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Y Fong

Publications and source records attributed to Y Fong.

At least 55 records · Page 3Linked to original sources
PubMed2000

Natural ceramide reverses Fas resistance of acid sphingomyelinase(-/-) hepatocytes.

The role of the second messenger ceramide in Fas-mediated death requires clarification. To address this issue, we generated hepatocytes from paired acid sphingomyelinase (ASMase; asmase)(+/+) and asmase(-/-) mice. asmase(-/-) hepatocytes, derived from 8-week-old mice, manifested normal sphingomyelin content and normal morphological, biochemical, and biologic features. Nonetheless, ASMase-deficient hepatocytes did not display rapid ceramide elevation or apoptosis in response to Jo2 anti-Fas antibody. asmase(-/-) hepatocytes were not inherently resistant to apoptosis because staurosporine, which did not induce early ceramide elevation, stimulated a normal apoptotic response. The addition of low nanomolar quantities of natural C16-ceramide, which by itself did not induce apoptosis, completely restored the apoptotic response to anti-Fas in asmase(-/-) hepatocytes. Other sphingolipids did not replace natural ceramide and restore Fas sensitivity. Overcoming resistance to Fas in asmase(-/-) hepatocytes by natural ceramide is evidence that it is the lack of ceramide and not ASMase which determines the apoptotic phenotype. The ability of natural ceramide to rescue the phenotype without reversing the genotype provides evidence that ceramide is obligate for Fas induction of apoptosis in hepatocytes.

Animals↗
PubMed2000

Use of phosphorous-31 nuclear magnetic resonance spectroscopy to determine safe timing of chemotherapy after hepatic resection.

Liver resection induces accelerated growth of residual hepatic micrometastases. Adjuvant chemotherapy may improve outcome if administered early after resection but may prove lethal if initiated prior to completion of DNA synthesis in regenerating liver. This study investigates phosphorus-31 nuclear magnetic resonance ((31)P-NMR) as a noninvasive tool for measuring energy changes reflective of hepatic DNA synthesis and for predicting safe timing of chemotherapy after 70% hepatectomy. To evaluate metabolic changes in regenerating liver, quantitative three-dimensional (31)P-NMR was performed, using the technique of chemical shift imaging at various time points after 70% hepatectomy in adult male Fischer rats. Animals receiving a course of 2'-deoxy-5-fluorouridine (FUDR; 100 mg/kg, i.p. four times per day x 5), initiated at the time of operation, were also evaluated to observe the effects of chemotherapy on liver regeneration. Forty-eight hours after resection, hepatic nucleoside triphosphate (NTP), which reflects ATP content, fell 37% (P < 0.03) in animals undergoing hepatectomy alone. By contrast, animals receiving FUDR after hepatectomy demonstrated a mitigated NTP response, with a drop of only 17% (P = not significant), suggesting that interruption of DNA synthesis leads to a reduced consumption of ATP. Direct measures of DNA synthesis and nuclear proliferation were correlated with NMR findings. [(3)H]Thymidine incorporation and Ki67 immunohistochemistry were performed on liver samples from rats undergoing 70% hepatectomy with and without FUDR. Both [(3)H]thymidine incorporation and Ki67 expression were inhibited significantly at 48 h in animals receiving hepatectomy and FUDR, compared with those not treated with FUDR. To determine whether NMR changes could be used to identify safe timing of chemotherapy after hepatectomy, rats were treated with a 5-day course of FUDR initiated either prior to or after NMR changes normalized. Animals treated with FUDR at the point of NTP normalization (72 h) showed significantly improved survival over those that began treatment at operation (75 % versus 17 %; P = 0.0005, log rank test). FUDR inhibits hepatic DNA synthesis and influences mortality if administered too early after hepatectomy. Chemical shift imaging is a noninvasive tool that can identify metabolic changes coinciding with DNA synthesis and nuclear proliferation after hepatectomy. (31)P-NMR may be useful for determining safe timing of chemotherapy after liver resection.

Animals↗
PubMed2000

Levels of E2F-1 expression are higher in lung metastasis of colon cancer as compared with hepatic metastasis and correlate with levels of thymidylate synthase.

