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Biomedical subjects

S A Curley

Publications and source records attributed to S A Curley.

At least 37 records · Page 2Linked to original sources
PubMed1999

Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients.

OBJECTIVE: To describe the safety and efficacy of radiofrequency ablation (RFA) to treat unresectable malignant hepatic tumors in 123 patients. BACKGROUND: The majority of patients with primary or metastatic malignancies confined to the liver are not candidates for resection because of tumor size, location, or multifocality or inadequate functional hepatic reserve. Local application of heat is tumoricidal; therefore, the authors investigated a novel RFA system to treat patients with unresectable hepatic cancer. PATIENTS AND METHODS: Patients with hepatic malignancies were entered into a prospective, nonrandomized trial. The liver tumors were treated percutaneously or during surgery under ultrasound guidance using a novel LeVeen monopolar array needle electrode and an RF 2000 generator. All patients were followed to assess complications, treatment response, and recurrence of malignant disease. RESULTS: RFA was used to treat 169 tumors (median diameter 3.4 cm, range 0.5 to 12 cm) in 123 patients. Primary liver cancer was treated in 48 patients (39.1%), and metastatic liver tumors were treated in 75 patients (60.9%). Percutaneous and intraoperative RFA was performed in 31 patients (35.2%) and 92 patients (74.8%), respectively. There were no treatment-related deaths, and the complication rate after RFA was 2.4%. All treated tumors were completely necrotic on imaging studies after completion of RFA treatments. With a median follow-up of 15 months, tumor has recurred in 3 of 169 treated lesions (1.8%), but metastatic disease has developed at other sites in 34 patients (27.6%). CONCLUSIONS: RFA is a safe, well-tolerated, and effective treatment to achieve tumor destruction in patients with unresectable hepatic malignancies. Because patients are at risk for the development of new metastatic disease after RFA, multimodality treatment approaches that include RFA should be investigated.

Adult↗
PubMed1999

Laparoscopy in 533 patients with abdominal malignancy.

BACKGROUND: Laparoscopy in patients with intra-abdominal malignancy remains controversial. This study evaluates the incidence of tumor recurrence at the port site after laparoscopy in patients with intra-abdominal malignancy. METHODS: The medical records of all patients with nongynecologic malignancies who underwent laparoscopic procedures between May 1, 1990, and June 30, 1996, at the University of Texas M.D. Anderson Cancer Center were reviewed. Data on extent of tumor, histologic findings, primary location, procedures performed, and complications were recorded. RESULTS: During this time, 533 patients with known intra-abdominal malignancies underwent laparoscopy. Mean follow-up time was 13.2 +/- 0.5 months (range 1 to 71 months; median 10.6 months). Four recurrences at the port site were identified (0.8%). Three of these patients had advanced intra-abdominal disease at the time of laparoscopy; 1 patient without advanced disease at the time of laparoscopy had a recurrence at the port site as the only site of recurrent disease (0.19%). The incidence of port site recurrences among patients with advanced intra-abdominal disease at the time of laparoscopy (3/71) was significantly greater than the risk of development of a recurrence at the port site among patients without advanced intra-abdominal disease at the time of laparoscopy (1/462; P < .0003, by chi-square analysis). CONCLUSION: Recurrence at the port site is very rare. When implantation at the port site does occur, it is most commonly associated with advanced intra-abdominal disease.

Abdominal Neoplasms↗
PubMed1998

Clinical, pathologic, and economic parameters of laparoscopic colon resection for cancer.

BACKGROUND: The appropriateness of laparoscopic colon resection (LCR) as treatment for malignancy has been questioned. METHODS: From 1992 to 1997, 91 patients were entered into a prospective study of LCR for cancer. Clinical, pathologic, and economic parameters of LCR were compared in a cohort of patients matched for age, tumor stage, and type of colectomy who underwent open colon resection (OCR) during the same time period. RESULTS: With a median follow-up of 26 months, there were no significant differences in survival rate for patients in the LCR, converted colon resection, and OCR groups. There were no port-site recurrences and the number of lymph nodes harvested was similar among the procedures. Hospital stay was significantly shorter if laparoscopic resection was successful. Total hospital costs were similar for LCR and OCR; however, the costs were significantly higher for converted colon resection. CONCLUSIONS: LCR is a sound oncologic procedure that can be performed with costs similar to OCR.

