Asp68His mutation in the A1 domain of human factor V causes impaired secretion and ineffective translocation.

Congenital factor V (FV) deficiency is a rare inherited disorder. We determined the mechanism of a missense mutation, Asp68His, in the A1 domain of the FV protein, is associated with severe FV deficiency. We characterized the mutant FV-Asp68His protein using in vitro expression studies by using specific secretion and degradation pathway inhibitors and analysed the intracellular translocation of the mutant protein by immunofluorescence staining. The Asp68His mutation caused very low levels of FV protein in the conditioned media, with normal specific FV activity. Similar mRNA degradation rates between FV-wild-type (wt) and FV-Asp68His mRNA showed that the Asp68His mutation does not affect FV expression at the transcriptional level. A specific secretion pathway inhibitor, brefeldin A, was used to demonstrate that the lower efficiency of transport to the outside of the cell for FV-Asp68His mutant protein compared with that of the FV-wt protein. Furthermore, we showed that the Asp68His mutation resulted in increased intracellular degradation through a MG132-mediated proteasomal degradation pathway. In the transfected cell lysates, FV-wt protein had multiple posttranslational modified forms, but the FV-Asp68His protein was not completely glycosylated. We further observed that the FV-Asp68His protein was retrieved in the endoplasmic reticulum only and did not undergo transport to the Golgi apparatus, leading to impaired secretion. These results strongly suggest that the Asp68His mutation may result in intracellular defective trafficking and enhanced degradation, and impaired secretion of FV protein.

Vascular stents in the management of portal venous complications in living donor liver transplantation.

To evaluate the efficacy of stent placement in the treatment of portal vein (PV) stenosis or occlusion in living donor liver transplant (LDLT) recipients, 468 LDLT records were reviewed. Sixteen (10 PV occlusions and 6 stenoses) recipients (age range, 8 months-59 years) were referred for possible interventional angioplasty (dilatation and/or stent) procedures. Stent placement was attempted in all. The approaches used were percutaneous transhepatic (n = 10), percutaneous transsplenic (n = 4), and intraoperative (n = 2). Technical success was achieved in 11 of 16 patients (68.8%). The sizes of the stents used varied from 7 mm to 10 mm in diameter. In the five unsuccessful patients, long-term complete occlusion of the PV with cavernous transformation precluded catherterization. The mean follow-up was 12 months (range, 3-24). The PV stent patency rate was 90.9% (10/11). Rethrombosis and occlusion of the stent and PV occurred in a single recipient who had a cryoperserved vascular graft to reconstruct the PV during the LDLT operation. PV occlusion of >1 year with cavernous transformation seemed to be a factor causing technical failure. In conclusion, early treatment of PV stenosis and occlusion by stenting is an effective treatment in LDLT. Percutaneous transhepatic and transsplenic, and intraoperative techniques are effective approaches depending on the situation.

Liver graft regeneration in right lobe adult living donor liver transplantation.

Optimal portal flow is one of the essentials in adequate liver function, graft regeneration and outcome of the graft after right lobe adult living donor liver transplantation (ALDLT). The relations among factors that cause sufficient liver graft regeneration are still unclear. The aim of this study is to evaluate the potential predisposing factors that encourage liver graft regeneration after ALDLT. The study population consisted of right lobe ALDLT recipients from Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan. The records, preoperative images, postoperative Doppler ultrasound evaluation and computed tomography studies performed 6 months after transplant were reviewed. The volume of the graft 6 months after transplant divided by the standard liver volume was calculated as the regeneration ratio. The predisposing risk factors were compiled from statistical analyses and included age, recipient body weight, native liver disease, spleen size before transplant, patency of the hepatic venous graft, graft weight-to-recipient weight ratio (GRWR), posttransplant portal flow, vascular and biliary complications and rejection. One hundred forty-five recipients were enrolled in this study. The liver graft regeneration ratio was 91.2 +/- 12.6% (range, 58-151). The size of the spleen (p = 0.00015), total portal flow and GRWR (p = 0.005) were linearly correlated with the regeneration rate. Patency of the hepatic venous tributary reconstructed was positively correlated to graft regeneration and was statistically significant (p = 0.017). Splenic artery ligation was advantageous to promote liver regeneration in specific cases but splenectomy did not show any positive advantage. Spleen size is a major factor contributing to portal flow and may directly trigger regeneration after transplant. Control of sufficient portal flow and adequate hepatic outflow are important factors in graft regeneration.