We recently reported that forced overexpression of the transcription factor E2F-1 in human HT-1080 fibrosarcoma cells resulted in corresponding high levels of thymidylate synthase (TS) and resistance to 5-fluoropyrimidines (D. Banerjee et al., Cancer Res., 58: 4292-4296, 1998). Because colorectal metastasis to the lung has higher TS levels than liver metastasis and is less responsive to treatment with 5-fluorouracil (R. Gorlick et al., J. Clin. Oncol., 16: 1465-1469, 1998), it was, therefore, of interest to measure E2F-1 expression in these tumors. In contrast to marginally increased levels of dihydrofolate reductase and topoisomerase I in lung metastasis as compared with liver metastasis, lung tumors had a 5-fold increase in E2F-1 expression as compared with liver tumors, corresponding to the relative levels of TS in these metastases. These data indicate that there exists a close correlation between E2F-1 and TS levels and provide a rationale for targeting this transcription factor, ie., E2F-1, for the treatment of certain cancers.

Adenocarcinoma↗
PubMed2000

Requirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated tat stimulation of HIV-1 transcription.

Tat activation of HIV-1 transcription is mediated by human transcription elongation factor P-TEFb, which interacts with Tat and phosphorylates the C-terminal domain of RNA polymerase II. The catalytic subunit of the P-TEFb complex, Cdk9, has been shown to interact with cyclin T and several other proteins of unknown identity. Consequently, the exact subunit composition of active P-TEFb has not been determined. Here we report the affinity purification and identification of the Cdk9-associated proteins. In addition to forming a heterodimer with cyclin T1, Cdk9 interacted with the molecular chaperone Hsp70 or a kinase-specific chaperone complex, Hsp90/Cdc37, to form two separate chaperone-Cdk9 complexes. Although the Cdk9/cyclin T1 dimer was exceptionally stable and produced slowly in the cell, free and unprotected Cdk9 appeared to be degraded rapidly. Several lines of evidence indicate the heterodimer of Cdk9/cyclin T1 to be the mature, active form of P-TEFb responsible for phosphorylation of the C-terminal domain of RNA polymerase II interaction with the Tat activation domain, and mediation of Tat activation of HIV-1 transcription. Pharmacological inactivation of Hsp90/Cdc37 function by geldanamycin revealed an essential role for the chaperone-Cdk9 complexes in generation of Cdk9/cyclin T1. Our data suggest a previously unrecognized chaperone-dependent pathway involving the sequential actions of Hsp70 and Hsp90/Cdc37 in the stabilization/folding of Cdk9 as well as the assembly of an active Cdk9/cyclin T1 complex responsible for P-TEFb-mediated Tat transactivation.

Benzoquinones↗
PubMed2000

Hand-assisted laparoscopic liver resection: lessons from an initial experience.

BACKGROUND: Recent innovations in laparoscopic instrumentation make routine resection of solid organs a clinical possibility. HYPOTHESIS: Hand-assisted laparoscopic liver resection is a safe and feasible procedure for solitary cancers requiring removal of 2 segments of liver or less. DESIGN AND PATIENTS: Eleven patients with liver tumors deemed technically resectable by laparoscopic techniques were subjected to laparoscopic evaluation and attempted hand-assisted laparoscopic resection between July 1998 and July 1999. During the same period, 230 patients underwent open liver resection. SETTING: Tertiary care referral center for liver cancer. MAIN OUTCOME MEASURES: Success of laparoscopic resection, reasons for conversion to open liver resection, blood loss, tumor clearance margin, complications, and length of hospital stay. RESULTS: Five patients underwent successful resection by the hand-assisted laparoscopic technique. Data from the 5 successful cases and the 6 aborted cases are presented to outline the issues and the lessons learned. CONCLUSIONS: In selected patients, hand-assisted laparoscopic liver resection can be safely performed and might have potential advantages over traditional liver resection if the tumor is limited to the left lateral segment or is at the margins of the liver.

Adult↗
PubMed2000

Antitumor efficacy of regional oncolytic viral therapy for peritoneally disseminated cancer.

Oncolytic viral therapy is a promising new method of cancer treatment. Peritoneal dissemination of cancer is a common and fatal clinical condition seen in many malignancies, with few effective therapies available. G207, a multimutated replication-competent herpes simplex virus type-1, effectively treats disseminated peritoneal cancer. This study evaluates viral proliferation and subsequent tumoricidal effects in vitro and in vivo after regional viral delivery. In vitro studies demonstrate that G207 efficiently kills five human gastric cancer cell lines, and that permissiveness to viral replication is correlated with cytotoxicity. In a murine xenograft model of human gastric carcinomatosis, peritoneal delivery of G207 effectively kills tumor and prolongs survival. Data from quantitative PCR characterizes peritoneal clearance of virus after intraperitoneal injection, and identifies G207 replication within tumor cells in vivo, similar to in vitro proliferation. Further analysis of various organs confirms that G207 does not replicate within normal tissue after peritoneal delivery. Wild-type KOS viral replication was also demonstrated in vivo, with significant toxicity secondary to dissemination and encephalitis. In vivo viral proliferation of G207 is restricted to tumor cells, is correlated with in vitro assays, and is an important mechanism of anticancer efficacy.

