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Yuman Fong

Publications and source records attributed to Yuman Fong.

105 records · Page 6Linked to original sources
PubMed2002

An audit of results of a no-drainage practice policy after hepatectomy.

BACKGROUND: It was hypothesized that routine operative drainage is unnecessary for elective hepatic resection. METHODS: A review was made of the clinical records of patients undergoing liver resection at a tertiary referral hepatobiliary surgery center since the conclusion in April of 1994 of our previous randomized drainage trial. The main outcome measures were operative drainage versus no operative drainage assessed for possible association with diagnoses, extent of hepatectomy, hospital course, and postoperative radiologic percutaneous drainage procedures. RESULTS: Of 1,165 patients, 184 were operatively drained with closed drains according to specific practice criteria and 981 were not subject to operative drainage. Patients who were not operatively drained had length of stay (10.1 days), mortality (2%), and complication rate (34%) comparable with the nondrained patients in the previous randomized trial. Ten percent of these patients required postoperative percutaneous drainage. Patients who were operatively drained were a group who were at higher risk for biliary leakage or infections and consequently had a significantly longer hospital stay, greater mortality, higher complication rate, and required a greater number of percutaneous abdominal drainages. CONCLUSIONS: The 84% of patients not operatively drained had no greater adverse outcome. After hepatic resection, routine drainage of the abdomen is unnecessary.

Adult↗
PubMed2002

Surgical indications and extent of resection in gallbladder cancer.

Gallbladder cancer often is diagnosed at an advanced stage when the prognosis is dismal. Early tumors (T1) that are recognized incidentally are curable with simple cholecystectomy alone. All other tumors should be resected with an extended cholecystectomy (T2) or with an extensive liver resection that obtains the negative margins. Patients with tumors greater than T1 should undergo lymphadenectomy that includes the porta hepatis and superior pancreatic nodes. Long-term survival with this approach is possible, even with T3 and T4 tumors. The role of extended lymphadenectomy, including the retropancreatic and aortocaval basins, is unclear and should be attempted only in selected cases.

Cholecystectomy, Laparoscopic↗
PubMed2002

Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer.

G207 and NV1020 are two replication-competent, multimutant oncolytic herpes simplex viruses evaluated in the current studies for their anticancer effects in the treatment of gastric cancer. Deletion of both gamma(1)34.5 genes and inactivation of ICP6 (ribonucleotide reductase) allows G207 to selectively replicate within tumor cells. NV1020 is another attenuated recombinant herpes virus with deletions of the HSV joint region, with deletion of only one copy of the gamma(1)34.5 gene, and with the ICP6 gene intact. In vitro, both G207 and NV1020 effectively infected, replicated, and killed human gastric cancer cells, with NV1020 being more effective at lower concentrations of virus. In a murine xenograft model of peritoneally disseminated gastric cancer, both NV1020 and G207 reduced tumor burden when given intraperitoneally (i.p.) at higher doses. When viral doses were lowered or when advanced tumor was treated, i.p. NV1020 was superior to i.p. G207. In vitro viral replication and cytotoxicity predicted the in vivo antitumor response. Intravenous delivery of either G207 or NV1020 failed to reduce tumor burden, demonstrating the importance of regional therapy as treatment for compartmentalized malignancy. Both agents were safe for use in animals, and immunohistochemistry performed on mouse tissue revealed selective viral targeting of tumor. Oncolytic therapy using genetically engineered HSVs represents a promising strategy for peritoneal malignancies.

Animals↗
PubMed2002

Ionizing radiation potentiates the antitumor efficacy of oncolytic herpes simplex virus G207 by upregulating ribonucleotide reductase.

BACKGROUND: Replication-competent herpes simplex virus-1 (HSV-1) mutants have an oncolytic effect on human and animal cancers. The aim of this study was to determine whether G207, an HSV-1 mutant, can be combined with ionizing radiation (IR) to increase antitumor activity while decreasing treatment-associated toxicity. METHODS: This study was performed by using G207, a replication-competent HSV-1 mutant deficient in viral ribonucleotide reductase (RR) and the gamma(1)34.5 neurovirulence protein. The antitumor activity of G207 or IR was tested against HCT-8 human colorectal cancer cells in vitro and in an in vivo mouse subcutaneous tumor model. RESULTS: We demonstrated that G207 has significant oncolytic effect on HCT-8 cells in vitro in a cytotoxicity assay and in vivo in a mouse flank tumor model and that these effects are improved with low-dose IR. We further illustrated that the increased tumoricidal effect is dependent on the up-regulation of cellular RR by IR measured by a functional bioassay for RR activity. Chemical inhibition of RR by hydroxyurea abrogates the enhanced effect. In contrast to G207, R3616, the parent virus of G207 that expresses functional RR, does not exhibit enhanced oncolysis when combined with IR. CONCLUSIONS: These data encourage clinical investigation of combination radiation therapy and HSV oncolytic therapy.