Plasma exchange therapy for thrombotic thrombocytopenic purpura in pediatric patients with liver transplantation.

PURPOSE: Sporadic cases of thrombotic thrombocytopenic purpura (TTP) have been reported in bone marrow and solid organ transplant patients receiving cyclosporine (CsA). We reported our experience with TTP using plasma exchange (PE) therapy in patients with liver transplantation (OLT). METHODS: Between March, 1993, and May, 2007, 400 patients underwent OLT, including 146 pediatric living-donor liver transplantation (LDLT). Four pediatric patients developed TTP after OLT: three were males and one female of mean age at the time of transplantation of 7.8 +/- 3.6 years. The four recipients had the following indications for OLT: two glycogen storage disease, one biliary atresia, and one fulminant hepatic failure. Four patients initially received triple drug immunosuppression consisting of CsA, azathioprine, and steroids. RESULTS: Four (1%) patients developed TTP after OLT. All four patients were pediatric in the age group. The mean age at the time of TTP diagnosis was 8.0 +/- 3.2 years, with a mean postoperative interval to TTP of 78.8 +/- 114.2 days. The mean baseline platelet count was 7.0 +/- 7.1 x 10,000. The eventual platelet count was 21.1 +/- 20.8 x 10,000 after PE. These patients received PE 6.0 +/- 4.2. The mean baseline serum creatinine was 0.8 +/- 0.8 mg/dL. The mean peak serum creatinine was 2.3 +/- 2.3 mg/dL. The mean serum CsA level was 717.5 +/- 106.0 ng/mL before TTP diagnosis. Four patients were diagnosed by blood peripheral smears. The causes of TTP were CsA-associated in three patients and venoocclusive disease (VOD) in one patient. Three patients improved their platelet counts after PE therapy. Two patient changed from CsA to FK 506, one underwent reduced CsA dosage, and one stopped CsA. Three patients died of recurrent VOD, infection, and intrapulmonary hemorrhage. Only one patient survived. CONCLUSIONS: The incidence of TTP in our series was lower. It only developed in pediatric patients. The causes of TTP were associated with CsA and/or VOD. The mortality was high after the TTP diagnosis. We concluded that TTP was a potentially fatal condition, but an early diagnosis with prompt institution of therapy with invasive PE therapy may reduce its mortal consequences.

The reaction of posttransplant denervated liver on the hemorrhagic shock in rats.

OBJECTIVE: The aims of the study were to determine the effects of denervation on the function of the liver transplantation as a blood reservoir and to define its vulnerability to ischemic-reperfusion (I/R) injury after hemorrhagic shock. MATERIALS AND METHODS: Hemorrhagic shock with a mean arterial blood pressure (MAP) of 40 to 50 mm Hg was induced by withdrawing blood at a rate of approximately 1 mL/min among 10 posttransplant denervated rats and 10 sham rats for 1 hour. The rats were then resuscitated by retransfusing the drawn blood with sacrifice under deep anesthesia at 1 hour after resuscitation. The total amount of blood required to achieve hemorrhagic shock was compared between groups as well as the vulnerability and reactions of the posttransplant denervated liver to I/R injury after hemorrhagic shock as assessed by gene expressions of c-jun, c-fos, tumor necrosis factor (TNF)-alpha, interleukin (IL)6, IL-10, and heat-shock protein 70 (HSP70). RESULTS: The volume of blood that had to be drawn to reach a MAP of 40 to 50 mm Hg was not significantly different between the groups. One hour of hemorrhagic shock followed by resuscitation resulted in significant increases in the genes expression of c-fos, TNF-alpha, IL-6, IL-10, and HSP70 in comparison to the control values, but no difference was observed between experimental and sham groups. CONCLUSION: We suggest that the function of the liver as a blood reservoir and the gene expressions of c-fos and pro- and anti-inflammatory cytokines, as well as the protective protein HSP70 in response to I/R injury, were not altered by liver transplantation.

Imaging Validation of Drug-Eluting Beads Transarterial Chemoembolization of Hepatocellular Carcinomas in Living Donor Liver Transplantation.