Animals↗
PubMed2000

Survival after resection of multiple hepatic colorectal metastases.

BACKGROUND: Hepatic resection is potentially curative in selected patients with colorectal metastases. It is a widely held practice that multiple colorectal hepatic metastases are not resected, although outcome after removal of four or more metastases is not well defined. METHODS: Patients with four or more colorectal hepatic metastases who submitted to resection were identified from a prospective database. Number of metastases was determined by serial sectioning of the gross specimen at the time of resection. Demographic data, tumor characteristics, complications, and survival were analyzed. RESULTS: From August 1985 to September 1998, 155 patients with four or more metastatic tumors (range 4-20) underwent potentially curative resection by extended hepatectomy (39%), lobectomy (42%), or multiple segmental resections (19%). Operative morbidity and mortality were 26% and 1%, respectively. Actuarial 5-year survival was 23% for the entire group (median = 32 months) and there were 12 actual 5-year survivors. On multivariate analysis, only number of hepatic tumors (P = .005) and the presence of a positive margin (P = .003) were independent predictors of poor survival. CONCLUSIONS: Hepatic resection in patients with four or more colorectal metastases can achieve long-term survival although the results are less favorable as the number of tumors increases. Number of hepatic metastases alone should not be used as a sole contraindication to resection, but it is clear that the majority of patients will not be cured after resection of multiple lesions.

Adult↗
PubMed2000

The effectiveness of a topical antibiotic irrigating solution in a model of staphylococcal keratitis after lamellar keratectomy.

PURPOSE: To create a model of Staphylococcus aureus keratitis after lamellar keratectomy; to assess the toxicity of an antibiotic irrigating solution on the corneal stromal bed; and to test the chemotherapeutic effectiveness of a topical antibiotic, both alone and with an antibiotic-containing irrigating solution in preventing S. aureus keratitis after lamellar keratectomy. METHODS: The right eye of each of 38 rabbits were used in this study. In 18 eyes, a lamellar flap was created with a microkeratome, and an inoculum of S. aureus (either 1,000, 5,000, or 50,000 CFUs) was instilled under each flap; the eyes were examined for signs of infection and inflammation at 24 and 48 hours. In another five eyes, a lamellar flap was created in the same manner and the stromal bed was irrigated with 0.3% ofloxacin; the eyes were assessed for ocular inflammatory changes and evidence of crystalline deposits. Finally, in each of 15 additional eyes, 1,000 CFUs of S. aureus were instilled under a lamellar flap to create experimental infectious keratitis. The keratitis was treated according to three regimens: irrigation of the stromal bed with sterile balanced salt solution; irrigation of the stromal bed with 0.3% ofloxacin, followed by application of topical ofloxacin four times a day; application of topical ofloxacin only, four times a day. Eyes were examined for infection and ocular inflammatory changes at 24 and 48 hours. RESULTS: Staphylococcus aureus keratitis can consistently be produced under the stromal flap by inoculation of relatively few organisms. Irrigation of the stromal bed with commercial-strength topical ofloxacin does not appear to be toxic to the stromal bed, with no evidence of crystalline precipitates of the antibiotic. In our model of infectious keratitis after lamellar keratectomy, both topical ofloxacin alone and the combination of topical ofloxacin and irrigation of the stromal bed with 0.3% ofloxacin were effective at preventing S. aureus keratitis. However, the combined treatment of antibiotic irrigation plus topical antibiotic was more effective at preventing inflammation than topical ofloxacin alone. CONCLUSIONS: In this model of S. aureus keratitis after lamellar keratectomy, irrigation of the stromal bed with antibiotic plus topical antibiotic appears to be both safe and effective for preventing infection.

Administration, Topical↗
PubMed2000

A quantitative assessment of liver metabolites during jaundice using three dimensional phosphorus chemical shift imaging.

