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J W Marsh

Publications and source records attributed to J W Marsh.

At least 37 records · Page 2Linked to original sources
PubMed1999

Should hepatomas be treated with hepatic resection or transplantation?

BACKGROUND: The aim of this collaborative study was to compare the long term results of hepatic resection (Hx) with those of orthotopic liver transplantation (OLTx) in large numbers of cirrhotic patients with hepatocellular carcinoma (HCC) and to delineate the roles of these two surgical treatments. METHODS: The databases of the National Cancer Center Hospital in Japan and the University of Pittsburgh Medical Center in the U. S. were exchanged and 294 cirrhotic patients who underwent curative Hx and 270 cirrhotic patients who underwent curative OLTx were selected for comparison. RESULTS: The mortality rate within 30 days and that within 150 days after Hx were significantly lower than those after OLTx (P = 0.001 and P = 0.00007, respectively). Overall survival was similar between the Hx group and the OLTx group (P = 0.40). When compared in the HCC patients without macroscopic vascular invasion and lymph node metastases, the overall survival rate after OLTx was significantly higher than that after Hx (P = 0.006). However, this difference was not significant between the patients with Child-Pugh Grade A tumors in the Hx group and all patients (majority with Child-Pugh Grade C tumors) in the OLTx group (P = 0.25). Tumor free survival after OLTx was significantly higher than that after Hx (P < 0.0001), particularly in HCCs measuring </=5 cm, unilobarly distributed tumors, and HCCs with either no or only microscopic vascular invasion. In HCCs measuring > 5 cm and those with macroscopic vascular invasion, the tumor free survival rate was similar between the Hx group and the OLTx group. CONCLUSIONS: In the face of organ shortage, HCC developing in a well compensated cirrhotic liver initially may be treated with Hx. However, the authors believe OLTx should be applied selectively to those patients with tumor recurrence and/or progressive hepatic failure.

Carcinoma, Hepatocellular↗
PubMed1999

HIV-1 Nef increases T cell activation in a stimulus-dependent manner.

Lentiviral Nef increases viral replication in vivo, plays a direct role in pathogenesis, and increases viral particle infectivity. We now find that HIV Nef also increases the activation of T cells, a cellular state required for optimal viral replication. This enhancement is stimulant-dependent. As defined by IL-2 generation, activation of T cells stimulated with classical mitogens [phorbol 12-myristate 13-acetate (PMA) + anti-CD3, PMA + phytohemagglutinin, and PMA + ionomycin] is unaffected by the expression of Nef. However, Nef increases IL-2 secretion when cells are stimulated through the T cell receptor and the costimulus receptor (CD28). This increase in activation, which depends on Nef myristylation, is caused by an increase in the number of cells reaching full activation and not by an increase in the amount of IL-2 secreted per cell. These findings demonstrate that Nef lowers the threshold of the dual-receptor T cell activation pathway. The capacity of Nef to increase T cell activity may be very important in vivo when Nef is the predominant or the only viral gene product expressed.

Antibodies, Monoclonal↗
PubMed1999

A prospective, randomized trial of tacrolimus/prednisone versus tacrolimus/prednisone/mycophenolate mofetil in renal transplant recipients.

