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Biomedical subjects

S A Curley

Publications and source records attributed to S A Curley.

At least 73 records · Page 4Linked to original sources
PubMed1994

Hepatic arterial infusion of verapamil and doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration: pharmacological evaluation of reduction in systemic drug exposure and assessment of hepatic toxicity.

Tumour resistance to chemotherapeutic drugs through expression of the multidrug resistance phenotype is a major impediment in the treatment of hepatic malignancies. We performed hepatic arterial infusion of verapamil (at a dose known to block P-glycoprotein activity) and doxorubicin combined with complete hepatic venous isolation and extracorporeal chemofiltration in non-tumour-bearing pigs with normal livers to evaluate the pharmacology and toxicology of this drug combination. The complete hepatic venous isolation-chemofiltration system significantly reduced system exposure to both verapamil and doxorubicin (P < 0.01). Hepatic arterial infusion of verapamil (2 mg/kg) alone did not result in hepatocellular toxicity. However, the combination of verapamil and doxorubicin (3 mg/kg or 5 mg/kg) produced significant elevations in liver enzymes (P < 0.01), and gross histological evidence of liver damage in 90% of the treated animals. The results of this study indicate that hepatic arterial infusion of verapamil and doxorubicin, in an attempt to improve treatment response in unresectable liver tumours expressing the multidrug resistance phenotype, may not be tolerated by patients with limited hepatic reserve.

Animals↗
PubMed1994

Adjuvant radiotherapy and chemotherapy for biliary and pancreatic cancer.

Due to the limited efficacy of surgery in pancreatico-biliary cancer, perioperative treatment modalities are of high clinical interest. Adjuvant chemoradiation with protracted infusion 5-FU for these tumors is an attractive direction for continued clinical research and may increase local control. Improved local control may influence survival as has been demonstrated by the results of adjuvant chemoradiation for operable rectal cancer. Newer combinations of chemotherapy and external beam radiotherapy (ExBRT) will need to be tested. The results of combined modality therapy indicate that increased normal tissue reactions occur and caution must be exercised during treatment especially in the areas of nutrition and fluid balance. New treatment strategies with electron beam IORT are also investigating higher doses of radiotherapy than those achieved with ExBRT alone in order to achieve better permanent tumor eradication. Data from our institution have demonstrated the safety of aggressive preoperative chemoradiation, surgical resection and IORT. Prophylactic hepatic and whole abdominal chemoradiation for occult liver disease needs further testing in clinical trials, since the liver is the single most frequent site of failure outside the primary site.

Antineoplastic Agents↗
PubMed1994

Resection for cure of carcinoma of the colon directly invading the duodenum or pancreatic head.

BACKGROUND: Approximately 10 percent of carcinomas of the colon and rectum adhere to adjacent organs or structures, which rarely include the duodenum or pancreas. STUDY DESIGN: To confirm the importance of aggressive operative management in patients with locally advanced carcinoma of the colon invading the duodenum or pancreatic head, we reviewed the medical records of 12 patients who underwent an extended resection for a right-sided carcinoma of the colon involving the duodenum or the pancreatic head, or both. RESULTS: All patients underwent an extended right hemicolectomy, including en bloc pancreaticoduodenectomy (seven patients) or lateral duodenectomy (five patients). The mean operative blood loss was 627 mL, and there were no postoperative deaths. Malignant invasion of the duodenum or pancreas was confirmed in all 12 patients, but only three (25 percent) had lymph node metastases. The median survival period for all 12 patients was 32 months. However, the median survival period for the eight patients still alive without recurrent or metastatic disease was 42 months. CONCLUSIONS: In patients with locally advanced carcinoma of the colon involving the duodenum or pancreatic head long-term survival can be achieved by en bloc resection.

Adenocarcinoma↗
PubMed1993

Mechanisms of Kupffer cell cytotoxicity in vitro against the syngeneic murine colon adenocarcinoma line MCA26.

