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1.
Pediatr Surg Int ; 36(10): 1243-1247, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32833126

ABSTRACT

INTRODUCTION: Oesophageal atresia ± tracheoesophageal fistula (EA/TEF) associated with congenital heart disease (CHD) carries a worse prognosis than EA/TEF alone. Though the Spitz classification takes major CHD into account, there are no data regarding survival with the specific combination of EA/TEF and Tetralogy of Fallot (TOF). With advances in postnatal care, we hypothesised that, survival is improving in these complex patients. This study reports morbidity and mortality outcomes of newborns with oesophageal atresia and TOF cardiac malformations METHODS: All patients with EA/TEF and TOF treated at Alder Hey Children's Hospital between the years 2000-2020, were identified. Data sets regarding gestation, birth weight, associated anomalies, operative intervention, morbidity, and mortality were analysed. RESULTS: Of a total of 350, EA/TEF patients 9 (2.6%) cases had EA/TEF associated with TOF (M:F 4:5). The median gestational age was 35/40 (range 28-41 weeks) with a median birth weight of 1790 g (range 1060-3350 g). Overall survival was 56% (5/9 cases) and all survivors remain under follow up (range 37-4458 days). Surgical strategies for managing EA/TEF with Fallot's tetralogy included 6/9 primary repairs and 3/9 cases with TEF ligation only (+ gastrostomy ± oesophagostomy). CONCLUSIONS: This study reports outcome data from one of the largest series of EA TEF patients with Fallot's tetralogy. Whilst outcomes may be challenging for this unique patient cohort, survival metrics provide important prognostic information that can be widely shared with health care teams and parents.


Subject(s)
Esophageal Atresia/mortality , Forecasting , Hospitals, Pediatric/statistics & numerical data , Tracheoesophageal Fistula/mortality , Esophageal Atresia/diagnosis , Female , Follow-Up Studies , Humans , Infant , Infant Mortality/trends , Infant, Newborn , Male , Prognosis , Retrospective Studies , Survival Rate/trends , Tetralogy of Fallot/diagnosis , Tetralogy of Fallot/mortality , Tracheoesophageal Fistula/diagnosis , United Kingdom/epidemiology
2.
Transplant Proc ; 48(3): 924-8, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27234769

ABSTRACT

BACKGROUND: Polyomavirus BK-associated nephropathy (BKVN) has been a serious problem after kidney transplantation. Detection of urinary decoy cells (UDCs) and assessment of polyomavirus BK nucleic acids by polymerase chain reactions (PCRs) are currently used, noninvasive tests. PCRs have better positive predictive value (PPV) but higher cost and lower accessibility. This study investigated ways to improve the PPV of UDCs for BKVN prediction. METHODS: From 2000 to 2013, kidney transplant recipients with sustained UDCs for more than half a month and who had received allograft biopsies were enrolled. We analyzed the PPV of UDCs for BKVN with 2 variables: (i) the percentage changes in serum creatinine (SCr) levels and (ii) the duration of sustained UDCs by receiver operating characteristic (ROC) curve analysis; we predicted the percentage changes in SCr levels with the corresponding PPV using a linear regression model. RESULTS: BKVN was diagnosed in 26 of 68 enrolled patients. The percentage changes in SCr levels significantly deteriorated in the BKVN group during 1-2 months of UDC positivity. According to ROC curve analysis, percentage changes in SCr levels had a significant discriminating power for BKVN during 1-1.5 month, and if the percentage changes in SCr levels were >19%, the PPV of UDCs for BKVN was 50%. CONCLUSIONS: An UDC surveillance program is a judicious strategy to predict BKVN in kidney transplant patients, particularly when graft renal function shows deterioration after 1 month of UDC positivity.


