Hepatic Nodes Research Articles

Solitary focus in the liver in a thyroid cancer patient after a whole body scan with 131 iodine

A 51-year-old woman diagnosed with follicular variant of papillary thyroid carcinoma underwent a total thyroidectomy followed four weeks later by an ablative dose of 3.7 GBq of 131I. A whole body scan 5 days after ablation showed an intense uptake within the thyroid bed and a focal uptake located in the right lung base or liver dome. Computed tomography examination revealed a hypodense hepatic node in segment VII resembling a liver metastasis. Histological examination after ultrasound-guided fine-needle aspiration characterized the lesion as a liver abscess. The abscess regressed after antibiotic therapy. Liver metastases from papillary thyroid carcinoma are uncommon. On the other hand, false positive findings of 131I whole body scans have been described. A focal hepatic uptake might represent a metastasis (rare in papillary carcinomas) or be related to other causes (cysts, inflammation or infection, non-thyroidal neoplasms, etc.).

Intrahepatic Lymphatic Invasion Independently Predicts Poor Survival and recurrences after Hepatectomy in Patients with Colorectal Carcinoma Liver Metastases

Intrahepatic Lymphatic Invasion Independently Predicts Poor Survival and recurrences after Hepatectomy in Patients with Colorectal Carcinoma Liver Metastases

Intrahepatic Lymphatic Invasion Independently Predicts Poor Survival and Recurrences after Hepatectomy in Patients with Colorectal Carcinoma Liver Metastases

D2-40 monoclonal antibody immunoreactivity is specific for lymphatic endothelium and therefore provides a marker of lymphatic invasion. We hypothesized that intrahepatic lymphatic invasion reflects the nodal status of colorectal carcinoma liver metastases and may function as an adverse prognostic factor. A retrospective analysis of 105 consecutive patients who underwent resection for colorectal carcinoma liver metastases was conducted. Intrahepatic lymphatic invasion was declared when either single tumor cells or cell clusters were clearly visible within vessels that showed immunoreactivity for D2-40 monoclonal antibody. The median follow-up time was 124 months. Of 105 patients, 13 were classified as having intrahepatic lymphatic invasion. All tumor foci of intrahepatic lymphatic invasion were detected within the portal tracts. Intrahepatic lymphatic invasion was significantly associated with hepatic lymph node involvement (P = 0.039). Survival after resection was significantly worse in patients with intrahepatic lymphatic invasion (median survival time of 13 months; cumulative five-year survival rate of 0%) than in patients without (median survival time of 40 months; cumulative five-year survival rate of 41%; P < 0.0001). Patients with intrahepatic lymphatic invasion also showed decreased disease-free survival rates (P < 0.0001). Intrahepatic lymphatic invasion thus independently affected both survival (relative risk, 7.666; 95% confidence interval, 3.732-15.748; P < 0.001) and disease-free survival (relative risk, 4.112; 95% confidence interval, 2.185-7.738; P < 0.001). Intrahepatic lymphatic invasion is associated with hepatic lymph node involvement and is an adverse prognostic factor in patients with colorectal carcinoma liver metastases.

Management of the Hepatic Lymph Nodes during Resection of Liver Metastases from Colorectal Cancer: A Systematic Review

Background. Hepatic lymph node involvement is generally considered a contraindication for liver resection performed for colorectal liver metastases. However, some advocate hepatic lymphadenectomy in the presence of macroscopic involvement and others routine lymphadenectomy. The aim of this review is to assess the role of lymphadenectomy in resection of liver metastases from colorectal cancer. Methods. Medline, Embase and Central databases were searched using a formal search strategy. Trials with survival data with a minimum follow-up of 1 year were considered for inclusion. Meta-analysis was performed using Revman. Results. A total of 4230 references were identified. Ten reports of nine studies including 926 patients qualified for the review. The prevalence of nodal metastases after routine lymphadenectomy was 16.3%. The overall 3-year and 5-year survival rates in node-positive patients were 9/151 (11.3%) and 2/137 (1.5%), respectively, compared to 3-year and 5-year survival rates of 424/787 (53.9%) and 246/767 (32.1%) in node-negative patients. The odds ratios for 3-year and 5-year survivals in node positive disease compared to node-negative disease were 0.12 (95% CI 0.06 to 0.24) and 0.08 (95% CI 0.03 to 0.22). There was no randomized controlled trial which assessed the survival benefit of routine or “selective” lymphadenectomy. Conclusion. Currently, there is no evidence of survival benefit for routine or selective lymphadenectomy. Survival rates are low in patients with positive lymph nodes draining the liver irrespective of whether they are detected by routine lymphadenectomy or by macroscopic involvement. Further trials in this patient group are required.

