Role of frozen section assessment for intraductal papillary and mucinous tumor of the pancreas

Intraductal papillary mucinous neoplasms(IPMN) of the pancreas include a spectrum of dysplasia ranging from minimal mucinous hyperplasia to invasive carcinoma and are extensive tumors that often spread along the ductal tree.Several studies have demonstrated that preoperative imaging is not accurate enough to adapt the extent of pancreatectomy and have suggested routinely using frozen sectioning(FS) to evaluate the completeness of resection and also to check if ductal dilatation is active or passive,in order to avoid an excessive pancreatic resection.Separate main duct and branch duct analysis is needed due to the difference in the natural history of the disease.FS accuracy averages 95%.Eroded epithelium on the main duct,severe ductal inflammation mimicking dysplasia and reactive epithelial changes secondary to obstruction can lead to inappropriate FS results.FS results change the planned extent of resection in up to 30% of cases.The optimal cut-off leading to extend pancreatectomy is not consensual and our standard option is to extend pancreatec-tomy if FS reveals:(1) at least IPMN adenoma on the main duct;or(2) at least borderline IPMN on branch ducts;or(3) invasive carcinoma.However,the decision to extend resection must be taken after a multidisciplinary discussion since it does not exclusively depend on the FS result but also on age,general condition and expected prognosis after resection.The main limitation of using FS is the existence of discontinuous("skip") lesions which account for approximately 10% of IPMN in surgical series and can lead to reoperation in up to 8% of cases.

Relationship between the severity of hepatitis C virus-related liver disease and the presence of Helicobacter species in the liver: A prospective study

AIM: To determine the presence of Helicobacter species DNA in the liver of chronic hepatitis C (CHC) patients with and without cirrhosis as compared to controls, and to identify the bacterial species involved. METHODS: Seventy-nine consecutive patients (HBV and HIV negative) with a liver sample obtained after liver biopsy or hepatic resection were studied: 41 with CHC without cirrhosis, 12 with CHC and cirrhosis, and 26 controls (HCV negative). Polymerase chain reactions (PCRs) targeting Helicobacter 16S rDNA and species- specific were performed on DNA extracted from the liver. A gastric infection with H pylori was determined by serology and confirmed by 13C-urea breath test. RESULTS: Overall, Helicobacter 16S rDNA was found in 16 patients (20.2%). Although positive cases tended to be higher in CHC patients with cirrhosis (41.6%) than in those without cirrhosis (17.0%) or in controls (15.4%), the difference was not statistically significant (P =0.08). H pylori-like DNA was identified in 12 cases and H. pullorum DNA in 2, while 2 cases remained unidenti- fied. Gastric infection with H pylori was found in only 2 of these patients. CONCLUSION: Our results do not confirm the associ- ation of Helicobacter species DNA in the liver of CHC patients with advanced liver disease. The lack of correlation between positive H pylori serology and the presence of H pylori-like DNA in the liver may indicate the presence of a variant of this species.

Transient and etiology-related transcription regulation in cirrhosis prior to hepatocellular carcinoma occurrence

AIM:To search for transcription dysregulation that could(1) differentiate hepatocellular carcinoma(HCC)-free from HCC-related cirrhosis(2) differentiate HCC-free cirrhosis related to HCV from that related to alcohol intake.METHODS:Using microarray analysis,we compared transcript levels in HCC-free cirrhosis(alcoholism:7;hepatitis C:7),HCC-associated cirrhosis(alcoholism:10;hepatitis C:10) and eight control livers.The identified transcripts were validated by qRT-PCR in an independent cohort of 45 samples(20 HCC-free cirrhosis;15 HCC-associated cirrhosis and 10 control livers).We also confirmed our results by immunohistochemistry.transcripts which differentiated between alcoholic-related cirrhosis,HCV-related cirrhosis and control livers.They mainly corresponded to down-regulation.Dysregulation of Signal Transduction and Activator of Transcription-3(STAT-3) was found along with related changes in STAT-3 targets which occurred in an etiology-dependent fashion in HCC-free cirrhosis.In contrast,in HCC,such transcription dysregulations were not observed.CONCLUSION:We report that transcriptional dysregulations exist in HCC-free cirrhosis,are transiently observed prior to detectable HCC onset and may be appear like markers from cirrhosis to HCC transition.