Subject(s)
BK Virus/isolation & purification , Kidney Diseases/pathology , Kidney Diseases/virology , Kidney Transplantation , Polyomavirus Infections/pathology , Adolescent , Adult , Aged , Creatinine/blood , Female , Humans , Kidney Diseases/surgery , Male , Middle Aged , Polymerase Chain Reaction , Predictive Value of Tests , ROC Curve , Retrospective Studies , Urinalysis , Urine/cytology , Urine/virology , Young Adult
4.
Transplant Proc ; 42(9): 3382-6, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21094783

ABSTRACT

BACKGROUND: Deceased-donor kidney transplantation (DDKT) from high-terminal creatinine donors is associated with lower graft survival. These kidneys may be considered for discarding, worsening the organ shortage crisis. Using time-zero biopsy for histologic evaluation of these kidneys, we identified those organs eligible for transplantation, seeking to achieve better graft utility with comparable outcomes. METHODS: From April 2004 to April 2008, 55 patients underwent DDKT. A time-zero biopsy was used to examine glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriolar narrowing. A scoring system was used to determine a discard. RESULTS: Twenty-five patients received DDKT from donors whose terminal creatinine levels were >2.0 mg/dL (high terminal creatinine, HTC group) and 30 from donors whose terminal creatinine levels were <2.0 mg/dL (low terminal creatinine, LTC group). Patients who accepted kidneys from HTC donors had shorter waiting times (P = .011) but a higher incidence of delayed graft function after transplantation (P < .001). Nonetheless, 5-year graft survival rates were similar between the two groups. CONCLUSIONS: With a time-zero biopsy for histologic evaluation, kidneys recovered from high-terminal creatinine donors can be transplanted to overcome the organ shortage while achieving reasonable graft survival.


Subject(s)
Creatinine/blood , Donor Selection , Graft Survival , Kidney Transplantation , Kidney , Tissue Donors/supply & distribution , Adult , Biomarkers/blood , Biopsy , Delayed Graft Function/etiology , Graft Rejection/etiology , Humans , Kidney/pathology , Kidney/physiopathology , Kidney/surgery , Kidney Transplantation/adverse effects , Middle Aged , Predictive Value of Tests , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Risk Factors , Taiwan , Time Factors , Treatment Outcome , Waiting Lists , Young Adult
5.
Transplant Proc ; 40(7): 2097-9, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18790163

ABSTRACT

BACKGROUND: The organ shortage and high prevalence of hepatitis B (HB) infection in the general population are important issues in Taiwan. It is difficult for us to abandon HBsAg(+) donors. Hereby we present our experience transplanting kidneys from deceased donors with HB virus infection. METHODS: From November 1977 to March 2007, 21 patients with end-stage renal disease received kidney grafts from 12 HBsAg(+) deceased donors (3.92% of 306 donors). One of the 12 donors was hepatitis Be antigen (HBeAg) (+), and 5 displayed antibody to hepatitis core antigen (anti-HBc) (+). Four of the 21 recipients were HBsAg(+) before transplantation. RESULTS: Four HBsAg(+) recipients remained surface antigen positive after transplantation. One of them died of an intracranial hemorrhage. Two (11.76%) of the other 17 HBsAg(-) recipients became HBsAg(+), 1 of whom died of hepatic failure and the other of sepsis. The other 15 HBsAg(-) recipients (88.23%) remained HBsAg(-) after transplantation. They displayed normal serum levels of aspartate aminotransferase/alanine aminotransferase during the follow-up period. The 5-year patient and graft survivals were 85.15% and 61.14%, respectively. CONCLUSION: Although the number of patients is relatively small, it does suggest that a kidney allograft from an HBsAg(+) deceased donor transplanted to an HBsAg(+) or (-) recipient is safe. This strategy shortens the waiting time. Additional prophylactic HB immunoglobulin and antiviral medications are also suggested. Frequent surveillance after transplantation is essential.