Adult↗
PubMed1998

Surgical decision-making affected by clinical and genetic screening of a novel kindred with von Hippel-Lindau disease and pancreatic islet cell tumors.

OBJECTIVE: We report a unique, previously undescribed multigeneration kindred with von Hippel-Lindau (VHL) disease in whom clinical or genetic screening led to the detection of surgically resectable neoplastic disease in several family members. SUMMARY BACKGROUND DATA: Patients with VHL disease have a propensity to develop neoplasms of several different organ sites. Retinal angiomas, cerebellar and spinal hemangioblastomas, solid organ cysts, and renal carcinoma are common lesions; pheochromocytomas and pancreatic islet cell tumors occur less frequently but are important causes of morbidity and mortality. METHODS: A detailed pedigree was constructed based on clinical screening and family history that describes the development of pancreatic islet cell tumors in four of five female siblings. VHL mutation analysis was performed in an attempt to determine if genotype-phenotype correlations could be made in this interesting family. RESULTS: The age of onset of VHL-associated neoplasms for three affected siblings was in the third decade of life and in the fourth decade for the fourth sibling. The mother of the four siblings affected with pancreatic tumors developed bilateral pheochromocytomas in the seventh decade of life; she has no pancreatic or kidney tumors. We identified maternal transmission of a missense mutation in codon 238 in exon 3 of the VHL gene in the four affected siblings with pancreatic islet cell tumors. Mutation screening on unaffected family members showed no abnormalities in the VHL gene. Interestingly, one of the four affected siblings had no evidence of VHL on her initial clinical screening evaluation; however, she was followed closely because of her mutated VHL gene. Four years after initial screening, she developed two pancreatic islet cell tumors and a premalignant renal cyst. CONCLUSIONS: Clinical and genetic screening for VHL in this family had a significant impact on surgical management by detecting early-stage islet cell tumors or pheochromocytomas. Furthermore, we conclude that the preponderance of pancreatic islet cell tumors in this family cannot be explained by a strict genotype-phenotype correlation. This suggests that additional genetic abnormalities, possibly on chromosome 3p where the VHL gene is located, may be responsible for the variety of VHL-associated neoplasms.

Adenoma, Islet Cell↗
PubMed1998

Outcome of 67 patients with hepatocellular cancer detected during screening of 1125 patients with chronic hepatitis.

OBJECTIVE: We performed this prospective screening trial in chronic hepatitis virus-infected patients to determine the incidence of hepatocellular cancer (HCC) and the resectability and long-term survival rates of these HCC patients. SUMMARY BACKGROUND DATA: Chronic hepatitis B or C virus infection is a major etiologic factor in human HCC. It is not clear if routine screening of chronic viral hepatitis patients improves the survival of patients who develop HCC. METHODS: Screening for HCC was offered to patients chronically seropositive (>5 years) for hepatitis B or C infection. All patients underwent percutaneous core liver biopsy to assess the histologic severity of chronic liver injury. Patients were screened initially and every 3 months thereafter with serum alpha-fetoprotein and transabdominal ultrasound evaluations; HCC was confirmed by needle biopsy of liver tumors. RESULTS: Screening was performed on 1125 hepatitis-positive patients (804 with hepatitis C, 290 with hepatitis B, 31 with both). On liver biopsy, 800 patients had mild chronic active hepatitis and 325 had severe chronic active hepatitis, cirrhosis, or both. Initial screening detected HCC in 61 patients. HCC was detected in six more patients during follow-up; thus, the incidence of HCC was 5.9% (67/1125). However, 66 of the 67 HCC cases (98.5%) arose in the 325 patients with severe chronic active hepatitis or cirrhosis (66/325 [20.3%] vs. 1/800 [0.1%], p < 0.0001 [Wilcoxon signed rank]). Median follow-up of the 67 HCC patients was 24 months. Locally advanced or metastatic, unresectable HCC occurred in 43 patients (64.2%); 24 patients (35.8%), including the 6 patients detected during follow-up screening, underwent margin-negative resection. The median survival for the 24 resected patients was 26 months, compared to 6 months for the 43 patients with unresectable cancer (p < 0.0001, Wilcoxon signed rank). CONCLUSIONS: HCC was found to arise in 20.3% of patients with chronic hepatitis B or C infection and severe liver injury. Initial screening detected resectable lesions in less than half the HCC patients. Routine screening of chronic hepatitis B or C virus-infected patients with ultrasound and alpha-fetoprotein determination should be reserved for patients with severe chronic active hepatitis, cirrhosis, or both.

