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Yuman Fong

Publications and source records attributed to Yuman Fong.

At least 91 records · Page 5Linked to original sources
PubMed2003

Impact of steatosis on perioperative outcome following hepatic resection.

Fatty liver disease may interfere with liver regeneration and is postulated to result in an adverse outcome for patients subjected to partial hepatectomy. This study examines the impact of steatosis on outcome following hepatic resection for neoplasms. All patients with fatty livers (n=325) who underwent hepatectomy between December 1991 and September 2001 were identified from a prospective database. Slides were reviewed and steatosis was quantified as follows: <30% (mild) and > or =30% (marked). Patient data were gathered and compared with results in 160 control patients with normal livers; subjects were matched for age, comorbidity, and extent of liver resection. There were 223 patients with mild and 102 with marked steatosis. Those with steatosis were more likely to be men (59% marked vs. 55% mild vs. 43% control; P=0.01) with a higher body mass index (29.7+/-5.5 marked vs. 28.2+/-5.5 mild vs. 26.0+/-5.4 control; P<0.01), and treated preoperatively with chemotherapy (66% marked vs. 55% mild vs. 38% control; P<0.01). Total (62%, 48%, and 35%; P<0.01) and infective (43%, 24%, and 14%; P<0.01) complications correlated with the degree of steatosis. No difference was observed in complications requiring major medical intervention, hospitalization, or admission to the intensive care unit between groups. On multivariate analysis, steatosis was an independent predictor of complications (P<0.01, risk ratio=3.04, 95% confidence interval=1.7 to 5.54). There was a nonsignificant trend toward higher 60-day mortality in patients with marked steatosis who had lobe or more resections (9.4% marked vs. 5.0% mild vs. 5.0% control; P=0.30). Marked steatosis is an independent predictor of complications following hepatic resection but does not have a significant impact on 60-day mortality. Steatosis alone should not preclude aggressive hepatic resection for neoplasms when indicated; however, patients with marked steatosis undergoing large resections should still be approached with due caution.

Aged↗
PubMed2003

Predictors and patterns of recurrence after resection of hepatocellular carcinoma.

BACKGROUND: The majority of patients with hepatocellular carcinoma (HCC) who undergo complete tumor resection subsequently develop tumor recurrence. The objectives of this study were to determine the risk factors for recurrence of HCC after hepatectomy and to examine the outcomes once tumor recurrence occurs. STUDY DESIGN: From February 1990 to May 2001 a total of 164 patients underwent liver resection for HCC at our institution and were prospectively followed. Time to recurrence and survival after recurrence were determined by Kaplan-Meier analysis. Patient, tumor, and treatment characteristics were tested for their prognostic significance by univariate and multivariate analysis using the logrank test and the Cox proportional hazards model, respectively. RESULTS: The median patient age was 64 years (range 21 to 87 years) and 106 patients (65%) were male. After a median followup of 26 months, 90 patients (55%) have developed recurrent cancer. Among them, 75 patients (83%) had tumor detectable in the liver, which was the only site of disease in 67 (74%). In all, 15 patients (20%) had extrahepatic disease (7 lung, 4 peritoneum, 2 pancreas, 1 bone, and 1 brain). The median time to recurrence was 24 months (range 1 to 274 months). Predictors of recurrence on univariate analysis were tumor size greater than 5 cm, more than one tumor, cirrhosis, vascular invasion (microscopic or macroscopic), and tumor satellites. On multivariate analysis only tumor size greater than 5 cm (p = 0.04) and vascular invasion (p = 0.01) predicted recurrence. The median survival after recurrence was 11 months (range 0 to 60 months). Of the 90 patients who developed tumor recurrence 49 (67%) were able to undergo additional ablative or surgical therapy (33 embolization, 9 ethanol injection, and 14 re-resection). On multivariate analysis vascular invasion in the original tumor predicted poor survival after recurrence (p = 0.009). CONCLUSIONS: The liver is the predominant site of first recurrence after resection of hepatocellular carcinoma, and once recurrence occurs survival is limited. The current study underscores the need for effective adjuvant therapy for patients with HCC treated with partial hepatectomy.