Animals↗
PubMed2002

Replication-competent herpes virus NV1020 as direct treatment of pleural cancer in a rat model.

OBJECTIVE: Innovative treatments are needed for metastatic disease involving the pleura. NV1020 is a novel, multimutated, replication-restricted herpes simplex virus under investigation for its ability to selectively kill tumors by means of direct cell lysis. This study examines NV1020 in a rat model of pleura-based lung cancer. METHODS: Cytotoxicity and viral proliferation were evaluated in vitro by exposure of the human non-small cell lung cancer cell line A549 to virus. NV1020 was also tested in an in vivo pleura-based cancer model established by injecting 1 x 10(7) A549 cells into the thoracic cavity of nude rats. Intrapleural treatments (1 x 10(7) viral particles) were given 3 hours or 3 days after tumor injection to model treatment of microscopic or macroscopic disease (n = 8-9/group). Tumor burden was assessed at 5 weeks. NV1020 infection and dissemination within the thoracic cavity was determined by means of immunohistochemistry. RESULTS: In vitro, at multiplicities of infection (viral particles per tumor cell) of 0.01, 0.1, and 1.0, cell killing of A549 by NV1020 was 66%, 90%, and 97%, respectively, at 7 days after infection. Viral burst occurred by day 2. Intrapleural treatment was effective for both the microscopic (P <.001) and macroscopic (P <.05) in vivo tumor models. Virus was detectable by means of immunohistochemistry in tumors but not in adjacent normal intrathoracic tissues. CONCLUSIONS: NV1020 is not only highly cytotoxic to the human lung cancer line A549 in vitro but can be delivered in a clinically relevant fashion to safely and effectively treat pleura-based tumor in vivo in a rat model.

Adenocarcinoma↗
PubMed2002

Staging laparoscopy in patients with extrahepatic biliary carcinoma. Analysis of 100 patients.

OBJECTIVE: To evaluate the benefit of staging laparoscopy in patients with gallbladder cancer and hilar cholangiocarcinoma. SUMMARY BACKGROUND DATA: In patients with extrahepatic biliary carcinoma, unresectable disease is often found at the time of exploration despite extensive preoperative evaluation, thus resulting in unnecessary laparotomy. METHODS: From October 1997 to May 2001, 100 patients with potentially resectable gallbladder cancer (n = 44) and hilar cholangiocarcinoma (n = 56) were prospectively evaluated. All patients underwent staging laparoscopy followed by laparotomy if the tumor appeared resectable. Surgical findings, resectability rate, length of stay, and operative time were analyzed. RESULTS: Patients underwent multiple preoperative imaging tests, including computed tomography scan, ultrasound, magnetic resonance cholangiopancreatography, and direct cholangiography. Laparoscopy identified unresectable disease in 35 of 100 patients. In the 65 patients undergoing open exploration, 34 were found to have unresectable disease. Therefore, the overall accuracy for detecting unresectable disease was 51%. There was no difference in the accuracy of laparoscopy between patients with gallbladder cancer and hilar cholangiocarcinoma. Laparoscopy detected the majority of patients with peritoneal or liver metastases but failed to detect all locally advanced tumors. In patients undergoing biopsy only, laparoscopic identification of unresectable disease significantly reduced operative time and length of stay compared with patients undergoing laparotomy. The yield of laparoscopy was 48% in patients with gallbladder cancer (56% in those who did not undergo previous cholecystectomy), but only 25% in patients with hilar cholangiocarcinoma. However, in patients with locally advanced but potentially resectable hilar cholangiocarcinoma, the yield of laparoscopy was greater, 36% (12/33, T2/T3 tumors) versus 9% (2/23, T1 tumors). CONCLUSIONS: Laparoscopy identifies the majority of patients with unresectable hilar cholangiocarcinoma or gallbladder carcinoma, thereby reducing both the incidence of unnecessary laparotomy and the length of stay. The yield of laparoscopy is lower for hilar cholangiocarcinoma but can be improved by targeting patients at higher risk of occult unresectable disease. All patients with potentially resectable primary gallbladder cancer and patients with T2/T3 hilar cholangiocarcinoma should undergo staging laparoscopy before surgical exploration.