Subject(s)
Hepatitis B Surface Antigens/analysis , Kidney Failure, Chronic/surgery , Kidney Transplantation/statistics & numerical data , Tissue Donors/statistics & numerical data , Adolescent , Adult , Cadaver , Child , Female , Graft Rejection/immunology , Humans , Kidney Failure, Chronic/immunology , Male , Middle Aged , Retrospective Studies
6.
Toxicon ; 50(5): 627-38, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17640694

ABSTRACT

Several natural isomers of the seizurogenic neurotoxin domoic acid (DA) have been found to occur at up to mg/kg levels in shellfish. The aim of the current study was to assess the neurotoxic potency of isodomoic acids A and C (Iso-A and Iso-C), recently isolated from commercial shellfish. Hippocampal slices were obtained from young adult rats and maintained in a tissue recording chamber. Synaptically evoked population spikes were recorded in region CA1 before and after exposure to DA or its isomers. Both Iso-A and Iso-C produced transient neuronal hyperexcitability followed by a dose-dependent suppression of population spikes, but were, respectively, 4- and 20-fold less potent than DA (spike area: EC50 DA=237 nM; Iso-A=939 nM; Iso-C=4.6 microM). In the hippocampus, DA preconditioning induces tolerance to subsequent DA toxicity. However, in the present study neither Iso-A nor Iso-C were effective as preconditioning agents. Competitive binding studies using homomeric GluR6 kainate (kainic acid, KA) receptors showed the affinity of Iso-A to be 40-fold lower than DA (Ki DA=3.35 nM; Iso-A=130 nM). Together with earlier work showing Iso-C affinity at GluR6 receptors to be 240-fold lower than DA, our results suggest that neuroexcitatory effects of Iso-A in CA1 may involve both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and KA receptors, while Iso-C likely involves the activation of AMPA receptors alone.


Subject(s)
Excitatory Postsynaptic Potentials/drug effects , Heptanoic Acids/pharmacology , Hippocampus/drug effects , Marine Toxins/pharmacology , Neurotoxins/pharmacology , Receptors, Kainic Acid/metabolism , Animals , Binding, Competitive , Dose-Response Relationship, Drug , Drug Tolerance , Excitatory Postsynaptic Potentials/physiology , Hippocampus/metabolism , Isomerism , Kainic Acid/analogs & derivatives , Kainic Acid/pharmacology , Male , Organ Culture Techniques , Rats , Rats, Wistar
7.
Transplant Proc ; 38(7): 2080-3, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16980005

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common posttransplantation malignancy in hepatitis B virus (HBV) endemic areas. The aim of this study was to review the significant effect of liver cirrhosis on the outcome of renal allograft recipients with chronic hepatitis B. We performed a retrograde analysis of the clinical presentations of 66 hepatitis B surface antigen-positive kidney allograft recipients during the past 25 years with a mean follow-up of 76 months. Seven patients were diagnosed with HCC. The patients were subgrouped into cirrhotic versus noncirrhotic liver cohorts. Among renal allograft recipients with HBV infection, patients with cirrhotic livers had a higher risk of HCC (P = .003) and mortality (P = .025) than those with a noncirrhotic liver. The outcome was poor among the cirrhotic liver group. Pretransplantation liver biopsy may be indicated for the recipient candidate with HBV infection. Liver cirrhosis may be an exclusion criterion for the renal transplant waiting list due to the high incidence of HCC and the poor patient survival.


Subject(s)
Carcinoma, Hepatocellular/epidemiology , Kidney Transplantation/adverse effects , Liver Neoplasms/epidemiology , Adult , Carcinoma, Hepatocellular/mortality , Female , Follow-Up Studies , Hepatitis C/epidemiology , Hepatitis C/mortality , Humans , Liver Cirrhosis/epidemiology , Liver Cirrhosis/mortality , Liver Diseases/epidemiology , Liver Diseases/mortality , Liver Neoplasms/mortality , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/mortality , Retrospective Studies , Survival Analysis , Time Factors
8.
Transplant Proc ; 36(8): 2438-9, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15561272

