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Biomedical subjects

Y Fong

Publications and source records attributed to Y Fong.

At least 91 records · Page 5Linked to original sources
PubMed1999

Surgical treatment of malignant liver tumours.

Surgical resection is the mainstay of treatment for malignant liver tumours and offers the only chance of cure. Advances in radiological imaging, surgical technique and peri-operative management have enabled liver resection to be performed safely. Partial hepatectomy is indicated for the treatment of hepatocellular carcinoma and hepatic metastases from colorectal cancer. In addition, it may be utilized for selected patients with liver metastases from other primary tumours. Total hepatectomy with transplantation may be of benefit in some patients with unresectable neuroendocrine metastases or small hepatocellular carcinomas. The role of cryosurgery has not been precisely defined, and it needs to be compared with other palliative therapies such as ethanol injection and hepatic artery embolization.

Carcinoma, Hepatocellular↗
PubMed1999

Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi-mutated herpes simplex virus type-1 (G207).

G207 is a multi-mutated, replication-competent type-1 herpes simplex virus designed to target, infect, and lyse neurological tumors. This study examines the feasibility of using G207 in the treatment of human colorectal cancer and defines the biological determinants of its antitumor efficacy. This virus was tested on five human colorectal cancer cell lines in vitro to determine efficacy of infection and tumor cell kill. These results were correlated to measures of tumor cell proliferation. In vivo testing was performed through direct injections of G207 into xenografts of human colorectal cancer tumors grown in flanks of athymic rats. To evaluate an alternate method of administration, hepatic portal vein infusion of G207 was performed in a syngeneic model of liver metastases in Buffalo rats. Among the five cell lines tested, infection rates ranged between 10% and 90%, which correlated directly with S-phase fraction (8.6%-36.6%) and was proportional to response to G207 therapy in vitro (1%-93%). Direct injection of G207 into nude rat flank tumors suppressed tumor growth significantly vs. control (0.58 +/- 0.60 cm(3) vs. 9.16 +/- 3.70 cm(3), P<0. 0001). In vivo tumor suppression correlated with in vitro effect. In the syngeneic liver tumor model, portal infusion resulted in significant reduction in number of liver nodules (13 +/- 10 nodules in G207-treated livers vs. 80 +/- 30 nodules in control livers, P<0.05). G207 infects and kills human colorectal cancer cells efficiently. In vitro cytotoxicity assay and tumor S-phase fraction can be used to predict response to treatment in vivo. This antineoplastic agent can be delivered effectively by both direct tumor injection and regional vascular infusion. G207 should be investigated further as therapy for colorectal cancer and liver metastases.

Animals↗
PubMed1999

An analysis of 412 cases of hepatocellular carcinoma at a Western center.

OBJECTIVE: Using a large single-institution experience at a Western referral center, the authors examine partial hepatectomy as treatment of hepatocellular carcinoma and relate treatment outcomes to clinical parameters, including the etiology of underlying cirrhosis. METHODS: Four hundred and twelve patients seen between December 1991 and January 1998 were identified in a prospective database. Data about the surgical procedure, perioperative complications, and long-term outcome were examined. RESULTS: One hundred twenty-six patients did not have underlying cirrhosis. Of the 286 patients with cirrhosis, 119 were the result of hepatitis B, 39 hepatitis C, 36 both B and C, 43 ethanol abuse, and the remainder other causes. Two hundred forty-three patients underwent surgical exploration, and 154 patients underwent hepatic resection. Seven (4.5%) died from the surgery. One hundred forty-three patients were treated by ablative methods. Patients with cirrhosis had smaller tumors but nevertheless had a lower resectability rate. Neither the presence of cirrhosis nor the etiology of the cirrhosis altered the perioperative morbidity or mortality rate. The greatest determinant of long-term outcome was resectability. The size of the lesion, an alpha-fetoprotein level >2000 ng/ml, and vascular invasion were also determinants of poor outcome. The presence of cirrhosis was a detrimental factor when analysis was stratified for size of tumor. The cause of cirrhosis did not influence the long-term outcome. The 5-year survival rate was 57% for patients with resected lesions <5 cm and 32% for patients with tumors >10 cm. CONCLUSION: Partial hepatectomy is safe, effective, and potentially curative therapy for hepatocellular carcinoma. The presence of cirrhosis did not affect the surgical mortality rate but did affect the long-term survival rate. The cause of cirrhosis did not influence outcome. As treatment for small hepatocellular carcinomas, partial hepatectomy produces results similar to those of transplantation. For patients with large tumors who are poor candidates for transplantation, resection results in long-term survival in one third of patients.