Adult↗
PubMed2002

Second liver resections are safe and effective treatment for recurrent hepatic metastases from colorectal cancer: a bi-institutional analysis.

OBJECTIVE: To determine the value of repeat liver resection for recurrent colorectal metastases to the liver. SUMMARY BACKGROUND DATA: Liver resection represents the best and a potentially curative treatment for metastatic colorectal cancer to the liver. After resection, however, most patients develop recurrent disease, often isolated to the liver. METHODS: This study reports the combined experience of repeat liver resection for recurrent liver metastases at an American and a European surgical oncology center. Patients were identified from prospective databases and records were retrospectively reviewed. A total of 126 patients (American n = 96, 1986-2001; European n = 30, 1985-1999) underwent repeat liver resection. Patient characteristics were similar in the two institutions. Median follow-up from first liver resection was 88 and 105 months, respectively. RESULTS: Operations performed included 90 minor resections and 36 resections of a lobe or more. The 1-, 3-, and 5-year survival rates were 86%, 51%, and 34%. There were 19 actual 5-year survivors to date. By multivariate regression analysis (proportional hazard model), more than one lesion and tumor size larger than 5 cm were independent prognostic indicators of reduced survival. The interval between the first and second liver resection was not predictive of outcome. CONCLUSIONS: Repeat liver resection for colorectal liver metastases is safe. Patients with a low tumor load are the best candidates for a repeat resection. In well-selected patients, further resection of the liver can provide prolonged survival after recurrence of colorectal liver metastases.

Adult↗
PubMed2002

Efficacy of multiagent herpes simplex virus amplicon-mediated immunotherapy as adjuvant treatment for experimental hepatic cancer.

OBJECTIVE: To evaluate the use of herpes simplex viral (HSV) amplicon vectors for production of tumor vaccines and to determine if such vaccines expressing combinations of immunostimulatory agents may be effective in the treatment of experimental liver cancer. METHODS: A hepatic metastatic tumor model using CT-26 colorectal cancer in syngeneic Balb/C mice was utilized. Tumor vaccines were produced by brief (20 minutes) exposure of irradiated tumor cells to herpes amplicon vectors carrying the transgene for RANTES, B7.1, or GM-CSF. The antitumor efficacy of vaccination using tumor cells secreting GM-CSF (single agent) or a combination of RANTES/B7.1/GM-CSF (multiagent) was tested. The effect of 60% hepatectomy or T-cell depletion was also tested in this model. RESULTS: In vitro assays confirmed high-level cytokine or costimulatory molecule production by cells transduced with amplicons. Antitumor efficacy was observed with single-agent or multiagent treatment. Without hepatectomy, immunization with single-agent or multiagent vaccine therapy appears equivalent. When administered in the setting of hepatectomy, multiagent regimens produced a higher cure rate than single-agent therapy (50% vs. 12.5%, =.03). Animals treated with GM-CSF alone had an average nodule count of 40 +/- 19 ( <.006 vs. Hep control 232 +/- 30), while animals treated with multiagent therapy had an average nodule count of 11 +/- 7 ( <.0004 vs. control). CD4 and CD8 lymphocyte blockade abrogated observed efficacy, confirming a lymphocyte-mediated response. CONCLUSIONS: Tumor vaccines produced using HSV amplicon-mediated gene transfer may be useful in the treatment of liver malignancies. In the setting of hepatectomy, multiagent vaccine therapy offers an advantage over single-agent therapy. These data encourage consideration of such HSV-based neoadjuvant immunotherapy for treatment of liver malignancies.

Animals↗
PubMed2002

Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade.

