induces IL-6 expression in macrophages; IL-6, in turn, stimulates the NED of prostate cancer cells.

Intraductal tubulopapillary neoplasm (ITPN) has been recently reported in pancreas. We experienced an unusual intraductal growing bile duct tumor, which showed the same histopathologic and immunostaining profiles as ITPN of pancreas. A 72-year-old female patient visited hospital due to intrahepatic stone. The hilar bile duct tumor was detected and incidental lung mass was found in systemic evaluation. The histopathologic finding of the two biopsy lesions was different. The lung tumor was an adenocarcinoma, and the bile duct tumor showed poorly differentiated carcinoma with eosinophilic cytoplasm. Lung lobectomy and hemihepatectomy were performed under the impression of double primary neoplasms of the lung adenocarcinoma and oncocytic variant of the biliary papillary tumor. However the histopathologic findings and immunostaining profiles of the two resected tumors were the same. Both the lung and bile duct tumors showed a tubulopapillary pattern with high-grade nuclear atypia. Pathologic findings were the same as a recently reported ITPN of the pancreas. Eosinophilic cytoplasm of the bile duct tumor was not oncocytic cytoplasm but pyknotic change due to necrosis. Here, we report the first case of ITPN of the bile duct with lung metastasis. The tumor in this case does not fit with any categories in the current biliary tumor classification. We speculate that this may be the first case of biliary ITPN.

Background and Aim: In this study, we analyzed the clinical and pathological features of biliary intraductal papillary neoplasms (IPN-B) according to the location of the tumors. Methods: A total of 55 patients with IPN-B were analyzed. We divided them into three groups: common bile duct (CBD), hilar, and intrahepatic duct (IHD) groups. The clinical and laboratory findings, cell types, depth of invasion, malignancy, existence of stones, lymph node metastasis, recurrence, and survival rate were analyzed. Results: There was no difference in the depth of invasion, lymph node metastasis, and coexistence of stones between the three groups. There were four different cell types; the intestinal cell type was the most common type in each group. The gastric cell type was prevalent in the IHD and hilar groups (58.3% and 33.3%, respectively). Invasive colloid carcinoma mainly showed the intestinal cell type, and tubular carcinoma showed the pancreaticobiliary cell type. There was a trend that malignancy was more prevalent in the CBD group (94.1%) than in the hilar group (64.3%) and IHD group (79.2%), but there was no statistically significant difference. There was no difference in the recurrence rate and the 3-year survival rate between the three groups. Conclusion: IPN-B showed no difference in the malignancy and survival rates according to the location of the tumors. Because IPN-B show good prognosis after surgery, aggressive surgical resection for the treatment of IPN-B is recommended.

Lymph node (LN) metastasis is one of the most important adverse prognostic factors for pancreatic cancer. The aim of this study was to identify novel lymphatic metastasis-associated markers for pancreatic cancer. DNA microarray analysis was used to determine and compare the expression profiles of 17 pancreatic cancer tissues with LN metastasis and 17 pancreatic cancer tissues without LN metastasis. The microarray results were validated by real-time reverse transcription-polymerase chain reaction and immunohistochemistry. Only 58 genes were differentially expressed between the two groups with a difference in signal intensity ratio greater than a 1.5-fold change. Of these genes, 30 were significantly down-regulated in the LN metastasis group. Among five selected down-regulated genes for validation using real-time PCR, the expression of DST, FosB, RGS16, and CXCL12 was significantly lower in the LN metastasis group. Immunohistochemical analysis confirmed RGS16 and FosB underexpression in pancreatic cancer tissues with LN metastasis. RGS16 and FosB underexpression was associated with poor patient survival. Our findings show that RGS16 and FosB are underexpressed in pancreatic cancer with lymph node metastasis and associated with reduced survival, suggesting that RGS16 and FosB might be prognostic markers for pancreatic cancer.

