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Biomedical subjects

Y Fong

Publications and source records attributed to Y Fong.

At least 109 records · Page 6Linked to original sources

Efficient gene transfer to human squamous cell carcinomas by the herpes simplex virus type 1 amplicon vector.

BACKGROUND: This study evaluates the efficiency of herpes simplex virus (HSV) mediated gene transfer in human squamous cell carcinoma (SCC) cell lines in vitro and in vivo when delivered by selective intra-arterial perfusion. METHODS: Human head and neck SCC were exposed to HSV-LacZ and HSV-interleukin-2 (IL-2) and gene transfer and expression assessed by X-gal staining and enzyme-linked immunosorbent assay, respectively. Hamster cheek pouch tumors were perfused with HSV-LacZ or HSV-IL-2, by microcannulating the external carotid artery, and gene transfer determined. RESULTS: A ratio of 5 viral particles per tumor cell achieved gene transfer rates exceeding 50%. Interleukin-2 levels of 287 +/- 17 to 424 +/- 8.4 ng per million cells were achieved at a ratio of 2 viral particles per tumor cell. Selective intra-arterial perfusion of the HSV-IL-2 vector yielded IL-2 levels of 45.8 +/- 17.0 pg per g tumor. CONCLUSIONS: HSV amplicon vectors are efficient vehicles for gene transfer in vitro in human head and neck SCC cell lines and in vivo when introduced by selective intra-arterial perfusion.

Animals↗

Characterization of a new EBV-associated nasopharyngeal carcinoma cell line.

Only a few reports exist of cytogenetic studies in nasopharyngeal carcinoma (NPC), probably because of the technical limitations of culturing solid tumors. We established a cell line (cell-666) that was derived from an NPC xenograft growing in athymic nude mice. Epstein-Barr virus (EBV) infection is one of the important etiologic factors of NPC. This cell line has been shown to have the consistent presence of EBV by Epstein-Barr virus encoded RNAs (EBER) in situ hybridization. Furthermore, aberrant methylation of 5'CpG island of p16 gene was detected. Thus, this cell line represents a valuable model for the study of NPC tumorigenecity. The karyotype of this newly established cell line is: 45,X,del(X)(q24),-5der(5)(5pter-->5q31::5q13-->+ ++5q31::5p12-->5pter),der(6;?) (q10;p10),add(7)(p22), + 9, del(11)(q13),add(12)(p13),-14,-18,-21, + 2mar. Fluorescence in situ hybridization analyses were performed using whole chromosome painting probes of chromosomes 5, 6, 11, and 12.

Animals↗

Segment-oriented hepatic resection in the management of malignant neoplasms of the liver.

BACKGROUND: Improvements in the understanding of intrahepatic anatomy and radiographic technology have facilitated a segment-oriented approach to liver resection. This approach involves the resection of isolated anatomic segments or sectors of the liver as dictated by the extent of the intrahepatic pathology. Segment-oriented resection allows maximal conservation of normal liver parenchyma while clearing tumor. This report describes the technical features and the results of a prospective evaluation of segmental and sectoral resections in the treatment of malignant hepatic neoplasms. STUDY DESIGN: Patients with malignant hepatic neoplasms that were treated with a segment-oriented hepatic resection were identified from a prospective clinical data base. After undergoing segment-oriented liver resection, the patients were followed at regular intervals. Recurrent disease was the end point of the study. Followup is reported at a median of 12 months. This review outlines the technique of resection, intraoperative events, operating time, blood loss, and the ability to obtain negative resection margins. RESULTS: During the 5-year period between July 1992 and July 1997, 400 patients underwent liver resection for metastatic neoplasms and hepatocellular carcinoma (HCC). During this period, 79 patients (20%) were treated with a segment-oriented resection. These patients represent the study group for this report. The overall mortality rate was 2.5%; all postoperative deaths occurred in patients with HCC and cirrhosis. Overall morbidity was 26%. The median hospital stay was 8 days. Mean transfusion requirements were 1.0 +/- 0.3 U of packed red blood cells. Patients with HCC showed a greater transfusion requirement than did patients without HCC: 2.7 +/- 1.2 U versus 0.6 +/- 0.2 U (p < 0.05). Of the patients without HCC, 17% required transfusion. During the 12-month median followup period, the overall disease recurrence rate was 23%. Disease recurred at the hepatic-resection margin in 2.5% of the patients. CONCLUSIONS: Segmental resection is a safe technique that allows complete resection of liver tumors with preservation of normal liver parenchyma. Segmental resection is particularly useful for patients with HCC and patients undergoing repeat liver resections or bilobar resections.