TP53基因突变参与成人肝脏未分化(胚胎)肉瘤的生成,不同于Wnt和端粒酶途径:3例病例的免疫组化研究及2例病例的基因相关研究

Background/Aims: Hepatic undifferentiated (embryonal) sarcoma (HUS) is an exc eptional hepatic malignant tumor in adults. Genetic studies were never reported in adult cases. Methods: In this study concerning three cases of HUS occurring i n adult, we studied the three classical ways of carcinogenesis i.e. the TP53 (p5 3), Wnt (CTNNB1/β - catenin and AXIN1) and telomerase (hTERT) pathways. We stu died the expression of p53, β - catenin and telomerase catalytic subunit hTERT by immunohistochemistry in the three cases; we determined TP53 gene mutation in two cases and the genome- wide allelotype, AXIN1, and CTNNB1/β - catenin gen e mutation in one case. Results: Immunohistochemistry showed an overexpression o f p53 in more than 80% of tumoral cells; furthermore, mutations of TP53 were o bserved in two cases, involving the sequence- specific DNA binding domain. In c ontrast, no mutation was found in CTNNB1/β - catenin and AXIN1 genes. Tumoral cells did not show hTERT staining nor nuclear expression of β - catenin. In ad dition, allelotype analysis in one case showed loss of heterozygosity of chromos ome 7p, 11p, 17p, 22q, and allelic imbalance of 1p, 8p, 20q. Conclusions: In thi s report of HUS in three adult patients, we emphasize the role of TP53 pathway i n carcinogenesis of this rare tumor. This point could be of interest for therape utic strategies.

SIMPLE METHOD OF PUNCHING AND RE-LOCATING TISSUES FOR MANUAL CONSTRUCTION OF TISSUE MICROARRAY

A series of human tissue samples and cultured cell lines were formalin-fixed and paraffin-embedded. Specimen cylinder (1.2-1.8mm) were punched by a modified bone marrow biopsy needle and arrayed on a recipient paraffin block. Microscopic analysis on the sections from this tissue microarray (TMA) block demonstrated that the spots of tissues and cells were well preserved, and the cultured cell samples were successfully embedded from 5×10 4 to 2×10 5 in number. These TMA sections were also suitable for immunohistochemistry and RNA in situ hybridization.

DiGeorge综合征:52例病例回顾

The deletion of chromosome 22q11.2 is involved in the majority of DiGeorge or velo-cardiofacial syndrome.The phenotypic variability was noted in the “CATCH 22”acronym.This acronym doesn’t recapitulate the full spectrum of the symptoms.The diagnosis of this syndrome can be done with the prenatal diagnosis, with fetal pathology or with a child alive.Methods.-Review of 52 cases with the microdeletion 22q11.2 Six cases were diagnosed during the prenatal period, 12 cases at fetal pathology examination, and 34 cases during infancy.Results.-Cardiac malformations were the major indications (75%) to search for the microdeletion.The facial dysmorphy was difficult to diagnose during the antenatal period or in dead foetus, thereby it was not often recognized.The renal anomalies usually present in 35%of cases, were diagnosed in only 6 to 16%of the cases in our study.Conclusion.-Phenotypic diversity of the DiGeorge syndrome is important.Its knowledge allows to better determine the indications of the research of the microdeletion.22q11.2.

总胆管孤立性肿瘤:1例转移性黑素瘤病例报道

Primary malignant melanoma of the bile duct is very rare. We report a case of a malignant melanoma involving the common bile duct in a 41-year-old man. The patient presented to the hospital with an isolated jaundice and underwent pancreaticoduodenectomy. Absolute exclusion of a metastatic tumor is not entirely possible.