Actuarial Analysis↗
PubMed2003

Resection of recurrent ovarian or fallopian tube carcinoma involving the liver.

OBJECTIVES: Patients who develop recurrent ovarian of fallopian tube carcinoma involving the liver often have disease refractory to chemotherapy and carry a poor prognosis. The impact of aggressive resection in this patient population is unclear. METHODS: From 1/1988 to 9/2001, 24 patients with recurrent ovarian or fallopian tube carcinoma who underwent complete gross resection or optimal debulking of their hepatic metastases and disease at other sites were identified from prospective databases at a single institution. RESULTS: The median age of patients was 53 years old, and the median interval between primary diagnosis and liver resection was 69 months. All patients had primary resection or cytoreduction and chemotherapy as part of their initial treatment. Subsequent hepatic resections included trisegmentectomy (2), lobectomy (2), segmentectomy (17), and wedge resection (3). Additional resection of disease outside the liver was performed in 18 patients (75%). Twenty-one patients (88%) had removal of all gross disease, and three patients (13%) had optimal tumor debulking to less than 1 cm. Eighteen patients recurred with sites of initial recurrence, including the abdomen and pelvis (14), spine/paraspinal region (2), lung (1), and liver (1). Overall median survival was 62 months after hepatic resection with a range of 6 to 94 months. Fourteen patients were alive at the time of last follow-up, and 10 had no evidence of disease. No significant prognostic factors for overall survival could be identified on univariate analysis. CONCLUSIONS: In highly selected patients with recurrent ovarian or fallopian tube carcinoma involving the liver, hepatic resection along with resection of other gross disease may lengthen survival and should be considered as a treatment option.

Adult↗
PubMed2003

The use of fresh frozen plasma after major hepatic resection for colorectal metastasis: is there a standard for transfusion?

BACKGROUND: Major hepatic resection is indicated for selected patients with colorectal metastasis to the liver. Transfusion of fresh frozen plasma (FFP) might be required after major hepatectomy because of blood loss or coagulopathy, but there are no standard criteria for the use of FFP in this setting. METHODS: We identified 260 patients from our prospective database who underwent major (> or =3 Couinaud segments) hepatectomy between May 1997 and February 2001 for colorectal metastasis. FFP use was determined and tested for its relationship to clinical and pathologic factors. A survey on FFP use was sent to 12 other hepatobiliary centers worldwide. RESULTS: There were 142 (55%) men, 118 (45%) women, and the median age was 63 years. The most common hepatic resections performed were right lobectomy (37%) and extended right lobectomy (33%). There were 83 (32%) patients who received FFP. In these patients, a total of 405 units of FFP were administered with a median of 4 units. The majority of patients who received FFP were transfused within the first two postoperative days, while there were only five (2%) patients who initially received FFP beyond that time. FFP was administered for a median prothrombin time of 16.9. Only one (0.4%) patient required reoperation for bleeding. Right lobectomy and extended right lobectomy were found to predict FFP use on multivariate analysis. Postoperative complications did not correlate with FFP use. The criteria used for FFP administration at other major hepatobiliary centers were found to be variable. CONCLUSIONS: There is no universal standard for FFP use following major hepatic resection for colorectal metastasis. Our criterion of a prothrombin time of 16-18 seconds is conservative but results only rarely in reoperation for bleeding. Prospective evaluation of a higher threshold for FFP administration, such as an International Normal Ratio of 2.0, should be performed to better define the guidelines for FFP use in patients undergoing major hepatectomy who have normal underlying hepatic parenchyma.

Blood Component Transfusion↗
PubMed2003

Simultaneous liver and colorectal resections are safe for synchronous colorectal liver metastasis.