Hepatite infecciosa canina: 62 casos

Os protocolos de necropsias realizadas em 5.361 cães durante um período de 43 anos (1964-2006) foram revisados em busca de casos de hepatite infecciosa canina (HIC) e sessenta e dois (1,2%) casos foram encontrados. A maioria dos 62 cães afetados tinha dois anos de idade ou menos (91,9%). Os sinais clínicos foram anotados nos protocolos de necropsia de 45 cães afetados por HIC e incluíam anorexia (55,6%), apatia (35,6%), diarréia (35,6%), freqüentemente com sangue (43,8% dos casos de diarréia), distúrbios neurológicos (33,3%), vômito (26,7%), petéquias e equimoses nas membranas mucosas e/ou pele (24,4%), hipotermia (20,0%), dor abdominal (15,6%), icterícia (13,3%), aumento de volume e congestão das tonsilas (11,1%), febre (11,1%) e ascite (6,7%). A duração do curso clínico variou de poucas horas a 15 dias. Os principais achados de necropsia incluíram alterações hepáticas (87,1%), linfonodos edematosos, congestos e hemorrágicos (51,6%), líquido sanguinolento, líquido claro ou sangue na cavidade abdominal (35,5%), víbices, sufusões e petéquias sobre a pleura visceral (27,4%) e superfície serosa das vísceras gastrintestinais (24,2%). Em 12,9% dos casos a serosa do intestino tinha aspecto granular. Hemorragias cerebrais nas leptomeninges e na substância do encéfalo foram observadas em 9,7% dos casos. As alterações hepáticas macroscópicas incluíam fígados moderadamente aumentados de volume, mais friáveis, com acentuação do padrão lobular, congestos e com múltiplos focos de necrose pálidos ou hemorrágicos. Películas e filamentos de fibrina cobriam a superfície hepática em 20,4% dos casos e em 27,8% dos casos a parede da vesícula biliar estava espessada por edema. Necrose hepática zonal ou aleatória (93,5% dos casos) associada a corpúsculos de inclusão intranucleares foi a lesão histológica mais regularmente encontrada. Os corpúsculos de inclusão intranucleares ocorreram no fígado em todos os casos e esse foi o critério para confirmação do diagnóstico. As lesões histológicas extra-hepáticas mais importantes incluíram hemorragias e corpúsculos de inclusão em células endoteliais do tufo glomerular renal (50,0%) dos linfonodos (47,8%) , do encéfalo (27,8%), das tonsilas (25,0%) e do baço (10,0%).

Microscopical Lesions and Antigen Distribution in Bovine Fetal Tissues and Placentae Following Experimental Infection with Bovine Herpesvirus-1 during Pregnancy

As part of a larger investigation, gross and histopathological examinations were carried out on six aborted and one non-viable calf born to heifers inoculated with bovine herpesvirus-1 (BHV-1) early in the third trimester of pregnancy. Antibody titres in sera collected from the dams confirmed seroconversion following inoculation. Samples of liver, lung, kidney, brain, heart, spleen, hepatic lymph node and placenta were subjected to histopathological examination. Immunohistochemistry for the detection of BHV-1 antigen was performed on liver and placenta from each calf, and on the full range of tissue from three of the six calves. Six dams aborted between 15 and 50 days post-inoculation (dpi) whilst one produced a live but non-viable calf at 51dpi. Consistent microscopical findings in tissues from the six aborted calves were multifocal coagulative necrosis in the liver and necrotic placentitis. The latter was characterized by villous necrosis, necrosis of vascular endothelium and infiltration of necrotic villi by mixed inflammatory cells. Other findings included multifocal necrosis in kidney, spleen and hepatic lymph node as well as haemorrhage in the lung and kidney. Immunohistochemistry confirmed the presence of BHV-1 antigen in association with these lesions and also revealed focal labelling of the endothelium of small blood vessels and surrounding glial processes in the brains of three calves. Virus isolation confirmed the presence of BHV-1 in the placentae from the six aborted calves and in pooled tissues of three of the fetuses. It is concluded that the pathogenesis of BHV-1 abortion involves infection of vascular endothelial cells in multiple tissues including placenta and brain. Furthermore, histopathological examination in suspected cases of BHV-1 abortion should include placenta as well as fetal viscera, and immunohistochemistry is a valuable tool for confirming a diagnosis of infection with the virus.