OBJECTIVE: To assess the nature of changes in the field of hepatic resectional surgery and their impact on perioperative outcome. METHODS: Demographics, extent of resection, concomitant major procedures, operative and transfusion data, complications, and hospital stay were analyzed for 1,803 consecutive patients undergoing hepatic resection from December 1991 to September 2001 at Memorial Sloan-Kettering Cancer Center. Factors associated with morbidity and mortality and trends in operative and perioperative variables over the period of study were analyzed. RESULTS: Malignant disease was the most common diagnosis (1,642 patients, 91%); of these cases, metastatic colorectal cancer accounted for 62% (n = 1,021). Three hundred seventy-five resections (21%) were performed for primary hepatic or biliary cancers and 161 (9%) for benign disease. Anatomical resections were performed in 1,568 patients (87%) and included 544 extended hepatectomies, 483 hepatectomies, and 526 segmental resections. Sixty-two percent of patients had three or more segments resected, 42% had bilobar resections, and 37% had concomitant additional major procedures. The median blood loss was 600 mL and 49% of patients were transfused at any time during the index admission. Median hospital stay was 8 days, morbidity was 45%, and operative mortality was 3.1%. Over the study period, there was a significant increase in the use of parenchymal-sparing segmental resections and a decrease in the number of hepatic segments resected. In parallel with this, there was a significant decline in blood loss, the use of blood products, and hospital stay. Despite an increase in concomitant major procedures, operative mortality decreased from approximately 4% in the first 5 years of the study to 1.3% in the last 2 years, with 0 operative deaths in the last 184 consecutive cases. On multivariate analysis, the number of hepatic segments resected and operative blood loss were the only independent predictors of both perioperative morbidity and mortality. CONCLUSIONS: Over the past decade, the use of parenchymal-sparing segmental resections has increased significantly. The number of hepatic segments resected and operative blood loss were the only predictors of both perioperative morbidity and mortality, and reductions in both are largely responsible for the decrease in perioperative mortality, which has occurred despite an increase in concomitant major procedures.

Adolescent↗
PubMedDate not supplied

Use of positron emission tomography to target prostate cancer gene therapy by oncolytic herpes simplex virus.

Herpes simplex virus (HSV) oncolytic gene therapy is a promising treatment modality against cancer. We have demonstrated that androgen-induced cellular changes enhance oncolytic viral replication and improve efficacy in the treatment of androgen-dependent prostate cancer cell line. Imaging of changes in 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake by positron emission tomography (PET) is a sensitive method of detecting altered cellular metabolism involved in cancer therapy. We therefore hypothesized that FDG-PET can predict tumor response to oncolytic HSV therapy. In this study, androgen increased cell kill (74%) in vitro and enhanced viral yield (2.4-fold) in vivo following HSV therapy. This enhanced efficacy was predicted by high FDG accumulation in intact animals compared to low FDG uptake following orchiectomy (p = 0.002). This proof-of-concept study provides the mechanistic basis for selecting patients for targeted oncolytic viral therapy by means of a noninvasive molecular imaging method in the treatment of prostate cancer.

Animals↗
PubMedDate not supplied

Diabetes is associated with increased perioperative mortality but equivalent long-term outcome after hepatic resection for colorectal cancer.

Diabetes is associated with alterations in liver metabolism and immune response that may influence postoperative recovery and long-term survival after hepatectomy for cancer. Patients with type I or type II diabetes mellitus submitted to a potentially curative hepatic resection for metastatic colorectal cancer were identified from the prospective database, and compared with patients with hepatic colorectal metastases submitted to resection during the same time interval, but without diabetes mellitus. Data on operative morbidity and mortality and long-term survival were analyzed. Between December 1990 and July 1999, a total of 727 patients underwent hepatic resection, 61 of whom (8.1%) had type I and type II diabetes mellitus. Operative mortality in the diabetic patients was significantly greater than in nondiabetic patients (8% vs. 2%, P < 0.02). Among patients with diabetes mellitus, four of the five perioperative deaths were due to liver failure after major hepatic resection (lobectomy or greater). All four of these patients had significant parenchymal abnormality (three with steatosis). Long-term survival was identical to that in nondiabetic control subjects. We conclude that the presence of diabetes is associated with a higher incidence of perioperative mortality. In patients with diabetes mellitus and parenchymal steatosis, major hepatic resection should be undertaken with caution.

Adult↗
PubMedDate not supplied

Volumetric analysis predicts hepatic dysfunction in patients undergoing major liver resection.