BACKGROUND: The optimal surgical strategy for the treatment of synchronous resectable colorectal liver metastasis has not been defined. The aims of this study were to review our experience with synchronous colorectal metastasis and to define the safety of simultaneous versus staged resection of the colon and liver. STUDY DESIGN: From September 1984 through November 2001, 240 patients were treated surgically for primary adenocarcinoma of the large bowel and synchronous hepatic metastasis. Clinicopathologic, operative, and perioperative data were reviewed to evaluate selection criteria, operative methods, and perioperative outcomes. RESULTS: One hundred thirty-four patients underwent simultaneous resection of a colorectal primary and hepatic metastasis in a single operation (Group I), and 106 patients underwent staged operations (Group II). Simultaneous resections tend to be performed for right colon primaries (p < 0.001), smaller (p < 0.01) and fewer (p < 0.001) liver metastases, and less extensive liver resection (p < 0.001). Complications were less common in the simultaneous resection group, with 65 patients (49%) sustaining 142 complications, compared with 71 patients (67%) sustaining 197 complications for both hospitalizations in the staged resection group (p < 0.003). Patients having simultaneous resection required fewer days in the hospital (median 10 days versus 18 days, p = 0.001). Perioperative mortality was similar (simultaneous, n = 3; staged, n = 3). CONCLUSIONS: Simultaneous colon and liver resection is safe and efficient in the treatment of patients with colorectal cancer and synchronous liver metastasis. By avoiding a second laparotomy, the overall complication rate is reduced, with no change in operative mortality. Given its reduced morbidity, shorter treatment time, and similar cancer outcomes, simultaneous resection should be considered a safe option in patients with resectable synchronous colorectal metastasis.

Adenocarcinoma↗
PubMed2003

Diagnosis, management, and outcomes of 115 patients with hepatic hemangioma.

BACKGROUND: Hepatic hemangiomas are congenital vascular malformations and are the most common benign hepatic tumors. Because the use of cross-sectional imaging has increased, benign hepatic tumors, especially hemangiomas, are encountered more frequently, so clinicians should be familiar with the most appropriate diagnostic tests, management, and outcomes of patients with hepatic hemangioma. STUDY DESIGN: All patients with a primary diagnosis of hepatic hemangioma referred for surgical evaluation at our institution between January 1992 and December 2000 were identified from a prospective database. Demographics, presentation, tumor characteristics, diagnostic studies, surgical procedures, and outcomes were analyzed. RESULTS; Of 115 patients in the study, nearly half were asymptomatic. In symptomatic patients, abdominal pain or discomfort was the most common presenting symptom. At our institution, the diagnosis of hemangioma was established by ultrasonographic studies in 57% of patients tested, by CT scan in 73%, and by MRI in 84%. In patients with large tumors considered for resection, direct angiography or, more recently, CT angiography, confirmed the diagnosis in 27 of 29 patients (93%). Enucleation was performed in 31 (60%) of the 52 patients who underwent surgical resection; 63 patients were observed. Postoperative complications occurred in 13 patients (25%), and there were no perioperative deaths. Of the patients with symptoms before resection, 96% had resolution of symptoms after operation. CONCLUSIONS: Hepatic hemangioma can be diagnosed in most patients using noninvasive studies, particularly MRI. Hepatic hemangiomas can be removed safely if patients become symptomatic or when malignancy cannot be excluded. CT angiography can be a valuable preoperative study in patients with large tumors, and enucleation is the procedure of choice. In asymptomatic or minimally symptomatic patients, hepatic hemangiomas usually have a benign course and can be observed.

Adult↗
PubMed2003

Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases.