Adult↗
PubMed1998

Enhanced Krev-1 expression inhibits the growth of pancreatic adenocarcinoma cells.

Pancreatic ductal adenocarcinoma is characterized by a high rate of activating mutations involving codon 12 of the K-ras protooncogene. As a means of ras-targeted intervention, the effects of enhanced Krev-1 gene expression on the growth and tumorigenicity of the hamster pancreatic adenocarcinoma cell line PC-1 were evaluated. Overexpression of the Krev-1 gene product resulted in morphologic reversion to a less transformed phenotype, as well as retarded growth kinetics and diminished potential for anchorage-independent growth. Among six transfected cell lines, the magnitude of these changes correlated with the degree of Krev-1 overexpression as assessed by Western blot. When PC-1 cells overexpressing high levels of the Krev-1 gene product were assessed for tumorigenicity in syngeneic animals, an increased latency to tumor growth and a decreased tumor size were noted. The results confirm that overexpression of the Krev-1 gene may provide a useful strategy for ras-targeted intervention in this disease.

Adenocarcinoma↗
PubMed1998

The management of gallbladder cancer: before, during, and after laparoscopic cholecystectomy.

Carcinoma of the gallbladder is a rare disease, but when encountered in the patient undergoing laparoscopic cholecystectomy, it can pose a number of dilemmas. Familiarity with the risk factors for malignant gallbladder disease can help identify patients in whom more extensive preoperative evaluation is warranted. When carcinoma is identified preoperatively, cholecystectomy should be performed as an open procedure. If malignancy is encountered unexpectedly during laparoscopic cholecystectomy, the procedure should be converted to an open resection to allow for appropriate evaluation of the stage of disease and appropriate surgical management. Most commonly, malignancy is identified postoperatively, only after pathological examination of the resected gallbladder. Except in rare circumstances, open reoperation is necessary to achieve an adequate curative resection. The current concerns about port site recurrence and carcinomatosis after laparoscopic resection of a gallbladder carcinoma are unwarranted based on current published data. The role of prophylactic excision or irradiation of port sites is uncertain based on current understanding of the biological behavior of the disease.

Cholecystectomy, Laparoscopic↗
PubMed1998

Primary pancreatic lymphoma.

BACKGROUND: Primary pancreatic lymphoma is a rare neoplasm that may be confused with pancreatic adenocarcinoma. We reviewed retrospectively our contemporary experience with this disease to define more clearly the clinical presentation of this disease and the proper role for percutaneous fine-needle aspiration biopsy and surgery. METHODS: From 1980 to 1995, 11 patients with primary pancreatic lymphoma were treated at The University of Texas M. D. Anderson Cancer Center. Patient demographics, radiographic studies, fine-needle aspiration biopsy findings, operative procedures, and other treatment data were reviewed. RESULTS: The median age of the 11 patients was 64 years (range, 37 to 74 years). Abdominal pain was the most common symptom at presentation. Five patients had an elevated lactate dehydrogenase level, and only two patients had hyperbilirubinemia. Computed tomography scan demonstrated encasement of the superior mesenteric artery or superior mesenteric-portal vein confluence in six patients. Seven patients underwent computed tomography-guided fine-needle aspiration; five had findings of lymphoma. Two patients underwent distal pancreatectomy and splenectomy, and one underwent pancreaticoduodenectomy. All patients were treated with combination chemotherapy, and seven received radiotherapy. Only two patients have died of disease (12 and 16 months after diagnosis) at a median follow-up time of 67 months. CONCLUSIONS: In the majority of patients, pancreatic lymphoma can be distinguished from pancreatic adenocarcinoma on the basis of symptoms, laboratory and radiographic findings, and fine-needle aspiration biopsy results. Once the diagnosis is established, all patients should undergo systemic chemotherapy followed by involved-field radiotherapy if the tumor has not been resected.