Liver-enhancing modalities, such as portal vein embolization, are increasingly employed prior to major liver resection to prevent postoperative liver dysfunction. Selection criteria for such techniques are not well described. This study uses CT-based volumetric analysis as a tool to identify patients at highest risk for postoperative hepatic dysfunction. Between July 1999 and December 2000, a total of 126 consecutive patients who were undergoing liver resection for colorectal metastasis and had CT scans at our institution were included in the analysis. Volume of resection was determined by semiautomated contouring of the liver on preoperative volumetrically (helical) acquired CT scans. Hepatic dysfunction was defined as prothrombin time greater than 18 seconds or serum bilirubin level greater than 3 mg/dl. Marginal regression was used to compare the predictive ability of volumetric analysis and the extent of resection. The percentage of liver remaining was closely correlated with increasing prothrombin time and bilirubin level (P < 0.001). After trisegmentectomy, 90% of patients with </=25% of liver remaining developed hepatic dysfunction, compared with none of the patients with more than 25% of liver remaining after trisegmentectomy (P < 0.0001). The percentage of liver remaining was more specific in predicting hepatic dysfunction than was the anatomic extent of resection (P = 0.003). Male sex nearly doubled the risk of hepatic dysfunction (odds ratio = 1.89, P = 0.027), and having </=25% of liver remaining more than tripled the risk (odds ratio = 3.09, P < 0.0001). Hepatic dysfunction and </=25% of liver remaining were associated with increased complications and length of hospital stay (P < 0.0001 and P = 0.0003, respectively). Preoperative assessment of future liver volume remaining distinguishes which patients undergoing liver resection will most likely benefit from preoperative liver enhancement techniques such as portal vein embolization.

Adult↗
PubMedDate not supplied

Gallbladder carcinoma: findings at MR imaging with MR cholangiopancreatography.

PURPOSE: To describe magnetic resonance (MR) imaging and MR cholangiopancreatography (MRCP) findings in gallbladder carcinoma, and to correlate these findings with available surgical and biopsy information. METHODS: Preoperative MR images (T1-weighted spin-echo, T2-weighted fast spin-echo, single shot fast spin-echo, and dynamic gadolinium-enhanced gradient echo) in 34 patients with gallbladder carcinoma were retrospectively reviewed for appearance of the primary neoplasm and for demonstration of hepatic, peritoneal, duodenal, and nodal involvement. Imaging findings were then compared with surgical findings (n = 19 patients) and histologic findings (n = 15 patients). RESULTS: Gallbladder carcinoma manifested at MR imaging as focal gallbladder wall thickening with an eccentric mass in 76% (26/34) of cases. The most common types of regional spread demonstrated were direct liver invasion in 91% (31/34), lymphadenopathy in 76% (26/34), and biliary tract invasion in 62% (21/34). Sensitivity for direct hepatic invasion was 100%, and was 92% for lymph node metastasis. CONCLUSION: MRI and MRCP can provide information relevant to preoperative staging of gallbladder carcinoma.

Gallbladder↗
PubMedDate not supplied

Breath-hold magnetic resonance cholangiopancreatography in the evaluation of malignant pancreaticobiliary obstruction.

OBJECTIVE: This study was designed to determine the effectiveness of magnetic resonance cholangiopancreatography (MRCP) using a breath-hold single-shot fast spin echo (SSFSE) technique in imaging patients with malignant biliary and/or pancreatic duct obstruction. METHODS: One hundred thirty-one breath-hold MRCP studies in patients with malignant pancreatic and/or biliary obstruction were evaluated. Pathologic diagnoses included pancreatic cancer, biliary malignancy, gallbladder carcinoma, hepatic neoplasms, malignant lymphadenopathy, and ampullary carcinoma. Two observers independently reviewed the images in a blinded fashion to assess the level of obstruction and the site of underlying tumor. RESULTS: The level of obstruction was correctly identified in 104 of 131 cases (79%) by observer 1 and in 107 of 131 cases (82%) by observer 2. The site of underlying tumor was correctly identified in 113 of 131 cases (86%) by observer 1 and in 110 of 131 cases (84%) by observer 2. CONCLUSION: Magnetic resonance cholangiopancreatography utilizing the SSFSE technique can accurately assess the level of obstruction and the site of underlying tumor in patients with malignant pancreaticobiliary obstruction, without the risks of cholangiography. This MRCP technique allows for visualization of intra- and extraductal anatomy and pathology.

Bile Duct Neoplasms↗