Carcinoma, Hepatocellular↗
PubMed1999

Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases.

OBJECTIVE: There is a need for clearly defined and widely applicable clinical criteria for the selection of patients who may benefit from hepatic resection for metastatic colorectal cancer. Such criteria would also be useful for stratification of patients in clinical trials for this disease. METHODS: Clinical, pathologic, and outcome data for 1001 consecutive patients undergoing liver resection for metastatic colorectal cancer between July 1985 and October 1998 were examined. These resections included 237 trisegmentectomies, 394 lobectomies, and 370 resections encompassing less than a lobe. The surgical mortality rate was 2.8%. RESULTS: The 5-year survival rate was 37%, and the 10-year survival rate was 22%. Seven factors were found to be significant and independent predictors of poor long-term outcome by multivariate analysis: positive margin (p = 0.004), extrahepatic disease (p = 0.003), node-positive primary (p = 0.02), disease-free interval from primary to metastases <12 months (p = 0.03), number of hepatic tumors >1 (p = 0.0004), largest hepatic tumor >5 cm (p = 0.01), and carcinoembryonic antigen level >200 ng/ml (p = 0.01). When the last five of these criteria were used in a preoperative scoring system, assigning one point for each criterion, the total score was highly predictive of outcome (p < 0.0001). No patient with a score of 5 was a long-term survivor. CONCLUSION: Resection of hepatic colorectal metastases may produce long-term survival and cure. Long-term outcome can be predicted from five criteria that are readily available for all patients considered for resection. Patients with up to two criteria can have a favorable outcome. Patients with three, four, or five criteria should be considered for experimental adjuvant trials. Studies of preoperative staging techniques or of adjuvant therapies should consider using such a score for stratification of patients.

Adult↗
PubMed1999

Nutritional and metabolic aspects of gastrointestinal cancer.

The profound impact of nutrition and nutritional support on the development and clinical outcome of gastrointestinal cancer is undeniable. However, scientific investigation into this area is recent, and many questions remain unanswered. While the importance of 'good nutrition' is unchallenged, details relating to which patients should receive nutritional support, when they should receive it, and what type of support they should receive are not known. Recent prospective randomized clinical trials and meta-analysis have provided conflicting results. This review summarizes the results of the published studies that have addressed these issues, and provides specifics regarding the current role of nutritional support in clinical care, and the prospects for future research.

Gastrointestinal Neoplasms↗
PubMed1999

Sequence and phylogenetic analysis of the SNF4/AMPK gamma subunit gene from Drosophila melanogaster.

To optimize gene expression under different environmental conditions, many organisms have evolved systems which can quickly up- and down-regulate the activity of other genes. Recently, the SNF1 kinase complex from yeast and the AMP-activated protein kinase complex from mammals have been shown to represent homologous metabolic sensors that are key to regulating energy levels under times of metabolic stress. Using heterologous probing, we have cloned the Drosophila melanogaster homologue of SNF4, the noncatalytic effector subunit from this kinase complex. A sequence corresponding to the partial genomic sequence as well as the full-length cDNA was obtained, and shows that the D. melanogaster SNF4 is encoded in a 1944-bp cDNA representing a protein of 648 amino acids (aa). Southern analysis of Drosophila genomic DNA in concert with a survey of mammalian SNF4 ESTs indicates that in metazoans, SNF4 is a duplicated gene, and possibly even a larger gene family. We propose that one gene copy codes for a short (330 aa) protein, whereas the second locus codes for a longer version (<410 aa) that is extended at the carboxy terminus, as typified by the Drosophila homologue presented here. Phylogenetic analysis of yeast, invertebrate, and multiple mammalian isoforms of SNF4 shows that the gene duplication likely occurred early in the metazoan lineage, as the protein products of the different loci are relatively divergent. When the phylogeny was extended beyond the SNF4 gene family, SNF4 shares sequence similarity with other cystathionine-beta-synthase domain-containing proteins, including IMP dehydrogenase and a variety of uncharacterized Methanococcus proteins.