Adult↗

Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction.

BACKGROUND: We have previously demonstrated that maintenance of a low central venous pressure (LCVP) combined with extrahepatic control of venous outflow reduced the overall blood loss during major hepatic resections. This study examined the overall outcomes and, in particular, renal morbidity associated with a large series of consecutive major liver resections performed with this approach. In addition, the rationale for the anesthetic management to maintain LCVP was carefully reviewed. STUDY DESIGN: All major hepatectomies performed between December 1991 and April 1997 were reviewed. The prospective Hepatobiliary Surgical Service database was merged with the Memorial Hospital Laboratory and Blood Bank databases to yield the nature of the operation, blood loss, blood product transfusions, outcomes, and levels of preoperative, postoperative, and discharge serum creatinine and blood urea nitrogen. RESULTS: A total of 496 LCVP-assisted major liver resections were performed, with no intraoperative deaths and an in-hospital mortality rate of 3.8%. The median blood loss was 645 mL. Sixty-seven percent of the patients did not require perioperative blood transfusion during surgery and the immediate 12 hours after surgery. The median number of blood transfusions was 2. Only 3% of the patients experienced a persistent and clinically significant increase in serum creatinine possibly attributable to the anesthetic technique. Renal failure directly attributable to the anesthetic technique did not occur. CONCLUSIONS: Major resection with LCVP allowed easy control of the hepatic veins before and during parenchymal transection. The anesthetic technique, designed to maintain LCVP during the critical stages of hepatic resection, not only helped to minimize blood loss and mortality but also preserved renal function.

Blood Loss, Surgical↗

Surgical treatment of 32 patients with peripheral intrahepatic cholangiocarcinoma.

BACKGROUND: Peripheral intrahepatic cholangiocarcinoma (PIC) is an intrahepatic primary liver neoplasm which is clinicopathologically distinct from hepatocellular carcinoma and major duct cholangiocarcinoma. The clinical outcome after resection of these rare tumours is not well documented. METHODS: Review of the hepatic database and tumour registry at Memorial Sloan-Kettering Cancer Center identified 32 cases of PIC resected for cure over a 23-year period. Intrahepatic cholangiocarcinomas with major bile duct involvement were excluded from this analysis. Demographics, pathological features, biochemical markers, operative results and survival were analysed. RESULTS: The majority of patients presented with abdominal pain (n=19). Only two patients had pathological evidence of hepatic cirrhosis. Serum marker levels included 7-fetoprotein (AFP; median 3.7 (range 0-225) ng/ml) and carcinoembryonic antigen (CEA; median 1-6 (range 0-30) ng/ ml). Type of hepatic resection included: wedge (n=2), lobectomy (n=14) and extended lobectomy (n=16). There was one postoperative death. Median follow-up time was 27 months. Median survival was 59 months with an actuarial 5-year survival of 42 per cent. Vascular invasion and intrahepatic satellite lesions were predictors of worse survival (P < 0.05). CONCLUSION: PIC is a rare hepatic primary tumour, which usually presents in non-cirrhotic livers with a normal serum AFP and CEA level. In selected patients, complete surgical resection can be performed safely and is associated with long-term survival.