ENDOSCOPIC ULTRASOUND OF THE CANINE ABDOMEN

The aim of this study was to develop a standardized procedure for examination of the canine abdomen using endoscopic ultrasound and to describe the organs and structures that could be identified transgastrically. The abdomen of four healthy dogs and two cadavers were examined with endoscopic ultrasound. Five anatomic landmarks were used for standardized imaging of the cranial abdomen. These were the portal vein, splenic head and body, duodenum, left kidney, and aorta. High-resolution images of the following organs and structures could be made: distal esophagus, gastric wall from the cardia to the pylorus, liver, caudal vena cava, hepatic lymph nodes, liver hilus, and associated vessels, trifurcation of the celiac artery as well as the path of its branches and the left pancreatic limb and body. Structures that were more difficult to image were the distal duodenum and right pancreatic limb, the entire jejunum, ileum, and cecum as well as the tail of the spleen. Endoscopic ultrasound allowed excellent visualization of the gastric wall and regional structures without interference with gas artefacts. Centrally located organs such as the pancreas could be well examined transgastrically with endoscopic ultrasound without interference by overlying intestinal segments as is common with transabdominal ultrasound.

Significance of Common Hepatic Artery Lymph Node Metastases During Pancreaticoduodenectomy for Pancreatic Head Adenocarcinoma

Common hepatic artery lymph nodes (CHALN) are frequently sampled during pancreaticoduodenectomy for adenocarcinomas of the head of the pancreas. In some institutions, if metastatic disease is detected intraoperatively in these lymph nodes, the tumor is considered unresectable and a curative operation is not performed. No solid data exist to support this practice. A retrospective review of a prospectively collected database was conducted of the records of all patients who underwent a pancreaticoduodenectomy for pancreatic adenocarcinoma between September 1991 and April 2005. Clinical and pathologic factors were analyzed to determine their influence on survival. Fifty-five of 175 patients had CHALN separately identified and evaluated; these patients constituted the study population. Thirty-eight patients (69%) had one or more lymph nodes with metastatic involvement; 10 of these had disease in CHALN. The median overall survival for patients with node-negative, node-positive (but CHALN-negative), and CHALN-positive disease were 22.9, 16.1, and 14.7 months, respectively. The 5-year overall survival rates for the respective groups were 22%, 17%, and 0%. CHALN metastases correlate with poor prognosis and no long-term survival. Further studies examining CHALN status are indicated and could lead to modifications of pancreatic cancer staging and management.

Migration of intradermally injected quantum dots to sentinel organs in mice.

Topical exposure to nanoscale materials is likely from a variety of sources including sunscreens and cosmetics. Because the in vivo disposition of nanoscale materials is not well understood, we have evaluated the distribution of quantum dots (QDs) following intradermal injection into female SKH-1 hairless mice as a model system for determining tissue localization following intradermal infiltration. The QD (CdSe core, CdS capped, poly[ethylene glycol] coated, 37 nm diameter, 621 nm fluorescence emission) were injected intradermally (ID) on the right dorsal flank. Within minutes following intradermal injection, the highly UV fluorescent QD could be observed moving from the injection sites apparently through the lymphatic duct system to regional lymph nodes. Residual fluorescent QD remained at the site of injection until necropsy at 24 h. Quantification of cadmium and selenium levels after 0, 4, 8, 12, or 24 h in multiple tissues, using inductively coupled plasma mass spectrometry (ICP-MS), showed a time-dependent loss of cadmium from the injection site, and accumulation in the liver, regional draining lymph nodes, kidney, spleen, and hepatic lymph node. Fluorescence microscopy corroborated the ICP-MS results regarding the tissue distribution of QD. The results indicated that (1) ID injected nanoscale QD remained as a deposit in skin and penetrated the surrounding viable subcutis, (2) QD were distributed to draining lymph nodes through the sc lymphatics and to the liver and other organs, and (3) sentinel organs are effective locations for monitoring transdermal penetration of nanoscale materials into animals.