Adult↗
PubMed1997

Carcinoid tumors of the rectum: effect of size, histopathology, and surgical treatment on metastasis free survival.

BACKGROUND: The purpose of this study was to determine the clinical course, effects of specific tumor histopathologic characteristics, and extent of surgical treatment on the metastatic rate in patients with rectal carcinoids. METHODS: Medical records of 44 patients who presented with rectal carcinoids were retrospectively reviewed. Primary tumors were classified by size (< 1 cm, 1-2 cm, and > 2 cm), and tumor histopathologic features (atypical or typical). Extensive surgery was defined as abdominoperineal or low anterior resection of the rectum or laparotomy with intent of curative resection. RESULTS: Median follow-up for patients who presented without metastasis was 84 months. Thirteen of the 44 patients (30%) presented with metastatic disease. The 5-year metastasis free survival rates for those patients presenting without metastatic disease were 100% for patients with tumors < 1 cm (n = 16), 73% for those with tumors 1-2 cm (n = 8), and 25% for those with tumors > 2 cm (n = 4) (P = 0.04 comparing < 1 cm with 1-2 cm and P = 0.05 comparing 1-2 cm with > 2 cm); tumor size data were not available for 3 patients. The 5-year metastasis free survival rate for patients presenting without metastatic disease with typical histology (n = 20), regardless of size, was 100%, compared with 50% for patients with tumors with atypical histology (n = 11) (P = 0.001). Nine patients underwent extensive surgery for rectal carcinoid tumors but no survival benefit was demonstrated. CONCLUSIONS: Atypical histopathologic features and a tumor size > 1 cm are associated with aggressive behavior of rectal carcinoid tumors. Extensive surgery offers no survival advantage over local excision for patients with rectal carcinoid tumors.

Adult↗
PubMed1997

Repeat hepatic resection as effective treatment of recurrent colorectal liver metastases.

BACKGROUND: Approximately 20-40% of patients who undergo liver resection for colorectal metastases develop recurrent disease confined to the liver. The goals of this study were to determine whether the survival benefit of repeat hepatic resection justified the potential morbidity and mortality. METHODS: A retrospective review was performed on all patients who underwent liver resection for colorectal cancer metastases between 1983 and 1995 (N = 202). Repeat liver resections were performed on 23 patients for recurrent metastases. RESULTS: There were no operative deaths in the 23 patients, and the postoperative morbidity rate was 22%. The 5-year actuarial survival rate after repeat resection was 32%, with a median length of survival of 39.9 months. There were three patients who survived for > 5 years after repeat resection. Sixteen patients (70%) developed recurrent disease at a median interval of 11 months after the second resection; 10 of these 16 patients (62%) had new hepatic metastases. No clinical or pathological factors were significant in predicting long-term survival. CONCLUSIONS: Repeat liver resection for recurrent colorectal metastases (a) can be performed safely with acceptable mortality and morbidity rates and (b) may result in long-term survival in some patients.

Adult↗
PubMed1997

Activation of human Kupffer cells by thymostimulin (TP-1) to produce cytotoxicity against human hepatocellular cancer.