OBJECTIVE: The aim of this study is to determine whether post-transarterial chemoembolization imaging (computed tomography or magnetic resonance imaging) could accurately predict the tumors' necrosis on pathologic specimens. BACKGROUND: Transarterial chemoembolization with drug-eluting beads has been proven to be an effective way to bridge patients with hepatocellular carcinomas to liver transplantation. MATERIALS AND METHODS: From September 2012 to June 2017, 59 patients with a total of 78 hepatocellular carcinomas, who received transarterial chemoembolization with drug-eluting beads before liver transplantation in Kaohsiung Chang Gung Memorial Hospital, were included in the study. All patients and hepatocellular carcinomas have pre-transarterial chemoembolization and post-transarterial chemoembolization images (computed tomography or magnetic resonance imaging) and pathological findings for correlation. Tumor response was evaluated according to modified Response Evaluation Criteria in Solid Tumors. The ranges of necrotic percentage are 100%, 91-99%, 51-90%, and <50%. RESULTS: The accuracy rate between the imaging and pathology correlation was 40% for computed tomography and 42% for magnetic resonance imaging. The recurrent rate of the complete respond group is 11.5%, the partial respond group is 16.0%, and the stationary group is 28.6%. CONCLUSION: Computed tomography and magnetic resonance imaging sensitivity is not satisfactory for microscopic evaluation of residual tumors after transarterial chemoembolization with drug-eluting beads. However, survival is good after liver transplantation no matter what the microscopic findings were.

Regular tai chi chuan exercise enhances functional mobility and CD4CD25 regulatory T cells.

BACKGROUND: The duration and vigour of physical exercise are widely considered to be critical elements that may positively or negatively affect physical health and immune response. OBJECTIVES: To investigate the effect of a 12 week programme of regular tai chi chuan exercise (TCC) on functional mobility, beliefs about benefits of exercise on physical and psychological health, and immune regulation in middle aged volunteers. METHODS: This quasi-experimental research design involving one group with testing before and after the programme was conducted to measure the effect of 12 weeks of TCC exercise in 14 men and 23 women from the normal community. RESULTS: Regular TCC exercise had a highly significant positive effect on functional mobility (p = 0.001) and beliefs about the health benefits of exercise (p = 0.013) in the 37 participants. Total white blood cell and red blood cell count did not change significantly, but a highly significant (p<0.001) decrease in monocyte count occurred. A significant (p = 0.05) increase in the ratio of T helper to suppressor cells (CD4:CD8) was found, along with a significant (p = 0.015) increase in CD4CD25 regulatory T cells. Production of the regulatory T cell mediators transforming growth factor beta and interleukin 10 under specific antigen stimulation (varicella zoster virus) was also significantly increased after this exercise programme. CONCLUSIONS: A 12 week programme of regular TCC exercise enhances functional mobility, personal health expectations, and regulatory T cell function.

Pharmacokinetic Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Distinguishing Hepatocellular Carcinoma From Cholangiocarcinoma in Pre-Liver Transplantation Evaluation.

OBJECTIVE: Liver transplantation for intrahepatic cholangiocarcinoma is notorious for rapid recurrence with poor survival rate postoperatively and has therefore been discontinued in most centers. The purpose of this study is to distinguish hepatocellular carcinoma (HCC) from cholangiocarcinoma in pretransplantation imaging evaluation by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: From January 2014 to September 2015, 19 patients were included in the study, with a mean age of 62.8 years. All subjects underwent pretransplantation DCE-MRI and surgical excision or core biopsy. The DCE-MRI parameters were measured using the Tofts model 1999. Statistical analysis included nonparametric tests and area under the curve for the receiver operating characteristic. RESULTS: Fourteen HCCs and 5 cholangiocarcinomas were diagnosed by surgical pathology. The mean size of tumor was 6.4 cm (range, 1.5 cm to 13.7 cm). All DCE-MRI parameters were calculated as the ratio between the tumor and normal liver parenchyma and K(trans) (1/min) was used as a distinguishing parameter between the two tumors. K(trans) was higher in the cholangiocarcinoma group (1.89 ± 1.13) than in the HCC group (0.46 ± 0.35). Univariate analysis revealed that K(trans) has a high significant difference (P = .001). The optimal K(trans) value cutoffs were 1 or more (area under the curve = 0.971) for detection of HCCs or cholangiocarcinomas. CONCLUSION: The analysis of DCE-MRI with the kinetic model (Tofts, 1999) presents a new and practical approach indiscrimination of HCC from cholangiocarcinoma for pretransplantation imaging evaluation.

Increased plasma concentration of nitric oxide in type 2 diabetes but not in nondiabetic individuals with insulin resistance.