Immunohistochemical study of the local immune response in lambs experimentally infected with Dicrocoelium dendriticum (Digenea)

Phenotypic expression of inflammatory cells in liver and hepatic lymph nodes (HLN) has been examined in lambs experimentally infected with Dicrocoelium dendriticum using immunohistochemical techniques. Thirty-two lambs, 12 infected with 1,000 D. dendriticum metacercariae, 12 with 3,000, and 8 controls were used. Half the lambs in each group were slaughtered on days 60 and 180 post-infection (p.i.), respectively. Primary antibodies (Abs) against T cell epitopes (CD3+, CD4+, CD8+ and WC1+ gammadelta), B cell epitopes (CD79alphacy+, CD45R+), immunoglobulin (IgG)-bearing plasma cells, macrophages (CD14+, VPM32+) and major histocompatibility complex (MHC) class IIbeta antigen were used. T lymphocytes (CD3+, CD4+ and CD8+) and B lymphocytes (CD79alphacy+ and CD45R+) with diffuse pattern or forming lymphoid aggregates and follicles surrounded the septal bile ducts (SBD) and inter-lobular bile ducts, whereas the WC1 gammadelta T cells were scattered. Numerous IgG+ plasma cells were observed around SBD. CD14 and VPM32+ macrophages intermingled with lymphocytes were immunostained by the anti-MHC class IIbeta. This Ab also reacted with lymphoid cells. Likewise, increased positive immunostaining for all Abs used was observed in the HLN of infected lambs. There was no qualitative difference regarding the phenotype expression of inflammatory cells between the lambs infected with D. dendriticum. The humoral and cell-mediated local immune responses observed were similar in the two groups of lambs infected with different doses.

Detection and Management of Extrahepatic Colorectal Cancer in Patients with Resectable Liver Metastases

The presence of extrahepatic disease has a great effect on the management of patients with metastatic colorectal cancer in the liver. FDG-PET scanning is currently the most sensitive way of detecting extrahepatic metastases in such patients. This is supported by 10 studies, which show that FDG-PET scan will discover extrahepatic disease in about one in six patients who have completed standard imaging. Staging laparoscopy is another means of detecting extrahepatic disease. Its role remains undefined especially in patients who have had FDG-PET scans. It should probably be restricted to patients with high clinical risk scores. In terms of treatment, patients with recurrence at the primary colorectal site as well as resectable liver metastases appear to benefit from resection of both sites provided that R0 resections can be obtained. Resection of involved hepatic pedicle lymph nodes in patients with resectable liver metastases is associated with poor outcome. The situation regarding patients with peritoneal and liver metastases bears a strong resemblance to that of primary site recurrence and liver metastases. Very acceptable survival can be expected if the peritoneal disease can be eradicated. Information regarding treatment of lung and liver metastases is the most complete of any of these areas. Good results may be expected if all the disease can be cleared. Caution is required in interpreting claims of good survival when study numbers are small and confidence intervals of data are not provided.

Simplified Staging System for Predicting the Prognosis of Patients With Resectable Liver Metastasis

Although several staging systems for colorectal liver metastasis have been proposed, simple and generally accepted staging systems are not available for this disease. We hypothesized that more detailed analysis of primary colorectal cancer may make it possible to develop a simple staging system and that its stratification ability may be demonstrated by validation against data from unrelated patients. Retrospective analysis of prospectively documented data, development of a stage, and validation against an unrelated cohort. Four tertiary referral centers. Twenty-two clinicopathologic factors were examined in 369 consecutive patients who underwent curative resection for liver metastasis from colorectal cancer (original cohort). Using the independent prognostic factors, a simplified staging system was developed and was validated by data from 229 unrelated patients (validation cohort). Kaplan-Meier survival curve analyses between different prognostic groups in the cohorts. Multivariate analysis revealed several independent prognostic variables, including hepatic lymph node metastasis (relative risk 4.39), 4 or more colorectal lymph node metastases (RR 1.50), carcinoembryonic antigen level of 50 ng/mL or higher (RR 1.29), and multiple hepatic metastases (RR 1.27). Patients with hepatic lymph node metastasis were assigned to stage 4, and the remaining patients were divided according to number of factors: none, stage 1; 1, stage 2; 2 or 3, stage 3. In the original cohort, median survival in stages 1, 2, 3, and 4 was 7.2, 3.5, 2.0, and 1.3 years, respectively. In the validation cohort, these values were 9.6, 4.1, 2.8, and 1.6 years, respectively. The proposed simplified staging system was easy to use, was highly predictive of patient outcome, and permitted categorization of patients into treatment groups. Although we validated this staging system, further validation and improvements are needed.