We have previously demonstrated that in vivo activation or inhibition of Kupffer cell (KC) cytotoxic function can reduce or enhance, respectively, the hepatic tumor burden in a syngeneic murine colon adenocarcinoma (MCA26) tumor model. In the current study, we have performed in vitro experiments to define the possible mechanisms of KC cytotoxicity against MCA26 cells. Addition of either anti-tumor necrosis factor (TNF) or anti-interleukin-1 alpha (IL-1 alpha) antisera reduced KC cytotoxicity in coculture against MCA26 targets in a dose-dependent fashion; addition of these sera together resulted in approximately additive inhibition, suggesting the existence of parallel pathways for these effector molecules. Nitric oxide as a mediator of cytotoxicity by KCs in coculture with MCA26 cells was evaluated by two approaches. Activated KCs produced detectable levels of nitric oxide; however, activated KC exerted cytotoxicity against MCA26 targets in the absence of exogenous free L-arginine. Thus, TNF and IL-1 play major roles in producing murine KC cytotoxicity against MCA26 colon cancer cells in vitro, whereas reactive nitric oxides do not.

Adenocarcinoma↗
PubMed1993

Site-specific differences in pp60c-src activity in human colorectal metastases.

The c-src proto-oncogene has been implicated in the progression of primary human colorectal carcinoma to hepatic metastasis. To determine if increased pp60c-src tyrosine kinase activity is a colon-specific phenomenon present in colorectal metastases to all sites, the pp60c-src-specific kinase activity of noncolon tumor metastases to the liver was compared to that of colorectal liver metastases. Activity of extrahepatic colon carcinoma metastases was compared to that of colorectal liver metastases as well as that of normal colonic mucosa. The specific activity of pp60c-src in multiple synchronous metastases from colon carcinoma was also examined. Tyrosine kinase activity was determined by immune complex kinase assay; protein levels were determined by immunoblotting. Specific activity was calculated for each group by dividing the total activity by protein level. Colon carcinoma metastases to the liver had significantly (P < 0.04) increased pp60c-src activity with an average 2.2-fold increase over normal mucosa. In contrast, noncolon tumor metastases to the liver showed minimal pp60c-src kinase activity. Extrahepatic colorectal metastases demonstrated significantly increased (P < 0.005) pp60c-src activity with an average 12.7-fold increase over normal mucosa. When compared to colon liver metastases, extrahepatic colorectal tumor metastases show a significant difference in activity (P < 0.05) with an average 5.7-fold increase. Examination of multiple synchronous colon carcinoma metastases confirmed these results. In summary, we conclude that (1) the activation of pp60c-src between primary tumors and metastases is specific to colon metastases, and (2) although pp60c-src activity is significantly increased in colorectal metastases, site-specific differences in the magnitude of activity are evident.

Adenocarcinoma↗
PubMed1993

Increased doxorubicin levels in hepatic tumors with reduced systemic drug exposure achieved with complete hepatic venous isolation and extracorporeal chemofiltration.

We evaluated a novel system of complete hepatic venous isolation and chemofiltration (CHVI-CF) to reduce systemic drug exposure following regional hepatic infusion of doxorubicin. Rabbits bearing hepatic VX-2 tumors were given doxorubicin via either hepatic arterial infusion (HAI) or portal venous infusion (PVI). A dual-balloon vena cava catheter and extracorporeal chemofilter were used to capture and filter hepatic venous blood in experimental animals. Control animals received chemotherapy without hepatic venous isolation and chemofiltration. Following a 5-min HAI of doxorubicin (3 or 5 mg/kg), control and experimental animals had similar doxorubicin levels in their livers and VX-2 tumors, but experimental animals showed a significant reduction in doxorubicin levels in systemic plasma, heart, and kidney tissue as compared with control animals (P < 0.01). HAI produced a 4-fold increase in doxorubicin levels in VX-2 tumors as compared with the drug levels obtained using PVI (P < 0.01). A single HAI of 3 mg/kg doxorubicin in animals treated with CHVI-CF produced marked tumor necrosis at 7 and 14 days after treatment. By increasing the total body clearance of doxorubicin, this system will allow HAI of higher doses of drug in attempts to improve the antitumor response.

Animals↗
PubMed1993

Imaging of colorectal carcinoma with technetium-99m radiolabeled Fab' fragments.