Aged↗

Pretreatment with IFN-gamma decreases infectious complications after partial hepatectomy in the rat.

Infectious postoperative complications occur commonly after hepatectomy and may lead to a long hospital stay or death. The potential beneficial effects of interferon-gamma (IFN-gamma) in this setting were evaluated in a model of hepatectomy and sepsis in rodents. Incidence of bacterial translocation was measured in animals on days 1, 2, and 5 after partial hepatectomy. Macrophage function was quantified by in vitro tumoricidal activity and superoxide anion (O2-) production. Survival after partial hepatectomy and cecal ligation and puncture (CLP) was recorded. After partial hepatectomy, bacterial translocation was decreased on days 1 and 2 in animals pretreated with IFN-gamma (p < 0.05). Macrophages from animals treated with IFN-gamma had higher in vitro tumoricidal activity and production of O2- (p < 0.05). Hepatectomized animals pretreated with IFN-gamma had an increased survival after CLP (p < 0.05). IFN-gamma may be useful in decreasing the incidence of infectious complications after partial hepatectomy.

Animals↗

Hilar Cholangiocarcinoma: patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical staging system.

OBJECTIVES: To determine the resectability rate for hilar cholangiocarcinoma, to analyze reasons for unresectability, and to devise a presurgical clinical T-staging system. METHODS: Ninety patients with hilar cholangiocarcinomas seen between March 1, 1991, and April 1, 1997, were evaluated. Accurate patterns of disease progression and therapy were evaluable. Disease was staged in 87 patients using extent of ductal tumor involvement, portal vein compromise, and liver atrophy. RESULTS: In 21 patients, disease was deemed unresectable for cure at presentation. In 39 patients, disease was found to be unresectable at laparotomy, 23 secondary to nodal (N2) or distant metastases. Unresectability was the result of metastases in 52% and of locally advanced disease in 28%. Thirty patients (33%) had resection of all gross disease, and 25 of these (83%) had negative histologic margins. Twenty-two patients underwent partial hepatectomy. The 30-day mortality rate was 7%. Projected survival is greater than 60 months in those with a negative histologic margin, with a median follow-up of 26 months. A presurgical T-staging system allows presurgical selection for therapy, predicts partial hepatectomy, and offers an index of prognosis. CONCLUSIONS: In half the patients, unresectability is mainly the result of intraabdominal metastases. Presurgical imaging predicts unresectability based on local extension but is poor for assessing nodal metastases. In one third of patients, disease can be resected for cure with a long median survival. Curative resection depends on negative margins, and hepatic resection is necessary to achieve this. The T-staging system correlates with resectability, the need for hepatectomy, and overall survival.

Bile Duct Neoplasms↗

Tumor involvement in hepatic veins: comparison of MR imaging and US for preoperative assessment.

PURPOSE: To compare use of magnetic resonance (MR) imaging and ultrasonography (US) for diagnosis of vascular involvement by tumor at the hepatic vein confluence. MATERIALS AND METHODS: Thirty-seven consecutive patients with tumors at the hepatic vein confluence were prospectively evaluated with spin-echo and gradient-echo MR imaging and gray-scale and Doppler US. Encasement, thrombosis, occlusion, and nonvisualization were considered to be evidence of vascular involvement. Imaging results were compared with surgical and pathologic examination findings in 27 patients who underwent resection. RESULTS: Sixteen hepatic veins (nine right, four middle, three left) were seen to be involved at surgery. Twelve of 16 involved veins were identified at MR imaging (75% sensitivity, 98% specificity, 92% positive predictive value, 94% negative predictive value). Thirteen of 16 involved veins were detected at US (81% sensitivity, 97% specificity, and 87% positive and 95% negative predictive values). There was one false-positive diagnosis of inferior vena cava involvement at both MR imaging and US. Ten patients had unresectable disease. One patient had motion artifact on MR images; in the remaining nine patients, MR imaging and US yielded identical findings at 26 of 27 hepatic vein sites. CONCLUSION: MR imaging and US provide comparable results for assessment of hepatic vein involvement by tumor.