大腸癌同時性肝転移症例における肝所属リンパ節転移状況

目的 : 大腸癌同時性肝転移の肝所属リンパ節 (HN) 転移について検討し, 治療上の意義について考察した. 対象・方法 : 原発巣に対し, D2・D3郭清をともなう切除が行われた大腸癌同時性肝転移のうち, HNのサンプリングあるいは郭清が行われた54例 (肝切除16例を含む) のHN転移頻度と臨床病理学的諸因子との関連を検討した. 結果 : 肝切除例の3例 (19%), 肝転移非切除例の10例 (26%) にHN転移を認めた. HN転移陽性例は陰性例より肝切除例ではCA19-9が有意に高く (p=0.01), 原発巣のリンパ節転移個数も多い傾向を認め (p=0.09), 一方, 肝切除不能例ではCEAが有意に高かった (p=0.04). 肝転移体積を含め, その他の臨床病理学的諸因子とHN転移の有無の間には関連性は認めなかった. 結語 : 大腸癌同時性肝転移症例の治療法の選択にあたり, 切除・非切除にかかわらず, 臨床的に無視できない頻度のHN転移があることを念頭におき, 実際の診療にあたるべきである.

Overexpression of the cholesterol-binding protein MLN64 induces liver damage in the mouse

To examine the in vivo phenotype associated with hepatic metastatic lymph node 64 (MLN64) over-expression. Recombinant-adenovirus-mediated MLN64 gene transfer was used to overexpress MLN64 in the livers of C57BL/6 mice. We measured the effects of MLN64 overexpression on hepatic cholesterol content, bile flow, biliary lipid secretion and apoptosis markers. For in vitro studies cultured CHO cells with transient MLN64 overexpression were utilized and apoptosis by TUNEL assay was measured. Livers from Ad.MLN64-infected mice exhibited early onset of liver damage and apoptosis. This response correlated with increases in liver cholesterol content and biliary bile acid concentration, and impaired bile flow. We investigated whether liver MLN64 expression could be modulated in a murine model of hepatic injury. We found increased hepatic MLN64 mRNA and protein levels in mice with chenodeoxycholic acid-induced liver damage. In addition, cultured CHO cells with transient MLN64 overexpression showed increased apoptosis. In summary, hepatic MLN64 over-expression induced damage and apoptosis in murine livers and altered cholesterol metabolism. Further studies are required to elucidate the relevance of these findings under physiologic and disease conditions.

Detection of sentinel nodes by a novel red‐fluorescent dye, ATX‐S10Na (II), in an orthotopic xenograft rat model of human gastric carcinoma

We developed a new imaging system to detect sentinel nodes (SNs) using a novel fluorescent tracer, ATX-S10Na(II), and investigated its usefulness in an animal model. Human gastric carcinoma cells were implanted orthotopically into nude rats. ATX-S10Na(II) was injected subserosally into the primary tumor lesion, and visualized by a fluorescence spectro-laparoscope. Presence of tumor cells in lymph nodes (LNs) was determined by RT-PCR specific for human beta-actin. Injection of ATX-S10Na(II) was successful in 27 tumor-bearing rats. A red fluorescence was incorporated into the left gastric and hepatic LNs in 25 and 2 rats, respectively. Of note, human beta-actin was detected in most of these LNs. Fluorescence was not detected in LNs that did not contain cancer. ATX-S10Na(II) is useful for the detection of cancer-containing SNs in an animal model of gastric carcinoma, and may serve as a novel tracer in SN navigation surgery.