ABSTRACT

Dysfunction of the renal graft may not only be due to rejection but also other causes such as ischemia and reperfusion injury and calcineurin inhibitor nephrotoxicity. Antioxidant free radical scavengers may decrease oxidative stress and lipid peroxidation. Previous animal studies suggest that vitamins C (ascorbic acid) and E (alpha-tocopherol) are both strong antioxidants, that decrease oxidative stress caused by ischemia-reperfusion injury and calcineurin inhibitor nephrotoxicity. But there have been only limited reports about clinical efficacy. We report five cases supplemented with vitamin C (500 mg per day), vitamin E (500 mg per day), or both. After a 1- to 3-month prescription, the serum creatinine level decreased more than 20% from the original value. Interestingly, one patient had this experience: he ceased vitamin E for 1 month due to noncompliance. The serum creatinine level increased more than 50%. When he took vitamin E again, his serum creatinine level declined and returned to the previous level. From our limited experience, antioxidant supplementation with vitamin C or E may improve renal transplant function, especially in grafts donated from marginal donors.


Subject(s)
Antioxidants/therapeutic use , Ascorbic Acid/therapeutic use , Dietary Supplements , Kidney Transplantation/physiology , Vitamin E/therapeutic use , Adult , Antioxidants/administration & dosage , Creatinine/blood , Female , Follow-Up Studies , Humans , Male , Time Factors
9.
Eur J Surg Oncol ; 30(4): 414-20, 2004 May.
Article in English | MEDLINE | ID: mdl-15063895

ABSTRACT

AIM: The prognosis of patients with recurrent hepatocellular carcinoma (HCC) after hepatic resection varies widely. This study analyzed long-term survival and prognostic factors of patients with recurrent HCC after hepatectomy. METHODS: From July 1991 to December 2000, 623 patients underwent hepatic resection for HCC. Of those, 347 (56.5%) patients had tumour recurrence, and 286 patients with follow-up time more than 24 months after recurrence were enrolled. Twenty-seven clinicopathologic factors underwent both univariate and multivariate analysis. RESULTS: Of these 286 patients, survival times after tumour recurrence were mean 672+/-619 days; median 468 days; and, range 10-3753 days. The overall 1-, 3-, 5-, and 10-year post-recurrence survival rates were 61.5, 33.4, 18.2, and 9.0%, respectively. Seventy (24.5%) patients were alive at the time of study, and 10 of the 34 patients who underwent re-resection were disease-free. By Cox regression analysis, multiple initial tumours (relative risk (RR) 1.428), recurrent multiple (RR 1.372), extrahepatic recurrence (RR 2.434), recurrent tumour size >2 cm (RR 1.926), post-hepatectomy period until recurrence <1 year (RR 1.769), and non-resectional treatment of recurrent tumours (RR 3.527) were independent prognostic factors for post-recurrent survival rates. CONCLUSIONS: In patients with recurrent HCC after hepatectomy, both initial and recurrent tumour factors influenced their prognosis. Early detection of recurrent tumours is important. Re-resection correlated with better post-recurrent survival rates.


Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/mortality , Aged , Aneuploidy , Carcinoma, Hepatocellular/mortality , Disease-Free Survival , Follow-Up Studies , Hepatectomy , Humans , Liver Neoplasms/mortality , Middle Aged , Prognosis , Survival Analysis , Treatment Outcome
10.
J Formos Med Assoc ; 100(7): 443-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11579608