胎儿至成年期女性肝脏中的男性细胞微嵌合现象

Male microchimerismis frequent in the adult female liver and is attributed to fetal cells originating frompreviousmale offspring. It has never been studied in pregnant women, female children, or fetuses. We examined its frequency and cellular nature in normal and diseased female livers from fetal life to adulthood. Forty-six liver samples from 29 women, 6 female children, and 11 female fetuses were screened for the Y chromosome via polymerase chain reaction (PCR) assay and fluorescent in situ hybridization (FISH). The X chromosome was used as an internal control. A third PCR assay was used for Y genotyping. The Y chromosome was detected in 5 of 6 children, 7 of 11 fetuses, 3 of 9 women with normal liver, 7 of 10 women with chronic hepatitis C, 5 of 6 women with acute liver disease during pregnancy with male offspring, and 2 of 4 nonpregnant women with fulminant hepatitis. In positive samples, the mean XY/XX ratio was 0.012 (±0.004). In women, male microchimerism was correlated with previous male offspring. Male hepatocytes, detected via FISH combined with anti-hepatocyte immunohistochemistry,were observed only in fetuses (4/9) and in postpartem women (4/6). Y genotypes were different from each other in 4 of 5 female livers. In conclusion, male liver microchimerism is frequent in normal and diseased female livers. The presence of male cells in the liver of female children and fetuses is probably due to the transplacental transmission of fetal cells preexisting in the mother and acquired either from previous pregnancy with male offspring or during the mother’s own fetal life.

12例原发性皮肤边缘区淋巴瘤的细胞遗传学和分子分析

Primary low-grade B-cell lymphomas of the skin are separated into marginal zone and follicle center lymphomas according to the recent World Health Organization-European Organization for Research and Treatment of Cancer classification, with distinct histologic and immunohistochemical profiles. Some cases remain difficult to distinguish. The degree of relationship with their extracutaneouscounterparts is currently being investigated on clinical, histologic and molecular grounds.Cytogenetic analysis using fluorescence in situ hybridization was performed on 12 frozen samples of infiltrated skin that had been classified as marginal zone lymphoma (MZL). Chromosomal changes known to be recurrently observed in systemic MZL of the mucosa-associated lymphoid tissue type, and in follicular center lymphoma were analyzed. These included trisomy for chromosomes 3, 7, 12, and 18 as well as t(14;18) IGH/BCL2, t(14;18) IGH/MLT1, and t(11;18) API2/MLT1 translocations. Complementary molecular search of IGH/BCL2 rearrangement using a polymerase chain reaction technique and of API2/MLT1 mRNA expression by reverse transcriptase-polymerase chain reaction were performed. Two cases showed evidence of trisomy 3 at levels varying from 14%to 20%of the analyzed cells. No other chromosomal abnormalities were found with those techniques in the remaining cases. These results demonstrate that known recurrent chromosomal abnormalities rarely occur in primary cutaneous MZLs and suggest the possibility of a variety of initial oncogenic events leading to a common downstream pathway. These data also underline that fluorescence in situ analysis on routine skin punch biopsies represents a reliable tool for the detection of chromosomal changes, but requires consistent dermal infiltration.

从胰腺上皮内瘤至癌的形成:分析在其进展中K-ras的变化

Pancreatic ductal carcinomas are thought to arise from precursor ductal lesions called pancreatic intra-epithelial neoplasias or PanINs. We report the case of a woman suffering from idiopathic chronic pancreatitis associated with PanINs lesions who developed six years later an invasive ductal carcinoma. Immunohistochemistry for p53, HER-2/neu and genetic analysis of K-ras oncogene were performed at different stages of disease and revealed that the PanINs and the carcinoma did not express p53 and HER-2/neu gene products whereas a K-ras mutation was present at the carcinoma stage. The relationship between cancer and chronic pancreatitis and the main difficulties concerning the early diagnostic of pancreatic cancer are discussed.