OBJECTIVE: Insulin resistance (IR) is a key element in the pathogenesis of type 2 diabetes. The results of recent experiments on insulin-mediated vasodilatation have suggested that vascular insensitivity is a component of IR. However, it is still controversial that patients with type 2 diabetes have a decreased ability of insulin to increase endothelial nitric oxide (NO) release. METHOD: Plasma concentration of NO was examined in 26 patients with type 2 diabetes and 78 nondiabetic volunteers during an insulin suppression test. The test measured the efficacy of insulin in promoting disposal of the infused glucose load, in which the steady state plasma glucose (SSPG) during the 150-180 min of the test was used as an index of IR. Plasma NO levels were assayed by measurement of the stable end products of their metabolism. Comparison of plasma NO levels between groups were performed by Mann-Whitney test and relationships between SSPG and different variables were analyzed by partial correlations. RESULTS: Our results showed that the plasma NO levels were significantly higher in the diabetic group. When the nondiabetic subjects were analyzed according to their SSPG levels, there was no difference of plasma NO levels between those with SSPG>160 mg/dl and those with SSPG<160 mg/dl. There were also no difference of NO levels between those with a family history of type 2 diabetes and those without. In the nondiabetic group, SSPG correlated with BMI, fasting insulin, triglyceride and HDL-cholesterol, but neither with plasma NO levels nor fasting plasma glucose. CONCLUSION: Our data suggests that the impairment of NO activity in patients with type 2 diabetes is due to an impaired effect rather than its production. This altered NO signaling pathway is not an early event in insulin resistant individuals. Any such changes will not be apparent until type 2 diabetes with overt hyperglycemia develops.

Liver transplantation from an uncontrolled non-heart-beating donor maintained on extracorporeal membrane oxygenation.

Liver transplantation, a definitive treatment for end-stage liver disease, has achieved excellent results. However, potential recipients on the waiting list outnumber donors. To expand the donor pool, marginal grafts from older donors, steatotic livers, and non-heart-beating liver donors (NHBD) have been used for transplantation. Reducing the warm ischemia time of NHBD is the critical factor in organs preservation. Liver transplantation using grafts from NHBD have been reported to display a high incidence of primary graft nonfunction and biliary complications. The authors report a liver graft donor who was maintained on extracorporeal membrane oxygenation (ECMO) after successful cardiopulmonary resuscitation. Core body temperature was 5 degrees C. Procurement of the liver using a rapid flush technique was performed 4 hours after instituting ECMO. Graft function recovered fully after transplantation. In conclusion, ECMO may be used to reduce warm ischemia time in liver grafts obtained from uncontrolled NHBD, thereby increasing graft salvage rates.

Magnetic resonance of the hepatic veins with angular reconstruction: application in living-related liver transplantation.

BACKGROUND: Preoperative mapping of the hepatic venous system of the partial liver graft is indispensable to the success of living-related liver transplantation. We assessed the accuracy of magnetic resonance (MR) venography with angular reconstruction in depicting the tributaries of the middle hepatic vein and left hepatic vein in the donors, which was essential in graft retrieval and venoplasty. METHODS: Nineteen living-related liver transplantation donors underwent a pretransplantation survey, including sonography and MRI for hepatic venous evaluation. T1-weighted images were reconstructed manually, using the inferior vena cava as a fixed point for tilting to produce an oblique plane image where both the middle hepatic vein and left hepatic vein could be demonstrated draining into the inferior vena cava. The reconstructed images of the hepatic veins were compared with preoperative sonography, intraoperative sonography, and operative findings. RESULTS: Preoperative sonography and MR findings correlated well with the operative findings in the major hepatic veins. The MR venography of the ramification of the hepatic veins has an accuracy of 93%, the sonography, 84%. Sonography is slightly inferior in the evaluation of the hepatic vein in segment 4 and the left superior hepatic vein, with an accuracy of 73% and 67%, respectively. CONCLUSION: MR venography with angular reconstruction is accurate in depicting the complex distribution of the hepatic veins of the left liver, providing important information for decision making as to the cutting plane during graft retrieval and the method of venoplasty and anastomosis. Thus, unnecessary blood loss could be avoided and vascular complications could be prevented, as these conditions would be unacceptable for a healthy living donor. We propose that MR venography, a rapid and reliable technique, is an appropriate alternative examination or complementary modality to sonography in the pretransplantation evaluation of the living donor.