BACKGROUND: Between September 20, 1995 and September 20, 1997, 208 adult patients undergoing renal transplantation were randomized to receive tacrolimus/prednisone (n=106) or tacrolimus/prednisone/mycophenolate mofetil (n=102), with the goal of reducing the incidence of rejection. METHODS: The mean recipient age was 50.7+/-13.7 years. Sixty-three (30.3%) patients were 60 years of age or older at the time of transplantation. The mean donor age was 34.5+/-21.7 years. The mean cold ischemia time was 30.5+/-9.2 hr. The mean follow-up is 15+/-7 months. RESULTS: The overall 1-year actuarial patient survival was 94%; the overall 1-year actuarial graft survival was 87%. When the patient and graft survival data were stratified to recipients under the age of 60 who did not have delayed graft function, the overall 1-year actuarial patient survival was 97%, and the corresponding 1-year actuarial graft survival was 93%. There were no differences between the two groups. The overall incidence of rejection was 36%; in the double-therapy group, it was 44%, whereas in the triple therapy group, it was 27% (P=0.014). The mean serum creatinine was 1.6+/-0.8 mg/dl. A total of 36% of the successfully transplanted patients were taken off prednisone; 32% of the patients were taken off antihypertensive medications. The incidence of delayed graft function was 21%, the incidence of cytomegalovirus was 12.5%, and the initial and final incidences of posttransplant insulin-dependent diabetes mellitus were 7.0% and 2.9%; again, there was no difference between the two groups. CONCLUSIONS: This trial suggests that the combination of tacrolimus, steroids, and mycophenolate mofetil is associated with excellent patient and graft survival and a lower incidence of rejection than the combination of tacrolimus and steroids.

Adolescent↗
PubMed1999

Hepatobiliary malignancies. Primary hepatic malignant neoplasms.

Primary hepatic tumors are epithelial, mesenchymal, or mixed in origin. Of these, epithelial tumors are the most common and include hepatocellular carcinoma, cholangiocarcinoma, mixed hepatocholangiocarcinoma, hepatoblastoma, and a variety of more rare tumors. Hepatocellular carcinoma, also know as hepatoma or malignant hepatoma, is the most common, followed by cholangiocarcinoma. This article discusses these two malignancies.

Carcinoma, Hepatocellular↗
PubMed1999

Hepatic resection for metastatic colorectal adenocarcinoma: a proposal of a prognostic scoring system.

BACKGROUND: Hepatic resection for metastatic colorectal cancer provides excellent longterm results in a substantial proportion of patients. Although various prognostic risk factors have been identified, there has been no dependable staging or prognostic scoring system for metastatic hepatic tumors. STUDY DESIGN: Various clinical and pathologic risk factors were examined in 305 consecutive patients who underwent primary hepatic resections for metastatic colorectal cancer. Survival rates were estimated by the Cox proportional hazards model using the equation: S(t) = [So(t)]exp(R-Ro), where So(t) is the survival rate of patients with none of the identified risk factors and Ro = 0. RESULTS: Preliminary multivariate analysis revealed that independently significant negative prognosticators were: (1) positive surgical margins, (2) extrahepatic tumor involvement including the lymph node(s), (3) tumor number of three or more, (4) bilobar tumors, and (5) time from treatment of the primary tumor to hepatic recurrence of 30 months or less. Because the survival rates of the 62 patients with positive margins or extrahepatic tumor were uniformly very poor, multivariate analysis was repeated in the remaining 243 patients who did not have these lethal risk factors. The reanalysis revealed that independently significant poor prognosticators were: (1) tumor number of three or more, (2) tumor size greater than 8 cm, (3) time to hepatic recurrence of 30 months or less, and (4) bilobar tumors. Risk scores (R) for tumor recurrence of the culled cohort (n = 243) were calculated by summation of coefficients from the multivariate analysis and were divided into five groups: grade 1, no risk factors (R = 0); grade 2, one risk factor (R = 0.3 to 0.7); grade 3, two risk factors (R = 0.7 to 1.1); grade 4, three risk factors (R= 1.2 to 1.6); and grade 5, four risk factors (R > 1.6). Grade 6 consisted of the 62 culled patients with positive margins or extrahepatic tumor. Kaplan-Meier and Cox proportional hazards estimated 5-year survival rates of grade 1 to 6 patients were 48.3% and 48.3%, 36.6% and 33.7%, 19.9% and 17.9%, 11.9% and 6.4%, 0% and 1.1%, and 0% and 0%, respectively (p < 0.0001). CONCLUSIONS: The proposed risk-score grading predicted the survival differences extremely well. Estimated survival as determined by the Cox proportional hazards model was similar to that determined by the Kaplan-Meier method. Verification and further improvements of the proposed system are awaited by other centers or international collaborative studies.