ABSTRACT

BACKGROUND AND PURPOSE: Hepatitis B and C viral infections are important factors in the development of hepatocellular carcinoma (HCC). This study examined the clinicopathologic and prognostic differences in patients with hepatitis B- and C-related resectable HCC. METHODS: A total of 270 HCC patients who underwent hepatic resection were enrolled. Among these patients, 211 were positive for hepatitis B surface antigen (HBsAg) and 59 were positive for anti-hepatitis C virus antibody (anti-HCV). The clinical manifestations, pathologic features, and treatment outcomes were compared between the HBsAg-positive and anti-HCV-positive groups. RESULTS: Compared to anti-HCV-positive patients, HBsAg-positive patients were significantly younger, had a higher familial incidence of HCC, larger tumor size, and a higher incidence of multiple tumors. HCC patients who were anti-HCV positive had worse liver function and a higher incidence of history of blood transfusion. DNA flow cytometric analysis revealed significantly more proliferative activity in the non-tumor part of the liver in HBsAg-positive HCC patients. The 1-, 3-, and 5-year overall survival rates of HBsAg-positive patients were 79%, 57%, and 48%, respectively, and for anti-HCV-positive patients were 91%, 75%, and 62%, respectively. HBsAg-positive patients had a significantly lower overall survival rate than anti-HCV-positive patients (p = 0.018). CONCLUSIONS: HBsAg-positive patients with resectable HCC had a less favorable survival rate after tumor resection than anti-HCV-positive HCC patients. This survival difference might have been related to the relatively advanced stage of disease and the higher proliferative activity of the non-tumor part of the liver in HBsAg-positive HCC patients.


Subject(s)
Carcinoma, Hepatocellular/virology , Hepatitis B Surface Antigens/blood , Hepatitis C Antibodies/blood , Liver Neoplasms/virology , Adult , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Female , Hepatectomy , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Prognosis , Survival Rate
11.
Dig Dis Sci ; 46(3): 469-75, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11318517

ABSTRACT

The impact of hepatitis B virus (HBV) infection on the long-term outcome of kidney transplant patients is controversial. A total of 34 chronic hepatitis B surface antigen (HBsAg) carriers among 143 renal allograft recipients were identified in this study (mean follow-up period: 5.6+/-3.3 years; range: 1-13 years). During the follow-up, one HBsAg-positive recipient with preexisting cirrhosis died of liver failure, and seven (21%) others developed serious HBV-related complications (four fulminant hepatitis, two hepatocellular carcinoma, one cirrhosis), and four died. Although HBsAg-positive recipients had a higher rate of liver-related complications and deaths than HBsAg-negative recipients did, there were no significant differences in the long-term graft and patient survival between the two groups. The survival rates, liver-related complications, and deaths in HBsAg-positive allograft recipients and 28 HBsAg-positive uremic patients under dialysis were similar. In conclusion, HBV infection is not a contraindication to kidney transplantation. However, pretransplant candidates should be warned of potentially serious liver-related complications.


Subject(s)
Hepatitis B, Chronic/complications , Kidney Transplantation/mortality , Adolescent , Adult , Aged , Child , Female , Follow-Up Studies , Hepatitis B Surface Antigens/blood , Humans , Male , Middle Aged , Postoperative Complications , Prognosis , Survival Rate , Transplantation, Homologous , Treatment Outcome
12.
Hepatogastroenterology ; 48(37): 169-73, 2001.
Article in English | MEDLINE | ID: mdl-11268958

ABSTRACT

BACKGROUND/AIMS: The impact of HCV (hepatitis C virus) infection on the long-term outcome of kidney transplant patients is controversial. METHODOLOGY: Eighty-four renal allograft recipients who were seronegative for hepatitis B surface antigen and had been screened for antibody to hepatitis C virus (anti-HCV) were included. The outcome and survival were compared between anti-HCV-positive (n = 30, group 1) and anti-HCV-negative (n = 54, group 2) kidney transplant patients. Group 1 patients were further compared to 52 anti-HCV-positive end-stage renal disease patients (group 3) who were on chronic dialysis. RESULTS: Group 1 patients had a higher prevalence of chronic hepatitis than group 2 and group 3 patients did (67% vs. 2% and 31%). Liver-related complications and deaths between group 1 and group 2, and group 1 and group 3 patients were not significantly different. The comparisons of the long-term survival between these groups showed no significant differences, despite group 3 patients had a higher overall mortality rate. Cox regression analysis confirmed that age more than 45 years was the only independent factor that affected survival in anti-HCV-positive end-stage renal disease patients with or without kidney transplantation. CONCLUSIONS: HCV infection is not a contraindication to kidney transplantation. For anti-HCV-positive end stage renal disease patients, survival is better in younger patients, and is not influenced by kidney transplantation or continuing dialysis.