AMP-Activated Protein Kinases↗
PubMed1999

Hepatocellular carcinoma: MR imaging findings in cirrhotic livers and noncirrhotic livers.

PURPOSE: To compare the magnetic resonance (MR) imaging findings of primary hepatocellular carcinoma (HCC) in cirrhotic versus noncirrhotic livers. MATERIALS AND METHODS: MR images in 36 patients with HCC (30 men and she women aged 42-84 years [mean age, 65 years]) were retrospectively reviewed. The number and size of hepatic lesions were assessed. Lesion margins were categorized as well circumscribed or ill defined. The presence of a capsule, intratumoral high signal intensity on T1-weighted MR images, and a stellate scar were determined. RESULTS: Eleven (31%) patients had MR imaging evidence of cirrhosis, and 25 (69%) did not: Lesions in cirrhotic livers differed significantly from those in noncirrhotic livers in terms of size (22 cm2 vs 99 cm2, P < .05), frequency of a solitary lesion (27% vs 72%, P < .05), and frequency of a central scar (6% vs 50%, P < .05). There was no difference between the cirrhotic and noncirrhotic livers with regard to tumor margin, intratumoral high signal intensity on T1-weighted images, or tumor capsule. CONCLUSION: Differences exist in the MR imaging appearance of HCC between patients with and those without cirrhosis, although there is overlap of imaging findings.

Adult↗
PubMed1999

Recurrent gallbladder carcinoma along laparoscopic cholecystectomy port tracks: CT demonstration.

PURPOSE: To describe the computed tomographic (CT) appearance of recurrent gallbladder carcinoma along port tracks after laparoscopic cholecystectomy and to assess the effect of recurrence on patient care. MATERIALS AND METHODS: Seventeen abdominal CT scans in 16 of 19 consecutive patients who underwent hepatic resection for gallbladder carcinoma diagnosed at laparoscopic cholecystectomy were reviewed retrospectively. Medical records were reviewed to determine the clinical effect of tumor recurrence along a port track. RESULTS: CT revealed 12 tumor recurrences along laparoscopic port tracks in six (32%) patients (mean, two recurrences per patient; range, one to four per patient). Eight (67%) CT-depicted recurrences appeared homogeneous, and nine (75%) directly involved subjacent omental fat. The mass was the only site of recurrence at CT in two (33%) patients. The presence of an abdominal wall tumor recurrence affected patient care in four (67%) of six patients. Histopathologic examination results confirmed recurrent tumor in all five (100%) patients who underwent biopsy. CONCLUSION: Tumor recurrence along port tracks is a potential complication of laparoscopic cholecystectomy when gallbladder carcinoma is present, even after subsequent hepatic resection is performed for attempted cure. Recurrences appear as a new or enlarging abdominal wall mass, often involving subjacent omental fat, and may be the only site of recurrent disease at CT. Demonstration of abdominal wall tumor recurrence affects patient care.

Abdominal Muscles↗
PubMed1999

The critically ill patient after hepatobiliary surgery.

BACKGROUND: We analyzed the causes and results of utilization of critical care services in the special care unit in patients after surgical procedures performed by the hepatobiliary surgical service during a 23-month period. RESULTS: Thirty-two of 537 patients (6.0%) required postoperative admission to the special care unit. Twenty-one patients were admitted directly from operating room or from recovery room because of inability to wean from ventilator (n = 10), hypovolemic shock (n = 4), myocardial ischemia or infarction (n = 2), sepsis (n = 2), upper gastrointestinal bleeding (n = 2), and acute renal failure (n =1). Eleven postoperative patients were admitted from floor care for respiratory failure (n = 4), cardiac dysrhythmia or infarction (n = 4), sepsis (n = 2), and upper gastrointestinal bleeding (n = 1). Thirty-eight per cent of patients (n = 12) admitted to the special care unit after surgery died. By multivariate analysis, total postoperative stay in the special care unit that was greater than median total duration of stay of 4.5 days was the only independent predictor of mortality (P = 0.041). CONCLUSIONS: Respiratory failure was the predominant component of all complications after hepatobiliary surgery. No clinically useful predictors of eventual outcome could be identified.