Adenosquamous/squamous cell carcinoma (AS/SCC) of the gallbladder is rarely encountered and accounts for 1.4-10.6% of all gallbladder carcinomas (GBCs). This study was conducted to investigate the clinicopathologic features of AS/SCC of gallbladder.The authors retrospectively reviewed 16 cases of pathologically proven AS/SCC of the gallbladder among 404 patients who underwent surgery for GBC from October 1994 to March 2009. Forty-eight conventional GBC patients were selected as controls after matching for age and gender.Mean patient age was 60.2 years and half were male. Tumor stages in the case group were significantly more advanced than the control group (P0.001). R0 resection rates in cases and controls were 50% and 81.2% (P = 0.022). Overall 1-year survival in the case group was significantly poorer than in the control group (18.8% vs. 87.3%, P0.001). However, no significant difference in disease-free survival rates was found between cases and controls after R0 resection (P = 0.072).AS/SCC of the gallbladder is often diagnosed at an advanced stage, which results in non-curative surgical resection and a poorer prognosis than conventional GBC. However, curative surgical resection of AS/SCC of the gallbladder might result in disease-free survival rates that are comparable with those of conventional GBC.

The authors present a case of histologically proven bronchus-associated lymphoid tissue (BALT) lymphoma of the lung in a patient with primary Sjogren's syndrome that manifested on thin-section CT scan as a mosaic pattern of inhomogeneous attenuation due to mixed small airway and infiltrative abnormalities

Primary hepatic carcinosarcoma which has comprised of a mixture of both carcinomatous and sarcomatous elements is very rare. This tumor has been variously called as carcinosarcoma, pleomorphic large cell carcinoma, giant cell carcinoma, or undifferentiated carcinoma. Only less than 20 cases of carcinosarcoma of the liver have been reported sporadically up to now worldwide. Herein, we present a case of carcinosarcoma of the liver along with a review of the literatures.

This study evaluated the significance of cystic fluid analysis and radiologic findings in the differential diagnosis of biliary cystadenomas (BCA) and hepatic simple cysts (HSCs).BCA are premalignant lesions. The treatment of choice is surgical excision. It is important to differentiate BCA from HSCs because they have different clinical significances and treatment plans. However, it is difficult to preoperatively differentiate a BCA from a HSC.This retrospective study was done with 31 patients suffering from pathologically diagnosed BCA or HSC. All patients underwent surgery between May 1995 and June 2008 at a single institution and had cystic fluid analysis preoperatively or intraoperatively.We discovered no statistically significant differences in cystic fluid carbohydrate antigen 19-9 (CA 19-9) levels or carcinoembryonic antigen levels when comparing BCA (n=17) and HSCs (n=14). BCA were significantly more frequently associated with female sex (17/17 vs. 10/14, P=0.032), presence of a septum (16/17 vs.5/14, P=0.001), and septal thickening (8/17 vs. 1/14, P=0.021). All 3 cases with calcifications belonged to the BCA group, but sample size was too small to demonstrate statistical significance. There were no statistically significant differences in other clinical and radiologic findings including age, presence of symptoms, serum tumor markers, serum chemistry, size, location, lobulation, septal enhancement, wall enhancement, wall thickening, mural nodule, or biliary dilatation.Cystic fluid carbohydrate antigen 19-9 levels and carcinoembryonic antigen levels were not useful for differential diagnosis of BCA vs. HSC. BCA were more common than HSCs in females, patients with a septum, and patients with septal thickening.

The clinical manifestations of autoimmune pancreatitis (AIP) are diffuse pancreatic swelling, diffuse irregular narrowing of the main pancreatic duct, and increased serum IgG or positive serum autoantibody. Clinically, AIP can be improved dramatically with oral steroid therapy. In this report, we describe a 62-year-old woman diagnosed as autoimmune pancreatitis six years after onset of jaundice, who presented with uncontrolled blood glucose levels. The laboratory tests revealed obstructive jaundice, and the computed tomography of the pancreas showed pancreatic swelling. After six years of onset, she was diagnosed with AIP and successfully treated with steroid treatment.

Mucin-producing bile duct tumors are characterized by intraductal papillary tumors producing large amounts of mucin. The tumor comprises macroscopically prominent intraductal papillary neoplastic epithelia and produces a large amount of viscid mucin, resulting in dilatation of the bile ducts. The surface of the tumor is frond-like, velvety, or serrated. The tumor exhibits five intraductal growth patterns; polypoid intraductal growth, mucosal spreading growth, cast-like intraductal growth, cystic tumor, and intraductal floating tumors. Imaging features reflect the interplay between the morphology of the tumor, the amount of mucin production, and biliary dilatation. This review article describes the radiological manifestations of the tumor, based on pathological-radiological correlation and biological behavior.