Assessment of donor fatty livers for liver transplantation.

AIM: The effect of fatty liver on graft survival, especially with reference to macrovesicular and microvesicular steatosis, is still uncertain. This preliminarily study was designed to create a noninvasive method for the quantification of the hepatic fat content in vivo and to establish provisional criteria for the assessment of fatty donor livers before liver transplantation among transplant surgeons, radiologists, and pathologists. METHODS AND MATERIALS: Different degrees of rat fatty liver model were established by feeding rats a diet deficient in choline and methionine for different periods of time. Computed tomography (CT) with test tubes containing variable percentages of fat equivalent substance were used to assess the severity of fatty change of the rat liver. This was then correlated with the histological classification, level of hepatic enzymes, and graft survival. RESULTS: Linear correlation between the fat volume fraction added to the test tubes and CT density were found. The process of producing a fatty liver via diet alteration peaked at week 3. At this time hepatic enzymes, radiological fat content, and posttransplantation survival were worse (P=0.013), compared with other time points. Radiological assessment of fatty liver correlated well with survival and serum glutamic oxaloacetic transaminase and glutamic pyruvate transaminase levels. CONCLUSION: Severe microvesicular steatosis does not influence recipient survival, however, macrovesicular steatosis affects graft survival. Caliber CT is a practical and simple method that allows an accurate noninvasive quantitative assessment of hepatic fatty infiltration. It has potential to be a useful parameter for the assessment of donor livers for clinical liver transplantation.

Single imaging modality evaluation of living donors in liver transplantation: magnetic resonance imaging.

BACKGROUND: Liver graft size, anatomy of the bile duct and the vascular inflow and outflow are essential for living related liver transplantation (LRLT). Preoperative delineation of those variations that would change the operative procedure to achieve a successful result especially in an emergency condition. PURPOSE: Our aim was to develop a rapid and noninvasive imaging diagnostic method for the detection of anatomical variants that is mandatory for a safe operation when selecting potential liver transplant living donors. We used a different magnetic resonance (MR) imaging technique, which enabled to us to exploit the anatomical landmark of the liver, signal enhancement of blood flow in the abdomen, and the intrahepatic biliary routes inside the liver. Then, with the help of Advantage Window workstation reconstruction, the reconstructed single vascular or biliary systems were displaced in a three-dimensional fashion and the whole examination finished within 30 min. METHODS: Modification of the standard MR technique was performed on a superconductive 1.5T whole body image scanner, MR arteriogaphy, venography, and cholangiography with three-dimensional reconstruction in evaluating the anatomy of the hepatic arteries, hepatic veins, portal venous system, bile ducts, and liver size in potential liver transplant living donors. These anatomical structures were compared with traditional imaging methods. RESULTS: In all 38 cases, as well as delineation of the portal vein detail to the segmental level was satisfactorily obtained in this MR study. The images were well displayed in a three-dimensional fashion, which had good correlation with images from traditional imaging modalities and operative findings. In 86.8% cases, the MR arteriography was well matched with the celiac angiography. Of those 17 operative cases, estimation of liver volume was well correlated with the liver graft within 3.9-12.5% variation. In the major hepatic vein, we obtained 100% accuracy and 88.2% in the minor branches. Of 12 donors received intraoperative cholangiography during liver donation, good correlation of biliary anatomy was achieved. One donor was excluded from graft donation due to the complicated arterial supply to the left liver. According to the anatomical variation, surgical procedures in graft harvesting and anastomosis were readjusted and no major complications were found in those donors and all recipients survived after liver transplantation. CONCLUSION: MR volumetry, venography, angiography, and cholangiography with three-dimensional reconstruction is sufficient for all major imaging evaluation. It may replace the traditional conventional catheter angiography, computed tomography, sonography and endoscopic retrograde cholangiography as a single investigation in the evaluation of the potential liver transplant donors. Angiography is only valuable in suboptimal cases and intraoperative cholangiography is only performed in biliary ductile variants.

Serum levels of matrix metalloproteinase 2 in patients with breast cancer.