Phosphorus metabolites in the jaundiced rat liver were studied by three-dimensional phosphorus chemical shift imaging (CSI). Animals were studied at 1, 2, and 3 weeks post-ligation of the common bile duct. Quantitation of metabolites was performed using an external standard. Metabolite T(1) values were assessed in CSI experiments on normal untreated animals. High-performance liquid chromatography (HPLC) was used to measure adenine nucleotides in a separate group of jaundiced rats. 3D-CSI did not detect significant changes in NTP in jaundiced animals relative to baseline controls. At two and three weeks post bile duct ligation, pH was significantly elevated. HPLC data comparing ATP levels to baseline controls also detected no change except for elevated ATP detected on Day 21. (31)P NMR chemical shift imaging may be used to assess liver metabolites under conditions of stress such as jaundice. However, absolute quantitation requires careful attention to many factors including point spread function, correct T(1) values, and adequate signal-to-noise ratio.

Adenosine Triphosphate↗
PubMed2000

Hepatic neuroendocrine metastases: does intervention alter outcomes?

BACKGROUND: In most instances, advanced neuroendocrine tumors follow an indolent course. Hepatic metastases are common, and although they can cause significant pain, incapacitating endocrinopathy, and even death, they are usually asymptomatic. The appropriate timing and efficacy of interventions, such as hepatic artery embolization (HAE) and operation, remain controversial. STUDY DESIGN: The records of 85 selected patients referred for treatment of hepatic neuroendocrine tumor metastases between 1992 and 1998 were reviewed from a prospective database. A multidisciplinary group of surgeons, radiologists, and oncologists managed all patients. Overall survival among this cohort is reported and prognostic variables, which may be predictive of survival, are analyzed. RESULTS: There were 37 men and 48 women, with a median age of 52 years. There were 41 carcinoid tumors, 26 nonfunctional islet cell tumors, and 18 functional islet cell tumors. Thirty-eight patients had extrahepatic metastases, and in 84% of patients, the liver metastases were bilobar. Eighteen patients were treated with medical therapy or best supportive care, 33 patients underwent HAE, and 34 patients underwent hepatic resection. Both the HAE-related mortality and the 30-day operative mortality rates were 6%. By univariate analysis, earlier resection of the primary tumor, curative intent of treatment, and initial surgical treatment were associated with prolonged survival (p < 0.05). On multivariate analysis, only curative intent to treat remained significant (p < 0.04). Patients with bilobar or more than 75% liver involvement by tumor were least likely to benefit from surgical resection. One-, 3-, and 5-year survival rates for the entire group were 83%, 61%, and 53%, respectively. The 1-, 3-, and 5-year survivals for patients treated with medical therapy, HAE, and operation were 76%, 39%, and not available; 94%, 83%, and 50%; and 94%, 83%, and 76%, respectively. CONCLUSIONS: Hepatic metastases from neuroendocrine tumors are best managed with a multidisciplinary approach. Both HAE and surgical resection provide excellent palliation of hormonal and pain symptoms. In select patients, surgical resection of hepatic metastases may prolong survival, but is rarely curative.

Adult↗
PubMed2000

Whole-Body FDG-PET in Patients with Recurrent Colorectal Carcinoma. A Comparative Study with CT.

Purpose: To assess the clinical accuracy of whole-body 2-[F-18]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in the diagnosis of recurrent colorectal carcinoma in comparison to conventional computed tomography (CT).Materials and methods: Forty patients with suspected recurrent colorectal carcinoma based on either progressive serial carcinoemrbyonic antigen (CEA) serum elevation or positive/equivocal CT findings underwent whole-body FDG-PET. PET results were compared with those of CT and correlated to the final histopathological and clinical findings.Results: A final diagnosis was obtained at 93 sites in 35 patients by histology and in 5 patients by clinical follow up of at least 6 months. Of the 93 sites, 53 were determined to be malignant and 40 benign. FDG-PET evaluated on a 5-point scale (0-4) showed a positive and negative predictive value in the range of 96-98% and 83-93% respectively as the threshold for positivity was moved from 0 through 3. By comparison, CT, also evaluated on a 5-point scale showed a positive and negative predictive value in the range of 75-88% and 67-71% respectively. The area under the fitted receiver operating characteristic curve for PET: A(PET) = 0.96 +/- 0.02 was significantly greater (P < 0.001) than that observed for CT: A(CT) = 0.77 +/- 0.06. The distribution of maximum standardized uptake value (SUVmax) showed that all negative lesions have SUVmax below 5.0 whereas 75% of positive lesions were above 5.0 pointing to the fact that disease positivity is more likely in lesions with high SUV values.Conclusion: The results of this study confirm that whole-body FDG-PET is more accurate than conventional CT in the staging of patients with suspected recurrent colorectal carcinoma.