Papillary tumours of the bile ducts are characterized by an intraluminal papillary mass in association with bile duct obstruction and dilatation. Some of these tumours secrete an excessive amount of mucin, which may disturb bile flow and cause severe ductal dilatation. The condition currently is most commonly described as intraductal papillary mucinous tumour or neoplasm (IPMN) of the bile ducts. In 1996, Adsay et al. proposed the term, intraductal oncocytic papillary neoplasm (IOPN) for a distinctive cystic intraductal tumour with oncocytic features and mucin production as a subtype of IPMN of the pancreas. However, oncocytic (i.e., eosinophilic) changes are extremely rare in the biliary system. To our knowledge, fewer than 10 cases of IOPN of the liver have been reported previously. As the diagnostic concept of IOPN of the biliary system is a relatively recent introduction and the frequency of this diagnosis is increasing, radiologists need to be familiar with this entity. In this report, two cases of IOPN of the bile duct, comprising a unilocular cystic mass with mural nodules, are presented. The radiological features on ultrasonography (US) and computed tomography (CT) are illustrated and correlated with the pathological findings.

Intraductal papillary neoplasm of bile duct (IPNB) is one of the precursor lesions of cholangiocarcinoma. Although hepatolithiasis has been extensively studied in its association with IPNBs, there had been no comprehensive study of IPNBs with Clonorchis sinensis infection. Twelve IPNBs were selected from 20 surgically resected cholangiocarcinomas, positive for C. sinensis tests (60%) and compared with eight IPNBs, selected from 51 resected cholangiocarcinomas, negative for C. sinensis tests (16%), by histologic and immunohistochemical studies of mucin core proteins and cytokeratin panels. The predominant immuno-phenotype of IPNB cases with Clonorchiasis was pancreatobiliary type (MUC1+/MUC2-/CDX2-; 9/12 cases), while that of IPNB cases with negative for C. sinensis was intestinal type (MUC1-/MUC2+/CDX2+; 6/8; p = 0.04). The prevalence of IPNBs was higher when patients with cholangiocarcinoma had Clonorchiasis. IPNBs with Clonorchiasis tended to have a more pancreatobiliary phenotype, which suggests IPNBs with Clonorchiasis may have a different tumorigenesis pathway from IPNBs with other etiologies.

Many radiologists are unfamiliar with the recently developed World Health Organization classification scheme for neuroendocrine tumors. According to this classification scheme, neuroendocrine tumors are divided into well-differentiated endocrine tumors (carcinoids), well-differentiated endocrine carcinomas (malignant carcinoids), and poorly differentiated endocrine carcinomas on the basis of their location, histologic features, and biologic behavior. Most neuroendocrine tumors have nonspecific imaging characteristics. However, they sometimes have peculiar clinical manifestations and radiologic features, on the basis of which radiologists may infer the specific diagnosis. Neuroendocrine tumors of the gastrointestinal tract originate from the cells derived from the embryonic neural crest, neuroectoderm, and endoderm. They usually produce bioactive substances and show immunoreactivity to neuroendocrine markers. Although neuroendocrine tumors are uncommon, they should be considered in developing the differential diagnosis for gastrointestinal tumors in patients with a typical syndrome or when the tumors have characteristic imaging features.

Aberrant expression of Sonic hedgehog (Shh) has been reported in many human cancers including ductal carcinoma of the pancreas. The intraductal papillary mucinous tumor (IPMT) has been considered as one of the precursor lesions of invasive ductal carcinoma of the pancreas. Shh expression in pancreatic IPMT has not been reported. We investigated an immunohistochemical (IHC) expression of Shh in 55 cases of pancreatic IPMT. We analyzed the IHC expression of Shh in the following histologic grades of tumor: adenoma (AD), moderate dysplasia (MD), noninvasive carcinoma (NIC), and invasive carcinoma (IC), and with the following histologic subtype classification: intestinal, pancreatobiliary, null, and unclassifiable type. IHC Shh expression was noted in 6 (46.2%) of 13 AD, 5 (35.7%) of 14 MD, 12 (80%) of 15 NIC, and 11 (84.6%) of 13 IC. Shh expression was significantly increased in malignant IPMT (NIC+IC) compared with nonmalignant IPMT (AD+MD) (82.1% vs. 40.7%, P=0.0005). IHC Shh expression was found in 11 (68.8%) of 16 intestinal types, 13 (92.8%) of 14 pancreatobiliary types, 8 (38.1%) of 21 null types, and 2 (50%) of 4 unclassifiable types. Intestinal and pancreatobiliary subtypes showed a high expression of Shh compared with the null and unclassifiable type of IPMT. All 3 cases of node metastasis showed IHC Shh expression in tumor cells of metastatic lymph nodes. Therefore, Shh expression may have a critical role in the late stage of carcinogenesis of IPMT, and may impact metastatic progression to the lymph nodes in malignant IPMT.