Journal Article↗
PubMed1999

Surgical therapy of hepatic colorectal metastasis.

The liver is a common site of metastases from colorectal cancer. The data are convincing that liver resection is a safe and effective therapy for such metastatic disease. Even extensive resections can be performed with a less than 5% mortality rate at major centers and a 5-year survival rate of 30% to 40%. This review examines factors important for patient selection for liver resection and proposes a prognostic scoring system that may help in patient selection. For unresectable disease, many methods for ablating tumors are now available that will likely prove to be useful adjuncts to current treatment.

Colorectal Neoplasms↗
PubMed1999

Herpes simplex virus (HSV)-mediated ICAM-1 gene transfer abrogates tumorigenicity and induces anti-tumor immunity.

BACKGROUND: Costimulatory and cellular adhesion molecules are thought to be essential components of antigen presentation in the immune response to cancer. The current studies examine gene transfer utilizing herpes viral amplicon vectors (HSV) to direct surface expression of adhesion molecules, and specifically evaluate the potential of a tumor-expressing intercellular adhesion molecule-1 (ICAM-1) to elicit an anti-tumor response. MATERIALS AND METHODS: The human ICAM-1 (hICAM1) gene was inserted into an HSV amplicon vector and tested in a transplantable rat hepatocellular carcinoma and in a human colorectal cancer cell line. Cell surface ICAM-1 expression was assessed by flow cytometry. Lymphocyte binding to HSV-hICAM1-transduced cells was compared with that to cells transduced with HSV not carrying the ICAM gene. Tumorigenicity of HSV-hICAM1-transduced tumor cells were tested in syngeneic Buffalo rats. Additionally, immunization with irradiated (10,000 rads) HSV-hICAM1-transduced tumor cells was performed to determine its effect on tumor growth. RESULTS: A 20-min exposure of tumor cells at a multiplicity of infection (MOI) of 1 resulted in high-level cell surface expression of human ICAM in approximately 25% of tumor cells. Transduced rat or human tumor cells exhibited significantly enhanced binding of lymphocytes (p < 0.05). HSV-hICAM1-transduced cells elicited an increase in infiltration by CD4(+) lymphocytes in vivo and exhibited decreased tumorigenicity. Immunization with irradiated HSV-hICAM1-transduced cells protected against growth of subsequent injected parental tumor cells. CONCLUSIONS: HSV amplicon-mediated gene transfer is an efficient method for modifying the cell surface expression of adhesion molecules. Increased tumor expression of ICAM-1 represents a promising immune anti-cancer strategy.

Animals↗
PubMed1999

Imaging of hepatobiliary neoplasms.

Improvements in imaging have markedly improved the ability to detect hepatobiliary masses. The radiologic features of a lesion when considered in the context of the medical history, physical findings, and laboratory data can often provide a diagnosis. Investigative modalities can accurately stage hepatobiliary tumors and determine their resectability so that the patient may be offered appropriate therapeutic interventions. This article summarizes the essential imaging techniques and their application to common hepatobiliary neoplasms.

Angiography↗
PubMed1998

Gallbladder carcinoma discovered during laparoscopic cholecystectomy: aggressive reresection is beneficial.