Adenocarcinoma↗
PubMed1999

Screening for cerebral aneurysm in patients with polycystic liver disease.

BACKGROUND: Polycystic liver disease (PCLD) is an autosomal dominant disease characterized by multiple macrocystic lesions throughout the liver. The association between PCLD and cerebral aneurysm is well documented, and approximately 20% of patients with PCLD have demonstrable cerebral aneurysms at autopsy. The prevalence reported from autopsy series, however, may not reflect the true prevalence in patients with PCLD. We undertook this study to evaluate the prevalence and diagnosis of cerebral aneurysms in screening cerebral studies in patients with PCLD. METHODS: Patients were identified by searching the hepatobiliary surgical service data base and hospital medical records. Hospital charts were reviewed to confirm presence of PCLD and to identify screening studies for cerebral aneurysms. RESULTS: Ten patients with PCLD received screening studies of the cerebral vasculature during a 10 1/2-year period. One patient was found to have an asymptomatic cerebral aneurysm. A 45-year-old woman with no other significant medical history was referred for evaluation of PCLD. Screening magnetic resonance angiography (MRA) revealed a 5 mm aneurysm extending anteriorly near the origin of the right ophthalmic artery, without evidence of rupture. Cerebral angiography confirmed these findings, and the aneurysm was clipped. CONCLUSIONS: Because cerebral aneurysms can be an important source of morbidity and mortality in PCLD, we recommend screening by MRA or by computed tomographic angiography (CTA) of the cerebral vasculature in all patients who have PCLD.

Adult↗
PubMed1999

Genetic and transcriptional analyses of the Vibrio cholerae mannose-sensitive hemagglutinin type 4 pilus gene locus.

The mannose-sensitive hemagglutinin (MSHA) of the Vibrio cholerae O1 El Tor biotype is a member of the family of type 4 pili. Type 4 pili are found on the surface of a variety of gram-negative bacteria and have demonstrated importance as host colonization factors, bacteriophage receptors, and mediators of DNA transfer. The gene locus required for the assembly and secretion of the MSHA pilus has been localized to a 16.7-kb region of the V. cholerae chromosome. Sixteen genes required for hemagglutination, including five that encode prepilin or prepilin-like proteins, have been identified. Examination of MSHA-specific cDNAs has localized two promoters that drive expression of these genes. This evidence indicates that the MSHA gene locus is transcriptionally organized into two operons, one encoding the secretory components and the other encoding the structural subunits, an arrangement unique among previously characterized type 4 pilus loci. The genes flanking the MSHA locus encode proteins that show homology to YhdA and MreB of Escherichia coli. In E. coli, the yhdA and mreB genes are adjacent to each other on the chromosome. The finding that the MSHA locus lies between these two E. coli homologs and that it is flanked by a 7-bp direct repeat suggests that the MSHA locus may have been acquired as a mobile genetic element.

Bacterial Proteins↗
PubMed1999

Surgical experience with hepatic colorectal metastasis.