In this phase III study, patients who had previously undergone surgery for colorectal cancer were studied using a technetium-99m (99mTc)-labeled anti CEA antibody (IMMU-4 [Immunomedics, Morris Plains, NJ] 1mg of protein) to evaluate recurrence. Total-body, planar, and single photon emission computed tomography (SPECT) images were performed within 6 hours of injection. Objectives were to evaluate the efficacy of the 99mTc-labeled anti-CEA antibody, to assess sensitivity and specificity of the agent in known lesions, and to detect occult disease. The impact of antibody study on subsequent surgery was also evaluated. The Fab' fragment has a molecular weight of 54,000 and is supplied as a lyophilized kit that can be instantaneously labeled with 20 to 30 mCi of [99mTc]pertechnetate. In 9 patients with known disease, planar spot imaging identified lesions in 7 (78% sensitivity), SPECT imaging detected lesions in 8 (88% sensitivity), and 1 patient did not have SPECT. In the group of 10 patients with occult (or equivocal) disease, planar imaging sensitivity was 50%, and SPECT sensitivity was 100%. Analysis by site showed 14 of 24 lesions detected by planar imaging (58% sensitivity), and SPECT detected 24 of 24 lesions (100% sensitivity). Tumors as small as .5 cm were visualized in the 19 patients studied. The surgeon judged the antibody study to be impact neutral in 73% of the cases and helpful in 27% of the cases when antibody study altered the presurgical plan.

Colorectal Neoplasms↗
PubMed1993

Adjuvant hepatic arterial infusion chemotherapy after curative resection of colorectal liver metastases.

We performed a prospective study of adjuvant hepatic arterial infusion chemotherapy after resection of colorectal liver metastases. We placed hepatic arterial infusion ports in 20 consecutive patients undergoing curative resection of colorectal liver metastases. The chemotherapy regimen was a weekly bolus of 5-fluorouracil (15 mg/kg) for 6 months. The median follow-up has been 33 months. Nine of the 18 evaluable patients (50%) have developed recurrent colorectal cancer. The liver was the only site of failure in 3 of 18 patients (17%), and extrahepatic recurrences occurred in 6 of 18 patients (33%). All patients without recurrence are alive. The median survival of the patients without recurrent disease is 39 months, compared with 27 months for those with recurrent metastatic disease (p < 0.01). In patients who received adjuvant hepatic arterial infusion chemotherapy compared with historical controls treated with surgery alone, we have observed a decreased incidence of recurrent disease after liver resection for metastases. We recommend that patients who undergo hepatic resection for colorectal metastases be considered for postoperative adjuvant chemotherapy to decrease the likelihood of recurrence and to improve survival.

Adult↗
PubMed1993

The detection of breast cancer after augmentation mammaplasty.

Thirty-five patients treated for 37 cases of breast cancer after augmentation mammaplasty were analyzed. All augmentations were performed with silicone gel prostheses at a mean age of 38 years (range 24 to 59 years). The mean interval from breast augmentation to the detection of breast cancer was 7.5 years. Physical examination demonstrated a palpable breast mass in 35 of the 37 cases (95 percent). The pathologic staging was in situ 3 (8 percent), local 18 (49 percent), and nonlocal 16 (43 percent). Standard compression mammography was performed in 31 patients prior to breast biopsy. Abnormalities were detected in 17 (54.8 percent). Palpable masses were visualized in only 12 (38.7 percent). Ultrasound was utilized successfully in 3 patients with palpable masses to guide fine-needle aspiration biopsy. Standard two-view mammography has a low sensitivity in detecting palpable cancers in patients who have undergone augmentation mammaplasty. Ultrasound should be evaluated as a routine adjunctive screening method in this group of patients. The clinical detection of breast cancer, as evidenced by pathologic staging, is not delayed.

Adult↗
PubMed1993

Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer.

Activation of the tyrosine kinase of the c-src gene product, pp60c-src, has been shown to occur in nearly every primary colorectal carcinoma, and is found as early as in polyps of high malignant potential. However, no studies have addressed potential pp60c-src changes which occur during progression. To examine this question, we have studied kinase activity and protein levels in 7 colonic polyps, 19 primary lesions, and 19 liver metastases relative to normal colonic mucosa. Significant increases in tyrosine kinase activity were seen as early as in colonic polyps of high malignant potential. Further increases were observed in activity and level in primary tumors. However, the greatest increases in activity and protein levels were observed in liver metastases. Additionally, six metastatic lesions were obtained in which synchronous primary tumor was resected. In each of these liver metastases, pp60c-src activity and level were significantly increased relative to the corresponding primary tumor, as well as to normal colonic mucosa. Our results demonstrate that progression of colon primary tumors to liver metastases correlates with increased pp60c-src kinase activity and protein level.