Subject(s)
Hepatitis C, Chronic/complications , Kidney Failure, Chronic/complications , Kidney Transplantation , Adolescent , Adult , Aged , Child , Female , Graft Rejection , Hepatitis C Antibodies/analysis , Humans , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Failure, Chronic/therapy , Kidney Transplantation/mortality , Male , Middle Aged , Renal Dialysis , Survival Analysis , Survival Rate , Treatment Outcome
13.
S Afr J Surg ; 39(2): 46-8; discussion 48-9, 2001 May.
Article in English | MEDLINE | ID: mdl-14601448

ABSTRACT

This is a clinical study of the use of several monitoring techniques to evaluate the effect of total hepatic inflow occlusion on intestinal ischaemia during liver resection. A total of 8 patients was studied. Parameters measured included intestinal oxygen extraction ratio, portal venous and arterial lactate levels and intestinal intramucosal pH (pHi), measured by an intraluminal tonometer. When venous outflow of the intestine was occluded, intestinal oxygen extraction ratio increased and portal venous lactate increased significantly, but arterial lactate did not increase significantly until after 60 minutes of occlusion. Intestinal pHi decreased significantly after 60 minutes. Following release of the occlusion, oxygen extraction and pHi returned to normal in 7 out of 8 patients. The 1 patient who had a persistent decrease in pHi died postoperatively. These findings indicate that a marked drop in pHi after total portal occlusion and persistent low pHi following the release of a portal occlusion are associated with the development of complications and mortality during liver resection.


Subject(s)
Intestines/blood supply , Adult , Aged , Female , Gallstones/surgery , Hepatectomy , Humans , Lactic Acid/blood , Liver Neoplasms/surgery , Male , Middle Aged , Portal Vein , Postoperative Period , Regional Blood Flow
15.
Metab Brain Dis ; 15(1): 65-81, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10885541

ABSTRACT

We have characterized a region of the mouse vesicular acetylcholine transporter(VAChT)/choline acetyltransferase (ChAT) gene locus that serves as a cholinergic-specific promoter for the expression of both VAChT and ChAT genes, as well as a reporter gene (LacZ) in vivo. We have used this promoter to direct the expression of an inhibitor peptide, derived from the calcineurin (CalN) autoregulatory domain, to directly neutralize the function of CalN to define the role of this Ca2+/Calmodulin regulated phosphatase in neurite outgrowth. Targeted inhibition of CalN promotes neurite outgrowth in PC12 cells in the presence of NGF, as early as 24 h after transfection. Inhibition of CalN-mediated enhancement of neurite outgrowth in PC12 cells reaches a maximum effect within the first 4 to 6 days after transfection, and does not cause adverse effects when highly expressed for up to 12 days. Cyclosporin A, a nontargeted CalN inhibitor, increases the number of neurites in mock transfected cells by 1.5 fold, while in transfected PC12 cells, the expression of the CalN inhibitor peptide increases the neurite number by 1.8 fold. These data demonstrate that CalN is an important regulator of the neurotrophic response in cholinergic cells and may prove valuable in developing treatment strategies to promote recovery from neurological injury.


Subject(s)
Calcineurin/genetics , Carrier Proteins/genetics , Choline O-Acetyltransferase/genetics , Gene Targeting , Membrane Transport Proteins , Nerve Growth Factor/pharmacology , Neurites/drug effects , Neurites/physiology , PC12 Cells/physiology , Promoter Regions, Genetic/physiology , Vesicular Transport Proteins , Animals , Calcineurin/chemistry , Neurons/physiology , Peptide Fragments/pharmacology , Rats , Vesicular Acetylcholine Transport Proteins
16.
Cancer ; 88(11): 2464-70, 2000 Jun 01.
Article in English | MEDLINE | ID: mdl-10861421