Journal Article↗
PubMed2000

Efficient cotransduction of tumors by multiple herpes simplex vectors: implications for tumor vaccine production.

Many gene therapy strategies would be enhanced by efficient transfer of multiple genes into the same cell. Herpes simplex viral amplicon (HSV) vectors are good vehicles for gene transfer because they accommodate large pieces of foreign DNA and transfer genes rapidly and efficiently. The current studies examine whether efficient cotransduction of tumor cells can be accomplished using multiple HSV vectors in a manner useful for clinical gene therapy. Interleukin-12 (IL-12) exists as a heterodimer, with components (m35 and m40) coded for by genes on two separate chromosomes. We constructed HSV vectors carrying either IL12m35 (HSVm35) or IL12m40 (HSVm40) or both genes (HSVm75) separated by an internal ribosome entry site to assess whether gene transfer using a single HSV vector constructed to carry multiple genes has any advantage over gene transfer using multiple vectors that are each carrying single genes. Because IL-12 and IL-2 have been found to have synergistic antitumoral activity, we further analyzed the biologic activity of tumor cells cotransduced by separate HSV vectors carrying genes coding for these two cytokines. The results demonstrate that multiple genes can be inserted into the same cell efficiently using multiple HSV vectors, and that these vectors allow rapid production of tumor vaccines expressing multiple cytokine genes. Thus, gene transfer using HSV may not be limited by the size of the DNA that each vector can accommodate. Immunizations with tumors cotransduced with HSVm35 and HSVm40 were equally effective in eliciting a cytolytic T-lymphocyte response and in protecting against tumor growth in vivo as immunization with tumors treated with HSVm75. Immunization with tumors cotransduced with HSVm75 and HSVil2 was superior to immunization with tumors transduced with either alone. The combination of IL-2- and IL-12-secreting tumor cells may be used as an effective immunization strategy against solid tumors.

Animals↗
PubMed2000

Combination gene therapy using multiple immunomodulatory genes transferred by a defective infectious single-cycle herpes virus in squamous cell cancer.

Herpes simplex type 2-defective infectious single-cycle (DISC) viruses are attenuated viruses that were originally produced as viral vaccines; however, these viruses are also efficient gene transfer vehicles. The main goals of this study were to examine determinants of the gene transfer by using DISC virus for squamous cancer and to evaluate the antitumoral efficacy of vaccination with tumor cells modified by DISC viruses carrying a combination of immunomodulatory genes (interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF), B7-1) in a model of squamous cell cancer (SCCVII) in C3H/HeJ mice. SCCVII cells transduced by DISC viruses (multiplicity of infection of 10) carrying the IL-2 or GM-CSF gene produced nanogram quantities of IL-2 or GM-CSF per 10(6) cells. Irradiated (5,000 cGy, 10,000 cGy) cells secreted levels of GM-CSF or IL-2 that were comparable with nonirradiated cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-IL2 or DISC-GMCSF resulted in protection against subsequent tumor challenge (P < .01), with DISC-GMCSF-transduced, irradiated tumor cells showing the greatest effects (P < .001). Marked growth arrest also was noted in established tumors after direct injection of DISC-GMCSF (P < .001). These data demonstrate that (a) DISC virus is capable of efficient gene transfer, (b) GM-CSF-secreting genetically modified tumor vaccine protects against tumor cell challenge and suppresses tumor growth, and (c) intratumoral injection of DISC-GMCSF significantly suppresses the growth of established tumors. These results not only confirm clinically relevant gene transfer but also demonstrate that the gene transfer is an effective anti-cancer therapy.

Animals↗
PubMed2000

Regional muramyl tripeptide phosphatidylethanolamine administration enhances hepatic immune function and tumor surveillance.