Colangiocarcinoma periférico: resultados del tratamiento quirúrgico

Peripheral cholangiocarcinoma (PC) is an uncommon primary hepatic tumor that represents 10% of hepatic resections for primary malignant tumors in our experience. From 1988 to 2004, 29 patients with a diagnosis of PC were treated in our unit. One patient was treated with chemoembolization and the remainder underwent surgery. In 7 patients, hepatectomy was not performed due to the presence of an extrahepatic tumor or massive hepatic invasion. The resectability index was 75%. Twenty-one patients underwent radical excision of PC and comprised the study group. The mean age was 60 years with a slight predominance of women. Sixty-two patients were symptomatic and tumoral markers were elevated in 58%. PC developed in normal liver in 15 patients, in cirrhotic liver in 2 patients and in the context of chronic hepatitis in 4 patients. The mean tumoral size was 7 cm (between 1.6 and 13 cm). Multiple tumors were found in 3 patients, invasion of the hepatic hilum lymph nodes was found in 8 patients and vascular invasion was observed in a further 8 patients. Major hepatectomy was performed in 90% of the patients; radical lymphadenectomy of the hepatic hilum was performed in 15 patients and excision of the extrahepatic biliary tract followed by Roux-en-Y hepaticojejunostomy in 4 patients. Operative mortality occurred in 3 patients (14%); one cirrhotic patient died 4 days after surgery from cardiovascular causes and 2 patients died from liver failure after extensive hepatectomies that included resection of the inferior vena cava and suprahepatic veins. Complications occurred in 33% of the patients. Ten patients (47%) died. Of these, 6 died from tumoral recurrence. Tumoral recurrence occurred in 9 patients (5 hepatic and 4 extrahepatic). Hepatic recurrences were treated with radiofrequency ablation in 2 patients and chemotherapy in 5 patients. The median survival was 11 months. Actuarial survival at 1, 3 and 5 years was 60%, 47% and 47% respectively. Disease-free survival at 1, 3 and 5 years was 50%, 31% and 31% respectively. In univariate analysis, significant risk factors for mortality were lymphatic invasion and a resection margin of less than 1 cm. In multivariate analysis, negative factors for tumoral recurrence were lymphatic invasion, satellitosis, and poor tumoral delimitation. Surgical treatment of PC through radical hepatic resection with margins of more than 1 cm in patients without nodal invasion provides good results with a 5-year survival of 79%.

Operative approach to gallbladder cancer

In most Western countries gallbladder cancer is a rare tumor with a poor prognosis. The majority of patients present with advanced-stage tumors (stage IV) that are not amenable to surgical resection. At the other end of the spectrum a small percentage of patients present with stage I disease that may be cured by cholecystectomy. The role for surgery in patients with stage II and III disease remains controversial, but most hepatobiliary surgeons believe that an aggressive surgical approach improves survival for these patients. However, the extent of hepatic and lymph node resection, the need for resection of the extrahepatic ducts in nonjaundiced patients, the role of vascular resection, and the advisability of hepatopancreatoduodenectomy remain a matter of debate. Although no data from prospective, randomized studies are available, resection of the gallbladder and adjacent liver with or without the extrahepatic bile ducts and with a regional lymph node dissection is the operative approach recommended for selected patients with gallbladder cancer.

Intra-uterine transmission of paratuberculosis (Johne's disease) in farmed red deer

AIM: To determine whether intra-uterine transmission of paratuberculosis (Johne's disease) occurs in farmed red deer (Cervus elaphus) in New Zealand. METHODS: On four different farms, nine late-stage pregnant hinds with Johne's disease were slaughtered and samples were taken from them and their 10 fetuses. Samples of the hepatic, ileocaecal and mesenteric lymph nodes and the posterior ileum were collected from the hinds. The lung, liver, spleen, jejunum and ileum from the fetuses were sampled, as were the placentomes. Blood samples were tested using the ‘Paralisa’ test, a modified immunoglobulin G1 (IgG1) enzyme-linked immunosorbent assay (ELISA). Tissue samples were cultured using the BACTEC system, and fixed samples were sectioned and histological slides examined. RESULTS: All nine hinds and 9/10 fetuses (one hind had twins) were culture-positive for Mycobacterium avium subsp paratuberculosis (M. ptb). Six hinds had gross lesions of Johne's disease, while all hinds had characteristic histopathological lesions affecting the ileum, ileocaecal valve and associated lymph nodes. The only histopathological change observed in the fetuses was some mild inflammation in the lungs of one individual. Acid fast organisms (AFOs) were seen in histological sections of the lymph nodes and ileum of six hinds, and none were seen in tissues from the fetuses. These six hinds were Paralisa-positive, whereas the remaining hinds and fetuses were serologically-negative. CONCLUSIONS: These results confirm that there is a high risk of transmission of M. ptb from clinically affected hinds to their fetuses during pregnancy. CLINICAL RELEVANCE: Johne's disease is an increasingly important disease responsible for deaths in young red deer. Recognising the influence of intra-uterine transmission on the spread of this disease may be an important step towards improved control of Johne's disease.