BACKGROUND: This study attempted to determine whether aggressive surgical therapy is warranted after gallbladder carcinoma is discovered during or after laparoscopic cholecystectomy. METHODS: The clinical course and outcome of 42 consecutive patients with laparoscopically discovered gallbladder carcinoma seen over a 5-year period at a tertiary referral center were examined. Nine of the patients had TNM classified T2 tumors and 32 had full thickness penetration of the gallbladder including 16 T3 and 16 T4 tumors. RESULTS: At reexploration, 22 of the patients were found to have lymph node, peritoneal, or bilateral liver disease precluding reresection. Nineteen patients underwent liver resection (13 trisegmentectomies and 6 bisegmentectomies), portal lymphadenectomy, and hepaticojejunostomy as the definitive surgical procedure for the carcinoma. There was 1 perioperative death, and the median hospital stay was 11 days (range, 6-28 days). At last follow-up 17 of the 22 nonresected patients had died, with a median survival of 5 months. With a follow-up of 16 months, only 3 of the resected patients had died. CONCLUSIONS: The authors conclude that aggressive resection of gallbladder carcinoma discovered laparoscopically is safe and effective.

Adult↗
PubMed1998

The effects of hepatic cryosurgery on tumor growth in the liver.

BACKGROUND: The effects of hepatic cryosurgery on residual hepatic tumor growth, and on tumor immunity, have not been determined. MATERIALS AND METHODS: Two experiments were performed. In both, animals (n = 10 per group) had solitary left lobe hepatomas established, and underwent left lobectomy, cryoablation, or control laparotomy. Experiment I: immediately after tumor treatment, intraportal challenge of hepatoma cells was performed to evaluate for the effects of treatment on residual hepatic tumor growth. Experiment II: animals were challenged 14 days after tumor treatment, and splenocyte cytotoxicity assays were performed to evaluate for tumor immunity. Hepatic tumor nodules were counted 3 weeks after challenge in both experiments. RESULTS: In animals challenged immediately after tumor treatment, the mean number of liver nodules at 3 weeks was similar between control and cryoablation groups (65 +/- 13 vs 115 +/- 38, P = 0.17). Animals that had undergone resection, however, had a significant increase in the mean number of nodules as compared to cryoablation (278 +/- 74 vs 115 +/- 38, P = 0. 04) and control (278 +/- 74 vs 65 +/- 13, P = 0.002) animals. In addition, only resection animals had elevation in serum levels of the growth factor FGF-basic, 48 h after treatment (mean = 30 +/- 14 pg/ml). In animals challenged 14 days following treatment, all groups had similar numbers of nodules (resection vs cryoablation, P = 0.8). Splenocyte cytotoxicity was not increased after cryosurgical treatment. CONCLUSIONS: Unlike partial hepatectomy, cryoablation of hepatomas in rats does not accelerate residual tumor growth in the liver or result in production of the growth factor FGF-basic. We did not find evidence for the development of tumor immunity following cryosurgery.

Alanine Transaminase↗
PubMed1998

In vitro detection of occult bone marrow metastases in patients with colorectal cancer hepatic metastases.

PURPOSE: The purpose of this study was to assess the immunocytochemical status of bone marrow aspirates from patients with clinically isolated hepatic metastases to test the hypothesis that such findings would allow improved patient selection for liver-directed treatment. METHODS: All patients had biopsy-proven or presumed colorectal cancer metastatic to the liver and were scheduled for an operative procedure for hepatic resection or for hepatic artery catheter and chemotherapy pump implant. Immunocytochemical analysis of bone marrow aspirate smears was performed with a panel of monoclonal antibodies directed toward cytokeratins, Lewis Y antigen and A-33 colorectal epitopes. RESULTS: Data from 80 patients indicated that bone marrow reactivity was present in 9.5 percent of those with resectable hepatic metastases and in 34 percent of those not resected (P = 0.03). No single monoclonal antibody or combination produced better discrimination. CONCLUSIONS: Presence or absence of presumed occult colorectal cancer cells in the bone marrow of patients with isolated hepatic metastases is biologically interesting, but not useful in selecting or altering patient management.

Antibodies, Monoclonal↗
PubMed1998

Intrahepatic biliary enteric bypass provides effective palliation in selected patients with malignant obstruction at the hepatic duct confluence.