The purpose of this study was to compare the treatment and outcome in patients referred for staged resection of synchronous colorectal liver metastases. The records of patients who had undergone colon or rectal resection and were then referred for evaluation of clinically resectable synchronous liver metastases between January 1995 and January 2000 were reviewed. Comparisons were made between patients who did not receive neoadjuvant chemotherapy and had exploratory operations after recovery from colon resection and patients who did receive chemotherapy before liver resection. A total of 106 patients were treated during the 5-year period. Neoadjuvant chemotherapy was given to 52 of the patients; in 29 of them the disease did not progress, but in 17 patients the disease progressed while they were receiving treatment. Median follow-up was 30 months. Patient- and tumor-related variables were similar between groups. Five-year survival was statistically similar between patients who did and those who did not receive neoadjuvant chemotherapy (43% vs. 35%, P = 0.49). Patients within the neoadjuvant group whose disease did not progress while they were receiving chemotherapy experienced significantly improved survival as compared to patients who did not receive chemotherapy (85% vs. 35%, P = 0.03). In the setting of synchronous colorectal liver metastases, the response to neoadjuvant chemotherapy may be a prognostic indicator of survival and may assist in the selection of patients for conventional or experimental adjuvant therapies.

Antineoplastic Agents↗
PubMed2003

The replication-competent oncolytic herpes simplex mutant virus NV1066 is effective in the treatment of esophageal cancer.

BACKGROUND: The oncolytic herpes simplex-1 virus, NV1066, is a replication-competent virus that has been engineered to infect and lyse tumor cells selectively and to carry a transgene for enhanced green fluorescent protein (EGFP). The purpose of this study was to determine viral cytotoxicity in an esophageal cancer cell line and to determine whether EGFP expression could be used as a marker of viral infection. METHODS: BE3 esophageal adenocarcinoma cells were infected with NV1066 in vitro to determine cell kill and viral replication. EGFP expression was assessed by flow cytometry. The in vivo anti-tumor activity of NV1066 was tested in subcutaneous and intraperitoneal xenograft models. EGFP expression was localized in vivo by fluorescent microscopy and fluorescent laparoscopy. RESULTS: NV1066 effectively replicated within and killed BE3 cells in vitro and in vivo. EGFP expression identified infected tumor cells. After NV1066 treatment in vivo, EGFP expression localized to the tumor. In an intraperitoneal tumor model, EGFP could be visualized endoscopically using a laparoscope with a fluorescent filter. CONCLUSIONS: NV1066 has oncolytic activity against the BE3 cell line and may be a useful therapy against esophageal cancer. EGFP expression localizes the virus and may help to identify tumor deposits in vivo. Oncolytic activity with NV1066 against gastrointestinal cancers may potentially be tracked by endoscopy.

Adenocarcinoma↗
PubMed2003

Influence of transfusions on perioperative and long-term outcome in patients following hepatic resection for colorectal metastases.

OBJECTIVE: To determine if transfusion affected perioperative and long-term outcome in patients undergoing liver resection for metastatic colorectal cancer. SUMMARY BACKGROUND DATA: Blood transfusion produces host immunosuppression and has been postulated to result in adverse outcome for patients undergoing surgical resection of malignancies. METHODS: Blood transfusion records and clinical outcomes for 1,351 patients undergoing liver resection at a tertiary cancer referral center were analyzed. RESULTS: Blood transfusion was associated with adverse outcome after liver resection. The greatest effect was in the perioperative course, where transfusion was an independent predictor of operative mortality, complications, major complications, and length of hospital stay. This effect was dose-related. Patients receiving one or two units or more than two units had an operative mortality of 2.5% and 11.1%, respectively, compared to 1.2% for patients not requiring transfusions. Transfusion was also associated with adverse long-term survival by univariate analysis, but this factor was not significant on multivariate analysis. Even patients receiving only one or two units had a more adverse outcome. CONCLUSIONS: Perioperative blood transfusion is a risk factor for poor outcome after liver resection. Blood conservation methods should be used to avoid transfusion, especially in patents currently requiring limited amounts of transfused blood products.

Blood Transfusion↗
PubMed2003

Resection of hepatocellular carcinoma in patients otherwise eligible for transplantation.