Adenocarcinoma↗
PubMed1993

Arterial complications from long-term hepatic artery chemoinfusion catheters: evaluation with CT.

OBJECTIVE: The purpose of this study was to define CT changes in the common hepatic artery and the porta hepatis caused by complications of long-term placement of a catheter in the hepatic artery for infusion of chemotherapeutic agents via a surgically implanted pump or port. MATERIALS AND METHODS: We retrospectively reviewed abdominal CT scans of 115 patients before and after placement of a catheter into a hepatic artery for chemoinfusion, with special attention to the common hepatic artery and the porta hepatis. The changes seen on CT scans were correlated with clinical findings and other imaging findings (arteriography and radionuclide scanning) in patients who had symptoms related to catheters and pumps, including pain during treatment, persistent pain without apparent cause, or occlusion of the catheter. RESULTS: CT scans of 20 patients (17%) showed changes along the common hepatic artery. Five had rounded, low-density fluid collections around the tip of the catheter, believed to be caused by extravasation of chemotherapeutic agents or heparin. Five had well-defined soft-tissue densities along the hepatic artery, where the tip of the catheter was located; these were thought to be caused by dissection of the artery with periarterial fibrosis. Ten had poorly defined areas of low density along the vessel, which may have been caused by periarterial edema, arteritis, or extravasation of the chemotherapeutic agents. Two patients had pain on injection through the device, but no changes were seen on CT scans. Fourteen of 16 patients who had symptoms related to infusion catheters had CT changes in the porta hepatis. CONCLUSION: Fluid collections and soft-tissue densities around the tip of the catheter and along the hepatic artery seen on CT scans of patients who had surgical placement of catheters for chemoinfusion should be recognized as possible complications from the treatment and lead to further study to confirm the diagnosis.

Adult↗
PubMed1993

Pathways of nodal metastasis in carcinomas of the cecum, ascending colon, and transverse colon: CT demonstration.

The distribution of regional lymph node metastases in carcinomas of the cecum, ascending colon, and transverse colon follows the vascular distribution in the ileocolic mesentery, ascending mesocolon, and transverse mesocolon. The location of these metastatic nodes can be recognized on CT scans when the anatomy of the vessels in the ileocolic mesentery and mesocolon is well understood. This knowledge is important in the preoperative staging of carcinomas of the colon for curative surgery and in the early detection of recurrent nodal disease after curative surgery.

Cecal Neoplasms↗
PubMed1993

Locally advanced carcinoma of the colon and rectum involving the urinary bladder.

We reviewed the records of 70 patients who underwent resection of a carcinoma of the colon and rectum with en bloc total cystectomy (36 patients) or partial cystectomy (34 patients) because of tumor directly extending into the urinary bladder. Preoperative genitourinary symptoms were present in 33 of the 70 patients (41.7 percent) and were highly predictive of malignant invasion of the bladder (97.0 percent). Duration of catheter drainage after partial cystectomy correlated with early postoperative bladder function; all 25 patients who had the catheter remain in place at least ten days had normal voiding after catheter removal, while five of nine patients whose catheter was removed before ten days had retention requiring catheter reinsertion (p < 0.01). Urologic complications occurred in two patients after total cystectomy and in three patients after partial cystectomy. There were three postoperative deaths in the total cystectomy group but none after partial cystectomy. Sixty-four patients with negative resection margins had a median survival period of 34 months and a five-year actuarial survival rate of 51.8 percent. In contrast, the median survival period for six patients who had positive margins was 11 months, with no survivors at five years.

Adult↗
PubMed1993

Technical considerations and complications associated with the placement of 180 implantable hepatic arterial infusion devices.