The outcome of 134 patients undergoing hepatic resection for colorectal metastasis was studied. Current follow-up was available in 98 per cent of patients, for more than 5 years in 58 patients, and totaling 360 patient-years. Patients (52% male) had an average age of 62 +/- 1 years (standard error of the mean). Time lapse between the primary colon surgery and hepatic resection was a median of 16 months and a mean of 19 +/- 1 months. Thirty-two (24%) were operated on within 6 months for both their primary tumor and hepatic metastasis. Intensive care unit and total hospital length of stay were a median of 1 and 7 days, respectively. Pathology reports demonstrated that on average there were 2.0 +/- 0.1 lesions, with the largest lesion measuring 4.4 +/- 0.2 cm. In 72 per cent of patients, the lesions were found in one lobe only. CEA was elevated in 83 per cent of patients preoperatively and was 60 +/- 11 ng/mL before and 4.0 +/- 0.5 ng/mL after hepatic resection. Patient survival was 81 per cent at 1 year, 50 per cent at 3 years, 36 per cent at 5 years, and 23 per cent at 10 years. Actual 5- and 10-year survival was 22 of 58 (38%) patients and 4 of 21 (19%) patients respectively. Disease-free survival was 58 per cent at 1 year, 27 per cent at 3 years, 16 per cent at 5 years, and 12 per cent at 7 years. Survival was much better for one to four lesions than for five or more lesions (P < 0.01). Several other potential risk factors did not affect survival, including whether the patient received chemotherapy after hepatic resection. There were 36 (43%) patients who recurred with hepatic involvement only, 27 (32%) including hepatic involvement and 21 (25%) with nonhepatic involvement only. There were 15 patients who went on to receive repeat hepatic resections, with a 5-year survival of 74 per cent and disease-free survival of 58 per cent. Hepatic resection provides the best outcome of any form of therapy for selected patients with isolated hepatic metastasis.

Colectomy↗
PubMed1998

Undetected hepatocellular carcinoma: clinical features and outcome after liver transplantation.

The aim of the study was to define the clinical characteristics and outcome of patients found to have an undetected hepatocellular carcinoma (HCC) at liver transplantation. Patients who underwent liver transplantation and were found to have a hepatoma with a prior workup showing normal alpha-fetoprotein levels and no corresponding lesion on radiological evaluation were defined as having an undetected HCC. Detailed information was collected, and the last abdominal computed tomographic (CT) scan before transplantation was performed was retrospectively reviewed. Thirty-nine patients had a tumor that met the criteria for an undetected hepatoma. The most common causes for pretransplantation liver disease were hepatitis C virus (HCV) (49%) and alcohol use (28%). Tumor size was 2 cm or less in 85% of the patients, vascular invasion was detected in 31% of the patients, and tumor, node, metastasis (TNM) classification was stage I or II in 77% of the patients. Review of the last CT scan before transplantation showed that the lesion was evident in retrospect in only 15% of the patients. Thirty-two patients (82%) remained alive at the time of the study with a mean follow-up of 30 months. Metastatic HCC was detected in 1 patient 7 months after transplantation. There were no other tumor recurrences. Survival analysis showed no significant differences when tumor size, stage, presence of vascular invasion, or causes of pretransplantation liver disease were compared. Undetected HCCs represent a significant percentage of total hepatomas in patients undergoing liver transplantation. Most patients have small, early-stage tumors, but tumors greater than 2 cm or of advanced stage are also frequently found in this population. Overall and tumor-free survival appear to be favorable.

Adult↗
PubMed1998

Liver transplantation in the treatment of hepatocellular carcinoma.

We aimed to determine the most appropriate candidates for liver transplantation based on their survival outcomes. Two hundred and fourteen patients who were transplanted in the presence of hepatocellular carcinoma (HCC) were analyzed. Patient groups were selected as "good risk" candidates for transplantation by our previously developed artificial network model or by the classic pTNM pathological classification system. The survival of the model-selected candidate groups was then compared to the survival of the candidates chosen as "good risk" by the pTNM classification (i.e. , pTNM stages I + II and pTNM stages I + II + III). Suitability for transplantation was judged by long-term survival rates (i.e., 1-10 years post-transplant). By using the neural network prediction model and the subsequent subgroup case analysis, it was possible to generate those combinations of risk factors which predetermined patient survival through HCC recurrence. By applying the developed neural network model to the transplant candidate pool for patients with HCC, it was possible to select the maximum number of suitable candidates for transplantation while minimizing donor organ loss to recurrent HCC.

Adolescent↗
PubMed1998

Treatment of hilar cholangiocarcinoma (Klatskin tumors) with hepatic resection or transplantation.