INTRODUCTION: The incidence of hepatocellular carcinoma (HCC) in the United States has increased 75% in the last decade. Liver transplantation is gaining acceptance for the treatment of early HCC, even in patients with adequate liver function. The objective of this study was to determine the long-term outcome of patients with early HCC who would have been candidates for transplantation but were treated instead with partial hepatectomy. METHODS: From August 1989 to November 2001, 611 patients with HCC were evaluated at our institution and entered into a prospective database. There were 180 (29%) patients who underwent partial hepatectomy, of whom 36 (20%) satisfied the currently accepted criteria for transplantation: 2 or 3 lesions each </= 3 cm in size or a solitary tumor </= 5 cm. Survival was determined by Kaplan-Meier analysis. RESULTS: Median tumor size was 3.5 (range, 1.8-5) cm and the median number of lesions was 1 (range, 1-3). Patients had pathologically confirmed cirrhosis of the liver in 78% (28/36) of cases, and 86% had normal liver function (Child class A). Perioperative morbidity was 25%, the median length of hospital stay was 8 (range, 4-24) days, and there was 1 (2.8%) perioperative death. At a median follow-up of 35 months for survivors, the 1-, 3-, and 5-year overall survival was 85%, 74%, and 69%, respectively, with a median survival of 71 months. The 5-year disease-free survival was 48% with a median of 52 months. CONCLUSIONS: Partial hepatectomy in patients with early HCC who are otherwise eligible for transplantation can be performed with minimal morbidity and can achieve comparable 5-year survival to that reported for liver transplantation. Resection should be considered the standard therapy for patients with HCC who have adequate liver reserve.

Aged↗
PubMed2002

Oncolytic viral gene therapy for prostate cancer using two attenuated, replication-competent, genetically engineered herpes simplex viruses.

BACKGROUND: Attenuated, replication-competent herpes simplex virus mutants offer an exciting new modality in cancer therapy through their ability to selectively replicate within and kill malignant cells with minimal harm to normal tissues. METHODS: This study investigates the efficacy of two such viruses, G207 and NV1020, in human prostatic carcinoma. In vitro studies were performed on four human prostatic carcinoma cell lines, and in vivo single/multiple dose studies were undertaken on mice by using two human cell types. Tumor volume, histopathology at necropsy, and serum prostate specific antigen (PSA) were used as measures of antiproliferative effect in the in vivo experiments. RESULTS: Both viruses were effective in producing cytolytic effects in vitro at various multiplicities of infection in all cell lines tested. Both viruses demonstrated antitumor effects in vivo with a statistically significant decrease in serum PSA and inhibition of growth of both PC-3 and C4-2 subcutaneous xenografts. Tumor-free animals at necropsy were observed in the treated groups but not in control animals. CONCLUSION: These results display impressive activity against human prostate cancer and offer promise for the use of this modality in the future.

Animals↗
PubMed2002

Oncolytic herpesvirus effectively treats murine squamous cell carcinoma and spreads by natural lymphatics to treat sites of lymphatic metastases.

Oncolytic herpesviruses have significant antitumoral effects in animal models when delivered directly to established tumors. Lymphatic metastases are a common occurrence for many tumor types. This study investigates the potential of an attenuated, replication-competent, oncolytic herpes simplex virus (NV1023) both to treat a primary tumor by direct injection and to travel through the lymphatic system to treat metastatic tumor within the lymph nodes draining lymph from the site of primary cancer. Isosulfan blue dye was injected into murine auricles to determine normal lymphatic drainage patterns and demonstrated consistent blue staining of a group of ipsilateral cervical lymph nodes. Auricular injections of NV1023 resulted in viral transit to these lymph nodes as measured by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside histochemistry and viral plaque assay. An oncolytic herpesvirus (NV1066) expressing green fluorescent protein also demonstrated viral transit from the auricle to the cervical lymph nodes on fluorescence microscopy. Using the SCC VII cell line, a novel murine model of auricular squamous cell carcinoma was developed with an approximately 20% incidence of cervical lymph node metastases. Delivery of NV1023 or NV1066 to the surgical beds after excision of auricular SCC VII tumors resulted in successful viral infection of metastatic SCC VII cells within the cervical lymph nodes. After a 7-week follow-up, significantly enhanced locoregional control (p < 0.05, Fisher exact test) and disease-free survival (p < 0.05, log rank test) were evident with NV1023 treatment. This study demonstrates that the delivery of an oncolytic herpesvirus to a primary tumor site after surgical excision may have a significant impact on reducing both primary site recurrence and regional nodal metastases.