BACKGROUND: Immune status of the liver may affect growth of liver metastases. We analyzed the ability of muramyl tripeptide phosphatidylethanolamine (MTP-PE), an immunomodulatory bacterial cell wall analog, to stimulate Kupffer cells (KCs) and protect against tumor growth, with or without an immunosuppressive partial hepatectomy (PH). Impact of MTP-PE's route of administration on KC function was assessed. METHODS: Buffalo rats (n = 7 to 12/group) were treated with saline, 40 microg MTP-PE intraportally (portal) or intravenously (IV) and challenged with 5 x 10(5) hepatoma cells, and tumors counted on day 21. To assess MTP-PE's impact on KC stimulation in animals undergoing PH, a known stimulant of tumor cell growth, groups were treated with saline or MTP-PE and challenged with tumor and underwent 30% PH. KCs were harvested and analyzed for superoxide production. Statistical analysis was performed with Mann-Whitney U test or chi-square test. RESULTS: MTP-PE-treated animals had fewer tumor nodules than control animals (19 vs 184, P <.005). MTP-PE-portal animals had fewer nodules than MTP-PE-IV (2 vs 36, P <.05). MTP-PE treatment before PH resulted in fewer tumor nodules compared with control animals (192 vs 276, P <. 05). MTP-PE administration increased macrophage superoxide production (20.6 +/- 2 vs 11.9 +/- 1.1 nmol/10(6) cells, P <.005). CONCLUSIONS: MTP-PE improved KC function and decreased growth of microscopic tumor cells. MTP-PE's effects persist after an immunosuppressive hepatectomy. Portal administration was the most effective. MTP-PE administration may be useful as a neoadjuvant therapy for patients undergoing resection of liver malignancies.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2000

Neoadjuvant interleukin-12 immunogene therapy protects against cancer recurrence after liver resection in an animal model.

OBJECTIVE: To evaluate the neoadjuvant use of a herpes simplex viral (HSV) amplicon vector expressing the murine interleukin-12 (IL-12) gene. SUMMARY BACKGROUND DATA: Surgery is the most effective therapy for hepatic malignancy. Recurrences, which are common, most often occur in the remnant liver and are due partly to growth of residual microscopic disease in the setting of postoperative host cellular immune dysfunction. The authors hypothesized that engineering tumors to secrete IL-12 in vivo would elicit an immune response directed at residual tumor and would reduce the incidence of recurrence after resection. METHODS: Solitary hepatomas were established in Buffalo rat livers and directly injected with 106 particles of HSV carrying the gene for IL-12, lacZ (beta-galactosidase) or with saline. One week after injection, the animals were challenged with an intraportal injection of 106 tumor cells, with subsequent resection of the hepatic lobe containing the previously established macroscopic tumor nodule, recreating the clinical scenario of residual microscopic cancer. RESULTS: Hepatoma cells transfected with HSV-IL-12 produced high levels of IL-12 in vitro and in vivo. A significant local immune response developed, as evidenced by a progressive increase in the number of CD4(+) and CD8(+) lymphocytes in the tumor. Treatment of established hepatomas with HSV-IL-12 protected against growth of microscopic residual cancer after hepatic resection. Sixty-four percent of the animals treated with HSV-IL-12 had zero or one tumors compared with 30% of HSVlac-treated and 24% of saline-treated animals. CONCLUSIONS: This neoadjuvant immune strategy may prove useful in reducing the incidence of cancer recurrence after hepatic resection.

Animals↗
PubMed2000

Gallbladder cancer: comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention.

OBJECTIVE: To compare patients with gallbladder cancer presenting for therapy with and without prior operation elsewhere to determine if an initial noncurative procedure alters outcome. SUMMARY BACKGROUND DATA: Nihilism has traditionally surrounded treatment of gallbladder cancer, particularly since the majority of cases are discovered during exploration for presumed gallstone disease when unsuspected cancers cannot be handled definitively and tumor is often violated. METHODS: Presentation, operative data, complications, and survival were examined for 410 patients presenting between July 1986 and March 2000. In particular, the 248 patients presenting for therapy after prior operation elsewhere were compared with the remainder who presented without prior operation to determine if an initial noncurative procedure alters outcome. RESULTS: Overall Outcome: 51 patients were inoperable, 92 were subjected to exploration and biopsy only, 135 to noncurative cholecystectomy, 30 to surgical bypass, and 102 to potentially curative resections consisting of portal lymph node dissection and liver parenchymal resections. Operative mortality was 3.9%. T-stage predicted likelihood of distant metastases and resectability. Median survival for resected patients was 26 months and 5-year survival was 38%, and for patients not resected, 5.4 months and 4% (P <.0001). Effect of Prior Operation: 22 patients subjected to potentially curative resection as the first surgical procedure were compared to 80 patients resected after prior exploration elsewhere. Mortality, complication, and long-term survival were the same. By multivariate analysis (Cox regression), resectability and stage were independent predictors (P <.001) of long-term survival, but prior surgical exploration was not. CONCLUSION: Unresected gallbladder cancer is a rapidly fatal disease. Radical resection can provide long-term survival, even for large tumors with extensive liver invasion. Long-term survival can be achieved for patients presenting after prior noncurative surgical exploration.

Aged↗