BACKGROUND: Palliating the effects of biliary obstruction is a major goal of therapy in patients with cancer at the hepatic duct confluence. This study was undertaken to evaluate the effectiveness of intrahepatic biliary-enteric bypass to either the segment III duct or the right sectoral hepatic ducts in patients with unresectable hilar cholangiocarcinoma or gallbladder carcinoma. METHODS: From December 1991 to October 1996, 55 consecutive bypass procedures were prospectively evaluated in patients with unresectable hilar cholangiocarcinoma or gallbladder cancer. Patients were divided into three groups based on the primary tumor and the type of bypass performed: group 1A, cholangiocarcinoma/segment III bypass (n = 20); group 1B, cholangiocarcinoma/right sectoral hepatic duct bypass (n = 14); group 2, gallbladder cancer/segment III bypass (n = 21). RESULTS: Mean hospital stay (14+/-2 days) and mean blood loss (629+/-84 mL) were similar among the three groups. Perioperative death occurred in 6 patients (11%): 0 in group 1A, 3 each in groups 1B and 2. All survivors had relief of jaundice and pruritus after bypass. Complications occurred in 25 patients (45%). Preoperative transhepatic biliary drainage, performed in 14 patients prior to referral, was associated with a higher incidence of contaminated bile, greater operative blood loss, and postoperative biliary leak that was less likely to resolve spontaneously. Median survival in patients with cholangiocarcinoma (groups 1A and 1B) was 52 weeks and was unaffected by the type of bypass performed. By contrast, median survival in patients with gallbladder cancer (group 3) was 20 weeks; all but 3 died within 32 weeks of surgery. In patients with cholangiocarcinoma, the 1-year bypass patency was 80% in group 1A (segment III bypass) and 60% in group 1B (right sectoral hepatic duct bypass). Overall, there were 9 late bypass failures (18%) requiring reintervention. CONCLUSIONS: Intrahepatic biliary-enteric bypass effectively relieves symptoms due to malignant hilar obstruction. In patients with cholangiocarcinoma, segment III bypass provides excellent palliation with relatively few late complications and can be performed with minimal morbidity and mortality. Bypass to the right sectoral hepatic ducts, on the other hand, is associated with significant procedure-related morbidity and mortality and more late complications. Patients with gallbladder cancer, because of their poor survival, are probably better palliated by percutaneous biliary stenting.

Anastomosis, Surgical↗
PubMed1998

Use of preoperative autologous blood donation in liver resections for colorectal metastases.

BACKGROUND: Transfusion of allogeneic blood is associated with risks of human immunodeficiency virus and hepatitis transmission, transfusion reactions, and other potential immunologic and infectious complications. To determine if predonation of autologous blood impacts upon transfusion practice and clinical outcome following liver resection, clinical records of 379 consecutive patients undergoing hepatic resection for metastases of colorectal cancer were identified from the prospective hepatobiliary database and reviewed. METHODS: Of the 379 hepatic resections performed for colorectal metastases between January 1991 and January 1996, 240 (63%) were hepatic lobectomy or trisegmentectomy. Thirty-two percent of patients (123 of 379) agreed to preoperative blood donation (POBD), and their clinical characteristics including age, preoperative hemoglobin, and operative mortality were comparable with those of patients without POBD. Liver resections were carried out using standard vascular inflow and outflow control. Parenchymal transections were performed bluntly with maintenance of low central venous pressure (0 to 5 cm H2O). No vascular isolation or normovolemic hemodilution was used intraoperatively. All erythrocyte transfusions during the entire hospital stay were considered and compared between the two groups. RESULTS: Forty-five percent of patients (172 of 379) received blood transfusions during or after liver resections, of which 61% (105 of 172) required only 1 or 2 units. Only 17% of the POBD group required allogeneic blood. This was significantly less than the group without POBD (43%, P <0.01). There was no significant difference in the operative mortality (2.3% versus 4.9%, P = 0.2) and the median survival (50 versus 40 months, P = 0.3). CONCLUSIONS: Major hepatic resections using current surgical techniques can be performed safely with low blood loss and transfusion is required for only a minority of patients. POBD further reduces transfusion requirement.

Adult↗