Bile Duct Neoplasms↗

Complex postcholecystectomy biliary disorders: preliminary experience with evaluation by means of breath-hold MR cholangiography.

PURPOSE: To assess preliminary experience with breath-hold single-shot fast spin-echo magnetic resonance (MR) cholangiography in complex postcholecystectomy biliary disorders. MATERIALS AND METHODS: MR cholangiography was performed in 17 consecutive patients referred for specialist surgical evaluation of suspected complex postcholecystectomy biliary disorders. Two readers, unaware of surgical, histopathologic, or other imaging findings, independently reviewed the MR cholangiographic images to assess the presence of biliary occlusion, peribiliary lesions, nonspecific biliary dilatation (biliary dilatation without an abrupt transition in caliber and without a visible underlying cause), bile duct stones, or biliary fistulas. Final diagnoses were established with surgery (n = 9), imaging other than MR (n = 6), and histopathologic review of the initial surgical specimen (n = 2). RESULTS: Final diagnoses were biliary occlusion (n = 8), peribiliary lesions (n = 3), nonspecific biliary dilatation (n = 3), bile duct stones (n = 2), and biliary-colonic fistula (n = 1). The two readers correctly categorized these diagnoses in 15 (88%) and 13 (76%) of the 17 cases, with excellent interobserver agreement (kappa = 0.82). CONCLUSION: Single-shot fast spin-echo MR cholangiography is an accurate, noninvasive modality for the assessment of complex postcholecystectomy biliary disorders.

Adult↗

Isolated hepatic splenosis: first reported case.

Splenosis is the autotransplantation of splenic tissue, most commonly seen after traumatic splenic rupture and splenectomy. Post-traumatic splenosis is often considered a rare entity, but is probably underreported because of its asymptomatic nature. We describe the first reported case of splenosis presenting as a liver mass, indistinguishable from a liver tumor by standard preoperative evaluation. The pathophysiology, evaluation and management of splenosis is discussed as well as the decision to resect a benign appearing liver mass.

Adult↗

Neoplastic pancreaticobiliary duct obstruction: evaluation with breath-hold MR cholangiopancreatography.

OBJECTIVE: The purpose of this study was to investigate the use of breath-hold single-shot fast spin-echo MR cholangiopancreatography in neoplastic pancreaticobiliary duct obstruction. MATERIALS AND METHODS: Breath-hold MR cholangiopancreatography was performed for preoperative examination of 32 consecutive patients with pathologically confirmed neoplastic obstruction of the biliary tract or pancreatic duct using a single-shot fast spin-echo sequence. Two observers, unaware of clinical or pathologic findings, independently reviewed the MR cholangiopancreatograms to assess level of obstruction and site of underlying tumor. Pathologic diagnoses, based on surgical or CT-guided biopsy specimens, were pancreatic tumor (n = 12), gallbladder cancer (n = 9), intrahepatic cancer (n = 9), and ampullary cancer (n = 2). RESULTS: On the basis of conventional cholangiography, CT, and surgical findings, 20 patients had isolated bile duct obstruction, 11 patients had combined pancreatic and bile duct obstruction, and one patient had isolated pancreatic duct obstruction. Isolated bile duct obstruction was classified as lobar (n = 5), hilar (n = 12), or distal (n = 3). These levels of obstruction were correctly identified in 27 (84%) and 28 (88%) of the 32 cases by the two observers. The site of the underlying tumor was identified in 27 (84%) and 29 (91%) cases by the two observers. Good interobserver agreement was reached for both level of obstruction (kappa = .70) and identification of tumor site (kappa = .75). CONCLUSION: Breath-hold single-shot fast spin-echo MR cholangiopancreatography is accurate in identifying the level of obstruction and the site of underlying tumor in neoplastic pancreaticobiliary duct obstruction, with good interobserver agreement.