BACKGROUND: In a small pilot study, thymostimulin (TP-1) produced tumor regression in almost 50% of patients with hepatocellular cancer (HCC) who were treated with TP-1 alone. However, the mechanism of the TP-1-mediated antitumor effect against HCC is unknown. METHODS: Human hepatocytes and Kupffer cells were isolated from liver biopsy specimens by collagenase infusion and counterflow elutriation. Hepatocytes and Kupffer cells were incubated in vitro with clinically relevant doses of TP-1. Cell-free supernatant levels for a panel of growth factors and monokines were determined by enzyme-linked immunosorbent assay. The cytotoxic activity of TP-1 alone of TP-1-stimulated hepatocyte and Kupffer cell supernatants against Hep G2 and Hep 3B human HCC cells in vitro was measured by MIT assay. RESULTS: Doses of TP-1 up to 100 micrograms/ml produced no cytotoxicity against Hep G2 or Hep 3B cells. Furthermore, supernatants from TP-1-treated hepatocytes produced no cytotoxicity against Hep G2 or Hep 3B cells, and TP-1 did not stimulate the release of transforming growth factor (TGF)-alpha, TGF-beta, or hepatocyte growth factor. TP-1-treated Kupffer cell supernatants produced significant cytotoxicity against Hep G2 cells but produced no cytotoxicity against Hep 3B cells. Kupffer cells stimulated by TP-1 released significant amounts of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 alpha, and IL-6 compared with control Kupffer cells (p < 0.01). The activity of TP-1-treated Kupffer cell supernatants against Hep G2 cells was blocked by anti-TNF-alpha antibodies, whereas neither anti-IL-1 alpha nor anti-IL-6 antibodies blocked cytotoxicity. CONCLUSIONS: These results demonstrate that TP-1 cytotoxicity against human HCC cells is not mediated directly or through hepatocytes, but occurs through activation of Kupffer cells and release of TNF-alpha. Understanding the mechanism of TP-1 cytotoxicity against human HCC has been used to plan a phase 1 trial of TP-1 combined with regional infusion of doxorubicin to treat unresectable HCC.

Adjuvants, Immunologic↗
PubMed1997

Laparoscopically guided bipolar radiofrequency ablation of areas of porcine liver.

BACKGROUND: Bipolar radiofrequency ablation (BRFA) is a promising technique with which to treat unresectable primary and metastatic liver tumors. Its effects on normal liver tissue and postoperative liver function, however, are unknown. We performed this study to determine (1) the feasibility of using laparoscopic ultrasound to guide placement of BRFA needle electrodes in the liver and (2) the histopathologic, hepatic biochemical, and systemic hemodynamic responses to BRFA. METHODS: Two BRFA lesions were created in the liver of adult domestic pigs to ablate 8-10% of the normal liver volume. Laparoscopic ultrasound was used to guide creation of one peripheral liver lesion and one central liver lesion (with a major hepatic or portal venous vein branch in the center of the BRFA lesions) in each animal. BRFA of liver tissue was performed by passing 12 W of RF power for 16 min across two 16-gauge active-needle electrodes placed 3 cm apart. RESULTS: All animals survived the procedure without significant hemodynamic alterations during or after BRFA. All animals had a transient elevation in serum transaminase levels that returned to normal within 1 week of the BRFA of liver tissue. Gross and microscopic histopathology of the BRFA lesions revealed 2.0-2.5-cm zones of complete coagulative necrosis around and between the BRFA needle tracks without destruction of major blood vessel walls. CONCLUSIONS: This study demonstrates (1) that laparoscopic ultrasound can be used to guide placement of BRFA needles in the liver and (2) that BRFA produces focal destruction of liver without significant systemic hemodynamic responses or alterations in liver function. Further studies of this technique to ablate malignant liver tumors are ongoing.

Animals↗
PubMed1997

Gallbladder cancer and trocar site recurrences.