BACKGROUND: Because of the rarity of hilar cholangiocarcinoma, its prognostic risk factors have not been sufficiently analyzed. This retrospective study was undertaken to evaluate various pathologic risk factors which influenced survival after curative hepatic resection or transplantation. METHODS: Between 1981 and 1996, 72 patients (43 males and 29 females) with hilar cholangiocarcinoma underwent hepatic resection (34 patients) or transplantation (38 patients) with curative intent. Medical records and pathologic specimens were reviewed to examine the various prognostic risk factors. Survival was calculated by the method of Kaplan-Meier using the log rank test with adjustment for the type of operation. Survival statistics were calculated first for each kind of treatment separately, and then combined for the calculation of the final significance value. RESULTS: Survival rates for 1, 3, and 5 years after hepatic resection were 74%, 34%, and 9%, respectively, and those after transplantation were 60%, 32%, and 25%, respectively. Univariate analysis revealed that T-3, positive lymph nodes, positive surgical margins, and pTNM stage III and IV were statistically significant poor prognostic factors. Multivariate analysis revealed that pTNM stage 0, I, and II, negative lymph node, and negative surgical margins were statistically significant good prognostic factors. For the patients in pTNM stage 0-II with negative surgical margins, 1-, 3-, and 5-year survivals were 80%, 73%, and 73%, respectively. For patients in pTNM stage IV-A with negative lymph nodes and surgical margins, 1-, 3-, and 5-year survivals were 66%, 37%, and 37%, respectively. CONCLUSIONS: Satisfactory longterm survivals can be obtained by curative surgery for hilar cholangiocarcinoma either with hepatic resection or liver transplantation. Redefining pTNM stage III and IV-A is proposed to better define prognosis.

Adult↗
PubMed1998

Identification of the Vibrio cholerae type 4 prepilin peptidase required for cholera toxin secretion and pilus formation.

Cholera toxin secretion is dependent upon the extracellular protein secretion apparatus encoded by the eps gene locus of Vibrio cholerae. Although the eps gene locus encodes several type four prepilin-like proteins, the peptidase responsible for processing these proteins has not been identified. This report describes the identification of a prepilin peptidase from the V. cholerae genomic database by virtue of its homology with the PilD prepilin peptidase of Pseudomonas aeruginosa. Plasmid disruption or deletion of this peptidase gene in either EI Tor or classical V. cholerae O1 biotype strains results in a dramatic decrease in cholera toxin secretion. In the case of the EI Tor biotype mutants, surface expression of the type 4 pilus responsible for mannose-sensitive haemagglutination is abolished. The cloned V. cholerae peptidase processes either EpsI or MshA preproteins when co-expressed in E. coli. Mutation of the V. cholerae peptidase gene also results in a defect in virulence and decreased levels of OmpU. The V. cholerae peptidase gene sequence shows 80% homology with the Vibrio vulnificus VvpD type 4 prepilin peptidase required for pilus assembly and cytolysin secretion in V. vulnificus. Accordingly, the V. cholerae type 4 prepilin peptidase required for pilus assembly and cholera toxin secretion has been designated VcpD.

Adhesins, Bacterial↗
PubMed1998

The Vibrio cholerae mannose-sensitive hemagglutinin is the receptor for a filamentous bacteriophage from V. cholerae O139.