Adult↗

Gallbladder cancer: can ultrasonography evaluate extent of disease?

This study reviews the spectrum of sonographic findings in patients with gallbladder cancer, attempts to determine if sonography can identify patients with potentially resectable disease, and emphasizes the limitations of ultrasonography in the evaluation of -gallbladder cancer. Thirty-five consecutive patients with histologically proven gallbladder carcinoma who had preoperative abdominal ultrasonography and surgery were identified. Involvement of the gallbladder and gallbladder fossa, metastases, bile ducts, portal vein, and adjacent lymph nodes was assessed sonographically. The extent of disease and staging as revealed by sonography was compared to operative and surgical pathologic findings. Masses in the gallbladder or gallbladder fossa were present at surgery in 26 patients; 22 (85%) of these masses were shown by sonography. Sonography identified six (67%) of nine cases of pathologically confirmed liver metastases, 11 (79%) of 14 cases of bile duct involvement, and two (67%) of three cases of portal venous involvement by tumor. Sonography revealed lymph node metastases in only five (36%) of 14 patients. None of the 12 cases with peritoneal metastases was identified sonographically. By surgical staging 16 (46%) patients had potentially resectable disease (stage III or less), and 19 (54%) patients had unresectable stage IV disease. Sonography correctly identified 15 (94%) of 16 patients with potentially resectable disease and seven (37%) of 19 patients with advanced disease. Twelve patients with advanced disease were under-staged: nine had peritoneal metastases, two had liver metastases, and one had celiac adenopathy, which was not shown by sonography. In conclusion, sonography is reliable in the detection of a primary gallbladder mass or of local extension of tumor into the liver. However, sonographic findings do not accurately reflect the full extent of disease, and sonography is particularly limited in the diagnoses of metastases to the peritoneum and lymph nodes.

Adult↗

Cytokine gene therapy for human tumors.

Cytokine gene therapy is a potentially powerful antineoplastic strategy. It provides paracrine cytokine secretion in the region of putative tumor antigen that maximizes antitumor immune responses and minimizes systemic toxicity. A wealth of animal experimentation has demonstrated the effectiveness of cytokine gene therapy in a variety of tumor models. Enough evidence has mounted such that human cytokine gene therapy trials are underway throughout the United States and elsewhere.

Cancer Vaccines↗

Partial hepatectomy accelerates local tumor growth: potential roles of local cytokine activation.

BACKGROUND: Surgical excision of liver tumors represents the only curative treatment for primary and metastatic liver malignancies. It has been suspected that hepatectomy may stimulate growth of microscopic tumors. To determine whether local or systemic factors after hepatectomy are responsible for enhancement of tumor growth, the effects of hepatectomy on the experimental growth of liver or pulmonary tumors were examined. METHODS: One hour after injection of 10(6) Morris hepatoma cells into either the portal or femoral vein, which produces isolated liver and lung tumors, respectively, animals were randomized to undergo 0%, 30%, or 70% partial hepatectomy (PH). RESULTS: Animals that underwent portal injection of tumor had significantly increased liver tumor burden after PH (sham, 25 +/- 7 vs PH, 94 +/- 17; p < 0.01), whereas animals that underwent femoral injection had no change in lung tumor burden after PH. PH was associated with significantly increased levels of transforming growth factor-alpha, transforming growth factor-beta, and basic fibroblast growth factor in the liver but not in the lung. CONCLUSIONS: Changes in liver cytokine-growth factor activation may contribute to enhanced tumor growth in the liver after hepatectomy.

Animals↗

Hepatic colorectal metastasis: current status of surgical therapy.