ABSTRACT

BACKGROUND: The expression of heat shock protein-27 (HSP-27) has been detected in some human tumors. In this study the authors investigated HSP-27 expression in patients with hepatocellular carcinoma (HCC) and examined its prognostic significance. METHODS: Expression of HSP-27 was studied in 58 HCC and adjacent noncancerous liver tissues by immunohistochemical stain. The relation between its expression and eight known prognostic factors was evaluated. RESULTS: Of the 58 HCC tissues studied, the presence of HSP-27 was demonstrated in 45 tissues (77.6%); low expression ( 25%) was demonstrated in 28 tissues. A significantly higher distribution of HSP-27 expression in HCC tissues compared with adjacent noncancerous liver tissues was obtained (P < 0.0001). Patients with high HSP-27 expression had a significantly higher histologic tumor grade than those with low HSP-27 expression (P = 0.001). The 5-year disease free survival rate of patients with high HSP-27 expression was 21.4% versus 59.3% for patients with low HSP-27 expression (P < 0.001). A similar relation was observed with overall survival (33.3% vs. 64. 8%; P = 0.009). HSP-27 expression was also identified to be a significant and powerful prognostic indicator for disease free survival (odds ratio = 2.25; P = 0.034) and for overall survival (odds ratio = 2.72; P = 0.015). CONCLUSIONS: The current study data suggest that HSP-27 expression is a powerful prognostic indicator and is related to histologic grade and survival of patients with HCC.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Heat-Shock Proteins/metabolism , Liver Neoplasms/metabolism , Neoplasm Proteins/metabolism , Adult , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Chi-Square Distribution , Female , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Prognosis , Statistics, Nonparametric , Survival Rate
17.
Surgery ; 127(6): 603-8, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10840353

ABSTRACT

BACKGROUND: Tumor venous invasion in patients with resectable hepatocellular carcinoma (HCC) is frequent and can be macroscopic and microscopic or microscopic alone. Although macroscopic invasion is a well-established prognostic indicator, the clinical significance of microscopic invasion remains unclear. METHODS: There were 322 patients enrolled who had undergone curative resection for HCC. The clinicopathologic factors and prognostic significance associated with macroscopic and microscopic venous invasion were analyzed. RESULTS: Macroscopic invasion was observed in 50 patients (15.5%) and microscopic invasion in 190 (59.0%). The larger the tumor, the more the incidence of venous invasion. There were 140 patients with microscopic invasion only (Group 1). Patients with macroscopic invasion (Group 2, n = 50) also had microscopic invasion. Compared with patients without venous invasion (Group 3, n = 132), Group 1 had a higher alpha-fetoprotein level, a larger tumor size, and more tumors without encapsulation. For group 1, the 1-, 3-, and 5-year disease-free survival rates were 65.6%, 41.6%, and 30.8%, respectively. The 1-, 3-, and 5-year overall survival rates were 87. 8%, 60.0%, and 52.7%, respectively. The survival rates of group 1 were lower than those of group 3 and higher than those of group 2 (P <.05). Multivariate analysis indicated that microscopic and macroscopic venous invasion, surgical margin, indocyanine-green retention, and tumor size and number were significant predictors of postresectional survival. CONCLUSIONS: In HCC patients, microscopic venous invasion is frequent and related independently to postresectional outcome.


Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/secondary , Liver Neoplasms/pathology , Aged , Female , Hepatic Veins/pathology , Humans , Male , Middle Aged , Neoplasm Invasiveness , Portal Vein/pathology
18.
N Engl J Med ; 342(26): 1946-52, 2000 Jun 29.
Article in English | MEDLINE | ID: mdl-10874062

ABSTRACT

BACKGROUND: Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2. METHODS: We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line. RESULTS: At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups. CONCLUSIONS: In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.