We report here on the imaging findings of a case of autoimmune cholangitis that involved a segmental bile duct of the liver. Abdominal computed tomogram showed ill-defined low-attenuation lesion at the hilar portion of the right hepatic lobe, and this was associated with peripheral intrahepatic bile duct dilatation. Gadolinium enhanced liver magnetic resonance imaging (MRI) showed wall thickening with periductal enhancement along the segmental tributaries of the right intrahepatic bile duct. The pathologic findings revealed lymphoplasmacytic infiltration and severe fibrosis, indicating autoimmune cholangitis.

To identify differential findings of biliary cystic intraductal papillary mucinous tumor (IPMT) and biliary cystadenoma/cystadenocarcinoma on CT images.Records of 7 patients with biliary cystic IPMT and 17 patients with biliary cystadenoma/cystadenocarcinoma were accessed. A pathologist reviewed gross morphologic and microscopic findings and confirmed the diagnosis. Two radiologists who were blind to the pathologic diagnosis reviewed CT images regarding size of cystic mass, mural nodule, septa, calcification, dilatation of the proximal, and distal bile ducts to the tumor, and the results were analyzed using multivariate analysis.Mural nodule and dilatation of the bile ducts distal to the cystic tumor were more commonly seen in patients with cystic IPMT than in patients with biliary cystadenoma/cystadenocarcinoma and these are statistically significant, the P values being 0.029 and 0.016, respectively. Size of the cystic tumor, presence of septa, calcification, and dilatation of the bile duct proximal to the cystic tumor were not statistically different.Biliary cystic IPMT could be differentiated from biliary cystadenoma/cystadenocarcinoma on CT images based on the presence of mural nodules and dilatation of the bile ducts distal to the cystic tumor.

BACKGROUND. Erlotinib, in combination with gemcitabine, has shown clinical benefits in pancreatic adenocarcinoma patients. The presence of EGFR mutations and increased EGFR copy numbers in pancreatic adenocarcinoma was explored. METHODS. Sixty-six pancreatic cancer patients were included in the analysis. The EGFR mutation was analyzed by DNA sequencing of exons 18–21 in the tyrosine kinase domain. KRAS mutation was analyzed by sequencing codons 12, 13, and 61. Quantitative real-time polymerase chain reaction was performed to analyze the copy number of EGFR. RESULTS. In the current study the EGFR mutation was harbored in only 1 (1.5%) of the 66 inoperable or metastatic pancreatic adenocarcinoma patients. Amino acid substitution was detected in exon 20 of the EGFR gene. Increased EGFR copy numbers (≥3.0 per cell) were detected in 26 (41%) patients. There was only 1 patient, who had a highly increased EGFR copy number (≥6.0 per cell), who died, 2.1 months from the date of diagnosis. The EGFR amplification did not significantly influence survival in pancreatic adenocarcinoma patients (P = .935). Thirty-two (49%) of the 65 pancreatic adenocarcinomas examined harbored a point mutation in codons 12 (n = 31) and 61 (n = 1) of the KRAS gene. The presence of a point mutation in codon 12 adversely influenced survival of pancreatic cancer patients (P = .030). CONCLUSIONS. The incidence of somatic mutations in the tyrosine kinase domains of EGFR was very low and the increased gene copy number of EGFR did not significantly influence survival. Cancer 2007. © 2007 American Cancer Society.