BACKGROUND: Treatment regimens with hepatic arterial chemotherapy infusion are being investigated in an attempt to improve survival and quality of life for patients with primary and metastatic liver malignancies. The successful delivery of chemotherapeutic drugs through an implantable hepatic arterial infusion device depends on the surgeon's understanding of hepatic arterial anatomy, the proper cannulation technique, and the operative measures necessary to prevent misperfusion of drug. METHODS: Between January 1, 1987, and December 31, 1991, we placed implantable hepatic arterial infusion devices in 180 patients. The records of these patients were review to determine (1) the incidence and surgical management of variant hepatic arterial anatomy and (2) the complications associated with surgical placement of these devices. RESULTS: Variant hepatic arterial anatomy requiring ligation of the variant vessel or nonstandard cannulation was seen in 66 patients (36.7%). Treatment response rates and duration of treatment were no different for these 66 patients than for the 114 patients with standard hepatic arterial anatomy (p = 0.94). There were no operative deaths in this series. Operative or early postoperative (within 30 days) complications occurred in 10 patients (5.5%). However, late complications or device-related malfunctions developed in 52 patients (28.8%). CONCLUSIONS: An understanding of regional arterial anatomy is required to surgically place a catheter to achieve bilobar hepatic arterial perfusion and avoid gastroduodenal misperfusion of drug. Placement of hepatic arterial infusion devices has a low rate of early morbidity, but surgeons should be aware of late complications that may develop in patients undergoing hepatic arterial chemotherapy infusion through an implantable device.

Chemotherapy, Cancer, Regional Perfusion↗
PubMed1993

Reduction of systemic drug exposure after hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration.

BACKGROUND: Hepatic arterial infusion of doxorubicin has produced tumor response in hepatic malignancies; however, the limited success of these treatments is related in part to dose-limiting systemic toxicities. The purpose of this study was to determine whether a novel venous isolation-chemofiltration system could limit systemic exposure to doxorubicin after hepatic arterial infusion. METHODS: Doxorubicin (1 or 3 mg/kg) was infused in the hepatic arteries of domestic pigs after complete hepatic venous isolation was achieved with a dual-balloon vena cava catheter. The hepatic vein effluent was pumped through an extracorporeal carbon chemofiltration circuit. Doxorubicin levels were measured in prefilter (hepatic vein), postfilter, and systemic serum at intervals up to 1 hour after drug infusion. RESULTS: Complete hepatic venous isolation with extracorporeal chemofiltration significantly reduced (> 90%) the postfilter and systemic levels of doxorubicin compared with prefilter levels (p < 0.01). At the time animals were killed 7 days after infusion of doxorubicin (3 mg/kg), tissue levels of doxorubicin in the liver showed a 16-fold increase compared with levels in the heart (p < 0.01). CONCLUSIONS: For chemotherapeutic drugs like doxorubicin with a low first-pass extraction by the liver, the novel system described herein achieved significant reduction in systemic drug exposure. This system will allow dose intensification of doxorubicin administered by hepatic arterial infusion to treat hepatic malignancies.

Alanine Transaminase↗
PubMed1992

Sphincter-preserving extended resection for locally advanced rectosigmoid carcinoma involving the urinary bladder.

Radical en bloc resection has gained acceptance in the management of locally advanced colorectal carcinoma. Total pelvic exenteration has been advocated as treatment for rectosigmoid cancers involving adjacent genitourinary structures. We report a series of 10 patients who underwent total cystectomy with en bloc segmental colorectal resection and restoration of intestinal continuity. All margins, including the distal colorectal margin of resection, were pathologically uninvolved by tumor. The median follow-up on these patients was 44 months and the mean survival was 42.5 months. The local recurrence rate (20%) and survival rates are comparable to those in reports describing pelvic exenteration for colorectal cancer. Our patients had normal postoperative bowel function. An extended colorectal resection, including a total cystectomy with rectal sphincter preservation, is occasionally possible when tumor-negative resection margins can be achieved. By restoring intestinal continuity, such an operation provides an improved quality of life, and more importantly, fulfills the criteria for an oncologically sound operation.

Colorectal Neoplasms↗
PubMed1992

Inferior vena cava leiomyosarcoma.

Leiomyosarcoma of the inferior vena cava is a rare malignancy, and radical resection with negative margins remains the only hope for cure. In this report we cite four cases of this tumor treated at The University of Texas M.D. Anderson Cancer Center with particular emphasis on the use of preoperative chemotherapy. In our patients, preoperative chemotherapy did not adversely affect operative outcomes or survival. The potential benefits of preoperative chemotherapy include control of micrometastases, reduction in tumor size before resection, and in situ evaluation of tumor response to chemotherapy for postoperative adjuvant therapy.

Adult↗