Subject(s)
Adenomatous Polyposis Coli/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cyclooxygenase Inhibitors/therapeutic use , Isoenzymes/antagonists & inhibitors , Isoenzymes/pharmacology , Prostaglandin-Endoperoxide Synthases/pharmacology , Sulfonamides/therapeutic use , Adult , Celecoxib , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Membrane Proteins , Pyrazoles , Sulfonamides/adverse effects
19.
Jpn J Clin Oncol ; 30(3): 122-5, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10798538

ABSTRACT

BACKGROUND: Acute disseminated intravascular coagulation (DIC) is a rare but severe complication of gastric adenocarcinoma. Conventional treatments, such as fresh frozen plasma, platelet replacement and heparin injections, are disappointing. The only way to correct this fatal condition is to control the underlying cancer promptly by effective chemotherapy. Here the successful initial control of acute DIC in gastric cancer patients with weekly EEPFL chemotherapy is reported. METHODS: Advanced gastric cancer patients complicated with acute DIC were eligible. Patients were treated with weekly EEPFL therapy (etoposide 40, epirubicin 10, cisplatin 25, 5-fluorouracil 2200 and leucovorin 120 mg/m2 ). Response, survival and toxicity were evaluated. RESULTS: From April 1997 to April 1999, six patients were included in this study. All patients received EEPFL chemotherapy. Clinical and laboratory evidence of acute DIC stabilized quickly after starting chemotherapy. Four patients showed a partial response, one stable disease and one progressive disease. The toxicity was mild and well tolerated. Median survival was 28 weeks (12, 14, 26, 30, 30 and 32 weeks). All patients suffered from a relapse of DIC after initial successful control and died within 30 days of clinical and laboratory evidence of acute DIC relapse. CONCLUSION: EEPFL therapy is an effective chemotherapy regimen for patients with advanced gastric cancer associated with acute DIC. The prognosis is poor if the DIC relapses after the initial successful control.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disseminated Intravascular Coagulation/complications , Stomach Neoplasms/drug therapy , Acute Disease , Adenocarcinoma/complications , Adenocarcinoma/mortality , Adult , Aged , Cisplatin/administration & dosage , Cisplatin/adverse effects , Epirubicin/administration & dosage , Epirubicin/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Stomach Neoplasms/complications , Stomach Neoplasms/mortality , Survival Rate
20.
Hepatogastroenterology ; 47(32): 446-9, 2000.
Article in English | MEDLINE | ID: mdl-10791210

ABSTRACT

BACKGROUND/AIMS: Hepatocellular carcinoma is notably more prevalent in male. The purpose of this study was to assess the surgical results in male and female cirrhotic patients. METHODOLOGY: The surgical outcomes of 129 hepatocellular carcinoma patients with cirrhosis, including 109 males and 20 females, who had undergone hepatic resection were studied. The clinical, histologic features, DNA ploidy and proliferative phase fraction of tumor and cirrhotic liver were compared between male and female patients. RESULTS: Female patients had significantly lower incidences of history of smoking (5.6% vs. 52.9%, P < 0.001), alcohol intake (5.6% vs. 42.3%, P = 0.003) and hepatitis B surface antigen positivity (47.1% vs. 73.5%, P = 0.028) than male. Cell-cycle analysis of tumor part revealed female had a significant lower G2M phase fraction (3.4%) than male (5.7%) (P = 0.027). The 1-, 3-, and 5-year disease-free survival rates in male and female patients were 65.5% and 88.2%, 36% and 64.4%, and 29.7% and 64.4%, respectively. Female patients had a significantly better disease-free survival than male (P = 0.034, log-rank test). CONCLUSIONS: Female hepatocellular carcinoma with cirrhosis had lower incidences of hepatitis B surface antigenemia, alcohol abuse and lower DNA postsynthetic phase fraction in tumor tissue than male. Consequently, female hepatocellular carcinoma with cirrhosis had better survival than male.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/surgery , Postoperative Complications/mortality , Aged , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/mortality , Female , Humans , Liver Neoplasms/etiology , Liver Neoplasms/mortality , Male , Middle Aged , Risk Factors , Sex Factors , Survival Rate
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