According to the current AJCC staging system, the T stage of distal extrahepatic bile duct carcinoma (EBD) is classified according to the extent of the tumor within or beyond the bile duct wall. However many invasive carcinoma accompany stromal desmoplasia that obscure lower boundary of bile duct wall; it is frequently difficult to clearly define the extent of tumors using the current T classification system. In this study, we validated an alternative T classification system by depth of invasion (DoI; T1

Objectives: It is known that intraductal papillary mucinous neoplasm (IPMN) is associated with a high incidence of extrapancreatic neoplasms. We tried to uncover the characteristics and gene expressions of IPMNs that coexist with other extrapancreatic gastrointestinal cancers. Methods: We retrieved the surgical specimens from 54 IPMN patients, including 7 cases of IPMNs that coexisted with extrapancreatic gastrointestinal cancers. The immunohistochemical staining (p21, Bcl-2, p53, intestinal-type secretory mucin [MUC2], and MUC5AC) and the pathological subtypes of the tumor papillae (the intestinal type, pancreaticobiliary type, null type, or unclassified type) were analyzed. Results: MUC2 expression was noticed more frequently in the IPMN coexisting with extrapancreatic cancers (6/7) than in the IPMN without extrapancreatic cancers (18/47; P = 0.04). There were no differences in p21 (P = 0.12), p53 (P = 0.25), and MUC5AC (P = 1.0) expressions between the 2 groups. IPMN with extrapancreatic cancers was noticed in all subtypes of papillae. Conclusions: Regardless of the subtypes of papillae, transcription of the MUC2 might be related with the synchronous extrapancreatic gastrointestinal cancer development that is seen with IPMN. Therefore, careful systemic surveillance is needed to detect coexisting gastrointestinal cancer for all the subtypes of IPMN with MUC2 expression.

To retrospectively evaluate the imaging features of early bile duct carcinoma and to compare these features with histopathologic findings.The institutional review board did not require its approval or informed patient consent for this study. Twenty-one patients (13 men, eight women; mean age, 60 years; range, 48-75 years) with early bile duct carcinoma that was surgically resected and histopathologically confirmed were included. Ultrasonography (US) was performed in 15 patients, computed tomography (CT) in 21, cholangiography in 18, and magnetic resonance (MR) cholangiography in six. Two radiologists retrospectively reviewed imaging features by consensus; they compared growth pattern of tumors, integrity of the bile duct wall that harbored the tumor, and periductal infiltration with histopathologic findings.Pathologic specimens showed intraluminal tumor growth in all cases. Tumors were confined to the mucosa in 11 patients and involved the fibromuscular layer in 10 patients. In four of the 10 intrahepatic cholangiocarcinomas, four of the five hilar cholangiocarcinomas, and six of the six extrahepatic cholangiocarcinomas, there were intraductal tumor masses and the wall of the tumor-bearing bile ducts was preserved without periductal infiltration on US and CT images. On cholangiograms and MR cholangiograms, tumors were better delineated but the wall invasion could not be evaluated. No difference in image findings was found between carcinoma confined to the mucosa and carcinoma involving the fibromuscular layer.Imaging features of early bile duct carcinoma are a tumor mass in the bile duct lumen and integrity of the tumor-bearing bile duct wall without infiltration outside the wall.

Hedgehog protein is an essential molecule for gastrointestinal tract development, and disruption of hedgehog signaling pathway is linked to some gastrointestinal tumorigenesis. Here, we performed hedgehog immunostaining in periampullary cancer to evaluate the differences according to the location type of cancer and the differentiation of adenocarcinoma.We retrieved surgical specimens from 43 periampullary cancer patients (15 ampulla of Vater cancer, 12 distal common bile duct cancer, 13 pancreatic head cancer, and 3 combined ampulla of Vater/bile duct cancer). Immunohistochemical stain was performed in both normal and cancerous tissue portions of each case using Sonic hedgehog (H-160) rabbit polyclonal antibody. Immunohistochemical stain results were grouped into three groups according to the percentage of positive cytoplasmic stain in tumor volume (unstained:5%, weakly stained: 5-50%, and strongly stained:50%).All of the normal tissue revealed negative immunohistochemical stain while cancerous tissue revealed positivity in 95.3% (41/43 cases). Strongly stained cases were more frequently seen in ampulla of Vater cancers (13/15) and in combined ampulla of Vater/bile duct cancers (3/3) than in distal common bile duct cancers (4/12) and in pancreatic head cancers (3/13) (p=0.002). In addition, strongly stained cases were more frequently seen in well-differentiated adenocarcinoma than the others (p0.001).Most of the periampullary cancers show hedgehog protein expression. In addition, hedgehog protein immunostainings shows stronger expression in ampulla of Vater cancers and in well-differentiated adenocarcinoma.