Metastatic colorectal cancer to the liver develops in over 50,000 US patients each year and is rapidly fatal if untreated. Even the most active chemotherapeutic agents rarely prolong survival for more than 3 years. Liver resection is the only potentially curative treatment, affording 5-year survival in one-third of patients. The only absolute contraindications to liver resection are poor general health, clear evidence of wide disease dissemination, or inability to resect all liver disease. Close follow-up is warranted after liver resection since disease recurs in two-thirds of patients and recurrences can be successfully treated, possibly with curative potential. Cryosurgery is a promising ablative modality that needs to be compared to chemotherapy but has not been proven to be curative.

Chemotherapy, Adjuvant↗

Prevention of hepatic tumor metastases in rats with herpes viral vaccines and gamma-interferon.

Previous studies showed that gammaIFN decreases metastatic hepatic tumor growth by stimulating Kupffer cells (KC). The present studies examine whether lymphocyte stimulation via cells engineered to secrete GM-CSF or IL-2 decreases hepatic tumor growth, and whether stimulation of both macrophages and lymphocytes is more effective than either individually. Rats were immunized with irradiated hepatoma cells transduced by herpes viral amplicon vectors containing the genes for GM-CSF, IL-2 or LacZ. On day 18, half of each group was treated with 5 x 10(4) U gammaIFN, or saline intraperitoneally for 3 d. On day 21, all rats received 5 x 10(5) hepatoma cells intrasplenically. On day 41, rats were killed and tumor nodules were counted. Separate rats underwent splenocyte and KC harvest for assessment of lymphocyte- and macrophage-mediated tumor cell kill in vitro. GM-CSF or IL-2 vaccines or gammaIFN decreased tumor nodules significantly (GM-CSF 13+/-4, IL-2 14+/-6 vs. control 75+/-24, P < 0.001). Combination therapy was more effective, and completely eliminated tumor in 4 of 12 IFN-GM-CSF and 8 of 11 IFN-IL-2 animals. Additional rats underwent partial hepatectomy, an immunosuppressive procedure known to accelerate the growth of hepatic tumor, following tumor challenge. Therapy was equally effective in this immunosuppressive setting. Vaccination is associated with enhancement of splenocyte-mediated tumoricidal activity, whereas the effect of gammaIFN is mediated by KC. GM-CSF and IL-2 vaccine therapy and pretreatment with gammaIFN represent effective strategies in reducing hepatic tumor. Combination therapy targets both lymphocytes and macrophages, and is more effective in reducing tumor than either therapy alone.

Animals↗

Hepatic resection for metastatic gynecologic carcinomas.

OBJECTIVE: To report a series of cases of hepatic resection for metastatic gynecologic carcinomas. METHODS: We reviewed the records of all patients who underwent hepatic resection for metachronous liver metastases from gynecologic carcinomas at our institution from 1986 to 1996. RESULTS: Twelve patients were identified with a median age of 60 years (range 30-73 years). The primary sites of carcinoma were as follows: ovary, 7 (58%); cervix, 2 (17%); endometrium, 2 (17%); and fallopian tube, 1 (8%). The median disease-free interval before the diagnosis of liver metastasis was 32 months (range 1-243 months). The types of liver resections were as follows: trisegmentectomy, 4 (33%); lobectomy, 4 (33%); segmentectomy, 3 (25%); and wedge resection, 1 (8%). To remove all visible tumor with adequate margins, additional surgery included the following: resection of a portion of the diaphragm, 5 (42%); wedge resection of the right lung, 3 (25%); resection of a portion of the pericardium, 2 (17%); and adrenalectomy, 1 (8%). One patient (8%) had pulmonary wedge resections of bilateral pulmonary metastases. There was no perioperative mortality. Ten patients (83%) received additional chemotherapy. With a median follow-up of 25 months (range 8-94 months), the median survival time is 27 months. Three patients (25%) have no evidence of tumor recurrence at 8, 17, and 38 months of follow-up. Nine patients (75%) have had tumor recurrence at a median of 12 months from the time of surgery. CONCLUSIONS: Hepatic resection of metachronous metastases from gynecologic carcinomas can be performed safely and may help prolong survival in carefully selected patients.

Adult↗