We previously isolated from a 1994 isolate of Vibrio cholerae O139 a filamentous lysogenic bacteriophage, choleraphage 493, which inhibits pre-O139 but not post-O139 El Tor biotype V. cholerae strains in plaque assays. We investigated the role of the mannose-sensitive hemagglutinin (MSHA) type IV pilus as a receptor in phage 493 infection. Spontaneous, Tn5 insertion, and mshA deletion mutants are resistant to 493 infection. Susceptibility is restored by mshA complementation of deletion mutants. Additionally, the 493 phage titer is reduced by adsorption with MSHA-positive strains but not with a DeltamshA1 strain. Monoclonal antibody against MSHA inhibits plaque formation. We conclude that MSHA is the receptor for phage 493. The emergence and decline of O139 in India and Bangladesh are correlated with the susceptibility and resistance of El Tor strains to 493. However, mshA gene sequences of post-O139 strains are identical to those of susceptible pre-O139 isolates, indicating that phage resistance of El Tor is not due to a change in mshA. Classical biotype strains are (with rare exceptions) hemagglutinin negative and resistant to 493 in plaque assays. Nevertheless, they express the mshA pilin gene. They can be infected with 493 and produce low levels of phage DNA, like post-O139 El Tor strains. Resistance to 493 in plaque assays is thus not equivalent to resistance to infection. The ability of filamentous phages, such as 493, to transfer large amounts of DNA provides them, additionally, with the potential for quantum leaps in both identity and pathogenicity, such as the conversion of El Tor to O139.

Bacterial Proteins↗
PubMed1997

Thrombolysis and endovascular stent placement for inferior vena caval thrombosis in a liver transplant recipient.

BACKGROUND: Vascular complications remain an important cause of postoperative morbidity in liver transplant patients. Herein, we present an unusual case of nonanastomotic inferior vena cava (IVC) stenosis in a patient with a "piggyback" caval anastomosis. METHODS: A 59-year-old woman underwent liver transplantation using a piggyback IVC anastomosis. Her postoperative course was complicated by IVC thrombosis. Catheter-directed thrombolysis, followed by balloon angioplasty and intravascular stent placement, was used to recanalize the IVC and treat a severe retrohepatic IVC stenosis. RESULTS: After 46 hr of catheter-directed urokinase infusion, there was clot lysis and identification of a severe stenosis in the retrohepatic IVC. The lesion was extremely resistant to balloon dilatation alone and a 22-mm-diameter intravascular stent was placed. Simultaneous dilatation of three high-pressure balloons was necessary for maximal stent expansion. The patient remains asymptomatic with no evidence of IVC compromise through 20 months of follow-up. CONCLUSIONS: IVC stenosis and thrombosis after liver transplantation may be treated favorably in some patients using catheter-directed thrombolytic therapy followed by balloon dilatation and/or stent placement.

Angioplasty, Balloon↗
PubMed1997

The prediction of risk of recurrence and time to recurrence of hepatocellular carcinoma after orthotopic liver transplantation: a pilot study.

Orthotopic liver transplantation (OLTx) in the presence of hepatocellular carcinoma (HCC) has been complicated by high recurrence rates. The ability to determine the risk and timing of HCC recurrence on an individual basis would greatly aid in the candidate selection process resulting in a more efficient use of donated organs and allow the individualization and better evaluation of adjuvant chemotherapy. The 214 patients who underwent OLTx in the presence of HCC were analyzed. From the 178 patients who survived more than 150 days, 71 (40%) have suffered HCC recurrence. Based on five risk factors, that is, gender, tumor number, lobar tumor distribution, tumor size, grade of vascular invasion, artificial neural network models predicting the likelihood of HCC recurrence within 1, 2, and 3 consecutive years after transplantation were developed. Based on model predictions, those combinations of risk factors that should/should not lead to recurrence were generated, allowing stratification of patients into the following three groups: 1) patients who should not suffer HCC recurrence and who should not need adjuvant therapy, 2) patients who will suffer recurrence and for whom postoperative chemotherapy significantly prolonged survival (but did not prevent recurrence), and 3) patients who may or may not suffer HCC recurrence and whose recurrence may be prevented by adjuvant chemotherapy. The outcome of OLTx for patients with HCC can be prognosticated based on a number of clinical variables. If verified through multicenter trials, these models could be made available to transplantation programs performing OLTx in the presence of HCC.

Adolescent↗