Matrix metalloproteinases (MMPs) have been reported to be associated with invasive and metastatic behaviors of human malignant tumors. However, there is still limited knowledge about the role of matrix metalloproteinases-2 (MMP-2) in breast cancer. This study was designed with the aim to elucidate the possible relationship between the preoperative circulating MMP-2 and breast cancer. Fifty-seven consecutive patients with invasive breast cancer undergoing surgery were prospectively included and evaluated. Venous blood samples were collected before the surgery. Sera were obtained by centrifugation, and stored at -70 degrees C until assayed. The control group consisted of 12 patients with benign breast tumor (six with fibrocystic disease and six with fibroadenoma). Serum concentrations of MMP-2 were measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor stage, age, estrogen receptor, lymph node status, and TNM staging were reviewed and recorded. The mean value of serum MMP-2 in patients with invasive breast cancer was 694.3+/-140.5 ng/ml and those of control group were 593.3+/-134.0 ng/ml and the difference was significant (P=0.026). Furthermore, there were significantly higher serum levels of MMP-2 in the patients with more advanced primary tumor staging (P=0.005), in the patients with more advanced lymph node status(P=0.011) and in the patients with more advanced TNM staging (P<0.001). In multivariate analysis, TNM staging (P<0.001) appeared as independent factor regarding the significant higher serum levels of MMP-2. Patients with more advanced TNM staging were shown to have higher serum MMP-2 levels. Thus preoperative serum MMP-2 levels might reflect the severity of invasive breast cancer and deserve further evaluation.

Unusual short rib-polydactyly syndrome.

We present a case of lethal short rib-polydactyly syndrome (SRPS) that cannot be categorized into the existing classification. A nosologic discussion is presented. To our knowledge, situs inversus totalis, as in our case, has not been described before in any SRPS.

Increased incidence of cytomegalovirus but not Chlamydia pneumoniae in atherosclerotic lesions of arteries of lower extremities from patients with diabetes mellitus undergoing amputation.

AIMS: To evaluate the association between cytomegalovirus (CMV) or Chlamydia pneumoniae infection and the development of accelerated atherosclerotic lesions in patients with diabetes who are known to have an impaired immune response to infection and a high incidence of atherosclerosis. METHODS: Two hundred arterial samples from patients with diabetes who had undergone surgical amputation for gangrenous lower limbs were selected to assess the presence of CMV or C pneumoniae nucleic acid by means of the polymerase chain reaction. RESULTS: CMV nucleic acid sequences were detected in 64 of 200 (32%) samples and C pneumoniae in seven of 200 (3.5%) arterial samples with severe atherosclerosis. Of those positive for C pneumoniae, six were also positive for CMV. CONCLUSION: The significantly higher incidence of CMV nucleic acid sequences in the arterial samples of patients with diabetes supports the hypothesis that this organism is involved in the pathogenesis of atherosclerosis in patients with diabetic mellitus. It is possible that the potential role of different infectious agents in the pathogenesis of atherosclerosis might rely on their biological properties and their infectivity in hosts with varying immunological status.

The nodular form of hepatic tuberculosis: a review with five additional new cases.

BACKGROUND: Tuberculosis presenting as an isolated liver tumour, without active pulmonary or miliary tuberculosis, or other clinical evidence of tuberculosis, is distinctly rare. A greater awareness of this rare clinical entity may prevent needless surgical intervention. AIMS: To help characterise this distinctly rare presentation of tuberculosis, five new cases are presented, together with a review of the world literature. The clinical, laboratory, radiological, and pathological features of these patients are described. METHODS: Polymerase chain reaction (PCR) assay of the liver tissue was carried out in all cases to confirm an aetiological diagnosis of Mycobacterium tuberculosis infection. RESULTS: All five patients (44-71 years old; two women, three men) underwent surgery, and had a preoperative diagnosis of malignant hepatic neoplasm and a postoperative histological diagnosis of chronic granulomatous inflammation, suggestive of tuberculosis. None of them had a known previous history of tuberculosis. All of them were positive for M tuberculosis by PCR analysis of the liver tissue. CONCLUSIONS: This report illustrates the difficulty in reaching a correct preoperative diagnosis. It is usually unsuspected and confused with primary or metastatic carcinoma of the liver, especially when it coexists with other malignancies. A high index of suspicion is required for diagnosis, which can be made only by histological and bacteriological studies, and PCR analysis.

Endometrial cyst of the liver: a case report and review of the literature.

The occurrence of pelvic endometriosis is not uncommon but hepatic endometriosis is extremely rare. Only five such cases of hepatic endometriosis have been described in the literature. This report concerns another patient with hepatic endometriosis forming a large cystic mass. The clinicopathological features and the possible pathogenesis are discussed. Endometriosis should be considered in the differential diagnosis of a cystic liver mass, particularly in patients with known endometriosis.