Animals↗
PubMed2002

Measuring health-related quality of life in patients with hepatobiliary cancers: the functional assessment of cancer therapy-hepatobiliary questionnaire.

PURPOSE: This is the first report on the development and initial validation of the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire, a 45-item self-report instrument designed to measure health-related quality of life (HRQL) in patients with hepatobiliary cancers. The FACT-Hep consists of the 27-item FACT-G, which assesses generic HRQL concerns, and the newly validated 18-item Hepatobiliary Subscale (HS), which assesses disease-specific issues. PATIENTS AND METHODS: The development of the HS followed a four-phase process of item generation, item reduction, scale construction, and reliability/validity testing. Two independent samples were studied: item generation (sample 1; n = 30) and reliability/validity testing (sample 2; n = 51). RESULTS: In sample 2, all subscales and aggregated scores showed high internal consistency at initial assessment (Cronbach's alpha range, 0.72 to 0.94) and retesting (Cronbach's alpha range, 0.81 to 0.94). Measurement stability over a 3- to 7-day period was also high for all aggregated scales (test-retest correlation range, 0.84 to 0.91; intraclass correlation coefficient range, 0.82 to 0.90). Convergent and divergent validity were demonstrated by examining relationships between FACT subscales and mood, social support, and social desirability. Finally, when performance status and treatment status were used to divide sample 2, the HS differentiated groups to a degree comparable to the Physical and Functional Well-Being subscales of the FACT-G, thereby contributing favorably to a 32-item Trial Outcome Index. In addition to the 18 validated, scored items in the HS, seven treatment-related items may be appended, if clinically indicated, as a separate subscale. CONCLUSION: The 45-item FACT-Hep can be used independently as a brief measure of disease-related symptoms and functioning. Alone or paired with the FACT-G, the HS has promise for use in assessing the disease-specific HRQL of patients with hepatobiliary cancers.

Adult↗
PubMed2002

Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors.

BACKGROUND: Tumors with combined hepatocellular and cholangiocellular features are well known histopathologically but their clinical behavior is poorly understood. The objectives of the current study were to define the demographic profile of the patients in whom these uncommon tumors occur and to evaluate treatment outcome in comparison with that in patients with either hepatocellular carcinoma (HCC) or peripheral cholangiocarcinoma (CC) alone. METHODS: Twenty-seven patients with combined tumors were identified from a prospective database. Pathologic specimens were analyzed to confirm the diagnosis. Demographics, clinical data, and survival were analyzed. Outcome after resection was compared with that of patients with CC and with a matched group of patients with HCC. RESULTS: The gender distribution of the combined tumors (52% men and 48% women) was intermediate between HCC (67% men and 33% women) and CC (30% men and 70% women) (P = 0.03). The incidence of positive hepatitis B or C serology and cirrhosis was similar in patients with combined tumors and those with CC (15% and 0% vs. 13% and 4%, respectively); similarly, patients of Asian heritage constituted 7% and 9%, respectively, of the patients with these tumors. By contrast, cirrhosis (41%) and positive hepatitis serology (56%) were far more common in patients with HCC, and 19% of these patients were of Asian heritage. Twenty-one of 27 patients with combined tumors (78%) underwent resection. All 6 patients with combined tumors that were not amenable to resection died of disease within 18 months. After resection, the 5-year survival was lowest in patients with combined tumors (24%) but was not significantly different from that in patients with CC (33%) or HCC (37%). The liver was the most common site of recurrence in all three groups. CONCLUSIONS: The demographic and clinical features of patients with combined tumors were most similar to those of patients with CC. Most important, combined tumors were not found to be associated with chronic liver disease; consequently, the resectability rate was higher for these tumors than typically is reported for HCC. Resection was associated with long-term survival in some patients, but recurrent hepatic disease was common. The presence of cholangiocellular differentiation appeared to worsen the prognosis when compared with pure HCC, although this difference did not reach statistical significance.