Aberrant composition of the dendritic cell population in hepatic lymph nodes of patients with hepatocellular carcinoma

Patients with hepatocellular carcinoma (HCC) are characterized by a weak T-cell response to their tumor, and chronic carriers of hepatitis B virus or hepatitis C virus have a poor T-cell response against the virus. These inadequate T-cell responses may be due to insufficient activation of the T cells by dendritic cells (DCs). Because lymph nodes (LNs) are the primary site of antigen-specific T-cell activation, we hypothesized that hepatic LNs of patients with HCC and/or chronic viral hepatitis might have aberrant compositions of their DC populations. To address this hypothesis, we enumerated mature myeloid DCs (MDCs) and plasmacytoid DCs (PDCs) in hepatic LNs by quantitative immunohistochemistry. Patients with HCC and chronic viral hepatitis and patients with chronic viral hepatitis without HCC were compared with patients with liver inflammation of nonviral etiology and with organ donors with healthy livers. The numbers of PDCs and mature MDCs in hepatic LNs of patients with chronic viral hepatitis did not differ from those of patients with liver inflammation of nonviral etiology nor from individuals with healthy livers. However, hepatic LNs of patients with HBV or HCV infection complicated by HCC showed a 1.5-fold reduction in numbers of mature MDCs and a 4-fold increase in numbers of PDCs in their T-cell areas compared with those of patients with viral hepatitis only (P <.01). In conclusion, patients with HCC have an aberrant composition of the DC population in their hepatic LNs. This may be one of the causes of the inadequate T-cell response against HCC in these patients.

Characterization of human liver dendritic cells in liver grafts and perfusates

It is generally accepted that donor myeloid dendritic cells (MDC) are the main instigators of acute rejection after organ transplantation. The aim of the present study was to characterize MDC in human donor livers using liver grafts and perfusates as a source. Perfusates were collected during ex vivo vascular perfusion of liver grafts pretransplantation. MDC, visualized in wedge biopsies by immunohistochemistry with anti-BDCA-1 monoclonal antibody (mAb), were predominantly observed in the portal fields. Liver MDC, isolated from liver wedge biopsies, had an immature phenotype with a low expression of CD80 and CD83. Perfusates were collected from 20 grafts; perfusate mononuclear cells (MNC) contained 1.5% (range, 0.3-6.6%) MDC with a viability of 97 +/- 2%. Perfusates were a rich source of hepatic MDC since 0.9 x 10(6) (range, 0.11-4.5 x 10(6)) MDC detached from donor livers during vascular perfusion pretransplantation. Perfusate MDC were used to further characterize hepatic MDC. Perfusate MDC expressed less DC-LAMP (P = 0.000), CD80 (P = 0.000), CD86 (P = 0.003), and CCR7 (P = 0.014) than mature hepatic lymph node (LN) MDC, and similar CD86 (P = 0.140) and CCR7 (P = 0.262) as and more DC-LAMP (P = 0.007) and CD80 (P = 0.002) than immature blood MDC. Perfusate MDC differed from blood MDC in producing significantly higher amounts of interleukin (IL)-10 in response to lipopolysaccharide (LPS), and in being able to stimulate allogeneic T-cell proliferation. In conclusion, human donor livers contain exclusively immature MDC that detach in high numbers from the liver graft during pretransplantation perfusion. These viable MDC have the capacity to stimulate allogeneic T-cells, and thus may represent a major player in the induction of acute rejection.