BACKGROUND: Critics of laparoscopic surgery cite an increased incidence of tumor recurrence at the trocar sites following laparoscopic cholecystectomy in patients incidentally found to have carcinoma of the gallbladder. The purpose of this review was to determine if laparoscopic cholecystectomy performed in patients with gallbladder cancer results in an increased incidence of abdominal wall recurrences. METHODS: The charts of all patients with gallbladder cancer registered at the University of Texas M. D. Anderson Cancer Center from January 1991 through April 1996 were retrospectively reviewed. Data were collected on initial and subsequent surgical procedures, tumor grade and histology, T stage, adjuvant therapy, and survival. These data were analyzed with regard to abdominal wall recurrences and outcome. RESULTS: Ninety-three patients with gallbladder cancer were seen during this period; 79 patients with complete follow-up information comprised the study population. Comparison of the incidence of abdominal wall recurrences among the categories of surgical procedure (laparoscopic versus open versus laparoscopic converted to open) did not reveal any statistically significant differences. Overall 5-year survival was 10%. CONCLUSIONS: Gallbladder cancer is an aggressive malignancy with few long-term survivors. In addition, these data show that the incidence of abdominal wall implantation is not increased with laparoscopic surgery but is more likely a manifestation of the aggressive nature of this tumor.

Abdominal Muscles↗
PubMed1997

Neoadjuvant chemoradiation for extrahepatic cholangiocarcinoma.

BACKGROUND: The prognosis for patients with extrahepatic bile duct cancer remains poor. The purpose of this study was to evaluate our initial results with preoperative chemoradiation for extrahepatic cholangiocarcinoma, in the context of our experience with conventional treatment of this disease over the past 13 years. METHODS: From 1983 through 1996, analysis of all patients treated for extrahepatic cholangiocarcinoma was performed. RESULTS: Of 91 total patients, 51 had unresectable disease and 40 underwent resection. Median survival was significantly different for patients who underwent resection (22.2 months) versus those treated palliatively (10.7 months; P <0.0001). Nine patients underwent preoperative chemoradiation (5 perihilar, 4 distal) prior to resection. Three patients in the preoperative chemoradiation group had a pathologic complete response, while the remainder showed varying degrees of histologic response to treatment. The rate of margin-negative resection was 100% for the preoperative chemoradiation group versus 54% for the group who did not receive preoperative chemoradiation (P <0.01). There were no major intra-abdominal complications in the patients treated with preoperative chemoradiation. CONCLUSIONS: These results suggest that preoperative chemoradiation for extrahepatic bile duct cancer can be performed safely, produces significant antitumor response, and may improve the ability to achieve tumor-free resection margins. Additional trials of preoperative chemoradiation are warranted.

Adult↗
PubMed1997

Safe anesthetic management of patients undergoing a novel method of treating human hepatocellular cancer.

STUDY OBJECTIVE: To evaluate the safety and efficacy of monitored anesthesia care (MAC) in patients who undergo a novel treatment for hepatocellular cancer in which procedure-related hemodynamic instability is problematic. DESIGN: Nonrandomized open study. SETTING: University cancer center operating room. PATIENTS: Nine patients scheduled for hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration (no more than 3 procedures per patient). INTERVENTIONS: Hepatic venous isolation was achieved with a dual-balloon inferior vena cava catheter connected to an extracorporeal circuit containing chemofilters. Doxorubicin was infused through the hepatic artery and filtered from the venous blood, which was returned to the patient through an internal jugular venous catheter. Each patient received a bolus of propofol (200 micrograms/kg) and one of alfentanil (2 micrograms/kg) followed by simultaneous infusions of propofol and alfentanil for percutaneous placement of the catheters and operation of the extracorporeal circuit. Drug rates were varied to maintain a sedative-analgesic state of calm, comfort, minimal movement, and adequate respiratory function. Prior to circuit initiation, patients were preloaded with crystalloid. During circuit operation, hypotension was treated with intravenous (IV) phenylephrine and crystalloid. MEASUREMENTS AND MAIN RESULTS: End-tidal CO2 (PETCO2), respiratory rate, oxygen saturation (SaO2), arterial blood pressure (BP), and heart rate (HR) were monitored. Systolic, diastolic, and mean arterial pressure (MAP), and HR were compared before, during, and after hepatic venous isolation and chemofiltration. Doses and infusion rates of propofol, alfentanil, and phenylephrine were recorded for each treatment. Hypotension occurred in 11 of 13 procedures when blood was directed through the chemofilters and was successfully treated with phenylephrine (dose range 40 to 5,733 micrograms) and crystalloid. Blood pressure returned to the baseline value on termination of the circuit. Throughout the sedation, patients were easily arousable, analgesia was adequate, and PETCO2 level of 38 +/- 4 mmHg and SaO2 greater than 94% were maintained. Mean doses and infusion rates of MAC drugs were, respectively: propofol, 261 +/- 88 mg and 23.7 +/- 3.6 micrograms/kg/min; alfentanil, 3,350 +/- 1,468 micrograms and 0.32 +/- 0.14 microgram/kg/min. CONCLUSIONS: Patients undergoing this novel cancer treatment are safely and effectively managed by MAC achieved with simultaneous infusions of alfentanil and propofol. Procedure-associated hypotension is easily treated with IV phenylephrine and crystalloid.