Adult↗
PubMed2002

Cells exposed to antifolates show increased cellular levels of proteins fused to dihydrofolate reductase: a method to modulate gene expression.

Human cells exposed to antifolates show a rapid increase in the levels of the enzyme dihydrofolate reductase (DHFR). We hypothesized that this adaptive response mechanism can be used to elevate cellular levels of proteins fused to DHFR. In this study, mouse cells transfected to express a green fluorescent protein-DHFR fusion protein and subsequently exposed to the antifolate trimetrexate (TMTX) showed a specific and time-dependent increase in cellular levels of the fusion protein. Next, human HCT-8 and HCT-116 colon cancer cells retrovirally transduced to express a DHFR-herpes simplex virus 1 thymidine kinase (HSV1 TK) fusion protein and treated with the DHFR inhibitor TMTX exhibited increased levels of the DHFR-HSV1 TK fusion protein and an increase in ganciclovir sensitivity by 250-fold. The level of fusion protein in antifolate-treated human tumor cells was increased in response to a 24-h exposure of methotrexate, trimetrexate, as well as dihydrofolate. This effect depended on the antifolate concentration and was independent of the fusion-protein mRNA levels, consistent with this increase occurring at a translational level. In a xenograft model, nude rats bearing DHFR-HSV1 TK-transduced HCT-8 tumors and treated with TMTX showed, after 24 h, a 2- to 4-fold increase of fusion-protein levels in tumor tissue from treated animals compared with controls, as determined by Western blotting. The fusion-protein increase was imaged with positron-emission tomography, where a substantially enhanced signal of the transduced tumor was detected in animals after antifolate administration. Drug-mediated elevation of cellular DHFR-fused proteins is a very useful method to modulate gene expression in vivo for imaging as well as therapeutic purposes.

Animals↗
PubMed2002

Molecular therapies for colorectal cancer metastatic to the liver.

Colorectal cancers are the fourth most commonly diagnosed cancers and will account for over 56,000 deaths in the United States in 2002. A majority of patients with advanced colorectal cancer develop liver metastases during the course of their disease. Treatment of colorectal cancer metastatic to the liver by surgery or chemotherapy is limited and most patients succumb to their disease. Therefore, a broad spectrum of novel treatments, including innovative molecular therapies such as gene and immunotherapy or replication-competent viral therapy, is under preclinical investigation and several clinical trials are in progress. Here we review molecular therapies for colorectal cancer metastatic to the liver.

Animals↗
PubMed2002

The management of variant arterial anatomy during hepatic arterial infusion pump placement.

BACKGROUND: The success of hepatic arterial infusion pump (HAIP) placement in patients with variant arterial anatomy has not been well described. METHODS: Patients who underwent HAIP placement over a 5-year time period were evaluated. Arterial- and catheter-related pump complication rates and pump survival were compared between patients with normal and variant arterial anatomy. RESULTS: Pumps were placed in 265 patients. Variant anatomy was present in 98 (37%) patients. The presence of variant versus normal anatomy did not increase pump complication rates (8% vs. 4%; P =.18) or decrease pump survival (P =.12). In all patients with an isolated variant right or left hepatic artery (n = 56), ligation of the variant vessel and cannulation of the gastroduodenal artery (GDA) resulted in complete hepatic perfusion and no pump complications. Cannulation of vessels other than the GDA (n = 22) was associated with increased pump complication rates (27% vs. 4%; P =.0001) and decreased pump survival (P =.002). CONCLUSIONS: In this study, HAIP placement in patients with variant anatomy was not associated with increased pump complication rates or decreased pump survival. An optimal strategy for managing variant anatomy is to ligate isolated variant vessels and cannulate the GDA.

Catheterization, Peripheral↗