Smooth muscle tumors of the gastrointestinal tract: analysis of prognostic factors.

BACKGROUND: The survival rates and therapeutic approaches to gastrointestinal leiomyoma and leiomyosarcoma vary widely. This review analyzes the clinical symptoms and signs, the results of the pathologic examination, and the DNA makeup of these tumors and determines the factors that affect the prognosis of patients who have leiomyosarcoma. METHODS: Flow cytometric DNA analysis was performed in 80 patients with gastrointestinal smooth muscle tumors to establish the correlation of DNA ploidy with tumor size and stage and histologic grade. Using univariate and multivariate analyses, we investigated tumor size, histologic grade, association with gastrointestinal bleeding, DNA makeup, operative procedure, age, gender, and tumor necrosis as they affect the long-term survival of 45 patients with leiomyosarcoma. The Kaplan-Meier method was used to determine the survival rates and the log-rank method was used to compare survival rates between the two groups. RESULTS: Between 1986 and 1992, operations were performed on the 80 gastrointestinal smooth muscle tumors--esophageal 1, stomach 32, intestinal 33, colonic 2, and rectal 12. The most common symptoms and signs were gastrointestinal bleeding (43.8%), abdominal mass (37.5%), and abdominal pain (21.3%), and the tumors were classified as leiomyoma 35, low-grade leiomyosarcoma 24, and high-grade leiomyosarcoma 21, according to the cellular atypia and mitotic rate. DNA ploidy correlated with histology grade (r = 0.70, p < 0.01) and tumor size (r = 0.31, p < 0.01) but not with localized or advanced tumors. Only one patient with leiomyoma died of liver metastasis during the follow-up period. In univariate analysis of the 45 patients with leiomyosarcoma, the survival rate was poor in men with tumor sizes greater than 5 cm, incomplete resections, advanced tumors, and high-grade tumors. With multivariate Cox regression analysis only advanced tumors (p < 0.01) and high-grade tumors (p < 0.01) were the independent factors that affected survival. CONCLUSIONS: Leiomyosarcomas usually measure more than 10 cm. In univariate analysis the significant factors affecting the survival rate of patients with leiomyosarcoma are maleness, size greater than 5 cm, inadequate resection, and advanced-stage and high-grade disease. In multivariate Cox regression analysis advanced-stage and high-grade leiomyosarcoma are the only independent factors affecting survival. DNA ploidy correlates with the size and the grade of gastrointestinal smooth muscle tumors but not with tumor stage. DNA ploidy does not affect independently the survival of leiomyosarcoma.

An evaluation of the prognostic significance of HLA-DR expression in axillary-node-negative breast cancer.

BACKGROUND: Adjuvant treatment for node-negative breast cancer remains controversial. It is important to pick out the high-risk groups who may benefit from adjuvant systemic therapy and avoid the unnecessary additional therapy for the favorable prognostic groups. METHODS AND MATERIAL: Retrospective study of immunohistochemical staining for HLA-DR on tumor cells from paraffin-embedded tissue specimens of 32 patients with node-negative invasive breast cancer at this hospital from 1986 to 1991 was performed with the aim to investigate its prognostic significance. RESULTS: HLA-DR staining was positive in nine (28%) patients and negative in twenty-three (72%) patients. One (11%) was a recurrence, and no (0%) death occurred in the positive group, compared with nine (39%) recurrences and five (22%) deaths in the negative group. The multivariate analysis failed to show that HLA-DR expression is an independent prognostic factor. However, with univariate analysis, the 5-year disease-free survival rate (87%) of the positive group was significantly better than that (35%) of the negative group (p = 0.04). The 5-year overall survival rate (100%) of the positive group was also better than that (66%) of the negative group, but the difference was not statistically significant. Furthermore, when combination of the HLA-DR expression and estrogen receptor status was used, both the 5-year disease-free and overall survival rate (81% and 100%, respectively) of group A (positive staining for either HLA-DR or estrogen receptor and positive staining for both) were significantly better than those (33% and 58%, respectively) of group B (negative staining for both HLA-DR and estrogen receptor). CONCLUSIONS: We believe HLA-DR expression may be a promising, additive predictive factor to node-negative breast cancer and deserves further investigation based on these preliminary results.