Adrenergic alpha-Agonists↗
PubMed1996

Frequent coordinated overexpression of the MRP/GS-X pump and gamma-glutamylcysteine synthetase genes in human colorectal cancers.

We have recently shown that multidrug resistance-associated protein (MRP) and gamma-glutamylcysteine synthetase (gamma-GCS) heavy subunit genes are coordinately overexpressed in cisplatin-resistant human leukemia cells (T. Ishikawa et al. J. Biol. Chem., 271: 14981-14988, 1996). Using the RNase protection assay, we examined expression levels of these genes in colon tumor and nontumorous biopsy specimens from 32 cancer patients who had not been treated with chemotherapy. Increased mRNA levels (P < 0.001) of MRP and gamma-GCS genes were observed in 16 (50%) and 20 (62%) tumor samples, respectively. More importantly, all of the 16 (100%) MRP-overexpressing tumor specimens also exhibited higher levels of gamma-GCS mRNA than those in the matched nontumorous specimens. The correlation coefficient between MRP and gamma-GCS mRNA levels was r = 0.78 for all of the tumor samples studied. These results strongly suggest that MRP and gamma-GCS genes are coordinately up-regulated during colorectal carcinogenesis.

ATP-Binding Cassette Transporters↗
PubMed1996

Alternating floxuridine and 5-fluorouracil hepatic arterial chemotherapy for colorectal liver metastases minimizes biliary toxicity.

BACKGROUND: The goals of this study of a hepatic arterial infusion (HAI) regimen of alternating floxuridine and 5-fluorouracil were to evaluate the treatment-related toxic effects, the antitumor response rate, and patient survival. METHODS: Fifty-seven consecutive patients were treated with implanted HAI pumps and received a regimen of alternating floxuridine (0.1 mg/kg/day continuous HAI for 7 days) followed by a weekly HAI pump bolus of 5-fluorouracil (15 mg/kg for 3 weeks). Any changes in treatment plan because of toxicity, antitumor response, and survival were recorded. RESULTS: Thirty-one (54.4%) patients responded to this HAI regimen; 14 (24.5% )patients had stable disease, and 12 (21.1%) progressed during treatment. Responders or patients with stable disease had a significantly (P < 0.05) improved survival rate (19 months median) compared with patients in whom disease progressed (12 months median). Two (3.5%) patients developed biliary sclerosis and 12 (21.1%) had mild transient liver function abnormalities. The liver alone or in combination with another area was the site of first progression of disease in 40 (70.2%) patients. CONCLUSIONS: This regimen had reversible or no hepatobiliary toxicity in more than 95% of patients. Tumor reduction or stabilization of disease was observed in 79% of the patients, who had a median survival of 19 months. Reduced toxicity and more effective chemotherapeutic regimens may increase the likelihood of survival after HAI chemotherapy for unresectable colorectal liver metastases.

Adult↗