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Biomedical subjects

S A Curley

Publications and source records attributed to S A Curley.

90 records · Page 5Linked to original sources
PubMed1992

Murine Kupffer cells and hepatic natural killer cells regulate tumor growth in a quantitative model of colorectal liver metastases.

This investigation aimed to develop a biologically relevant murine model of colorectal liver metastases and determine if Kupffer cells (KC) and hepatic natural killer cells (hNKC) regulate tumor growth. The model involves the injection of murine colon adenocarcinoma 26 (MCA 26) tumor cells into the portal vein of female-specific pathogen-free BALB/c mice. Metastases developed in all animals, and the growth was limited entirely to the liver. To determine if KC and hNKC control the development of liver metastases, the in vivo function of these hepatic effector cells was modulated. Tumor growth was quantitated by the uptake of 125I into tumor DNA. Stimulation of the KC and hNKC produced a significant (P less than 0.01) dose-dependent decrease in 125I uptake in the liver in both treatment groups, which was associated with a significant improvement in survival (P less than 0.05). The in vivo cytotoxic function of the liver was inhibited with an intravenous injection of gadolinium chloride (for KC) or asialo GM1 antiserum (for hNKC). Inhibition of KC and hNKC cytotoxic function led to a significant (P less than 0.01) increase in 125I uptake in the liver and a significant decrease in survival (P less than 0.05).

Adenocarcinoma↗
PubMed1992

Extended resection for locally advanced colorectal carcinoma.

We reviewed the medical records of 101 patients who underwent extended resection for locally advanced colorectal carcinoma between 1965 and 1989. Preoperative symptoms related to the genitourinary system were present in 46 patients. Malignant invasion of genitourinary structures by colorectal carcinoma was found in 43 of these 46 patients (93%). In contrast, 51% of the patients without such symptoms had malignant invasion of contiguous structures. Preoperative intravenous pyelography, computerized tomographic scans, and cystoscopy correctly predicted the presence or absence of malignant invasion in 89%, 83%, and 87% of patients, respectively. Tumor-positive resection margins had a negative impact on survival (mean survival: 11.4 months). The 5-year actuarial survival rate for the patients who underwent a curative extended resection (margins tumor negative) was 54%. A thorough preoperative evaluation can identify a significant number of patients with colorectal cancer extending into adjacent organs and structures. Such evaluation is vital for operative planning and patient preparation, since an appropriate extended resection can produce long-term local control and patient survival.

Adult↗
PubMed1992

Traumatic neuroma of the bile duct causing cholangitis and atrophy of the right hepatic lobe.

Intraluminal traumatic neuromas are an unusual cause of bile duct obstruction. These benign collections of disorganized nerve fibers arise from a bile duct injury during cholecystectomy. Symptoms associated with obstruction or cholangitis may develop decades after the operation. Our patient's neuroma imitated a malignant neoplasm, but the patient has been returned to good health by resection of the right hepatic duct and the atrophic right hepatic lobe.

Aged↗
PubMed1992

Regional lymph node metastases in carcinoma of the left side of the colon and rectum: CT demonstration.

The distribution of regional lymph node metastases in carcinoma of the left side of the colon, rectum, and anus can be well shown by routine CT of the abdomen and pelvis. Recognition of the location of nodes in the mesocolic, left colic, and IMA nodal groups can help in developing a systematic approach to the detection of nodal metastasis. This can be especially important in preoperative planning for cases in which resection may be curative. In addition, an understanding of the distribution of nodal metastasis will make it possible to recognize early recurrent nodal disease, particularly with an increase in associated increase in levels of carcinoembryonic antigen, and to predict certain clinical sequences such as hydronephrosis of the left kidney associated with left colic nodal metastases.

Anus Neoplasms↗
PubMed1991

Hepatic arterial infusion chemotherapy with complete hepatic venous isolation and extracorporeal chemofiltration: a feasibility study of a novel system.

When chemotherapeutic drugs with low liver extraction are used for hepatic arterial infusion (HAI), dosage limits are usually determined by systemic rather than hepatic toxicity. If such agents could be administered by HAI at dosages limited by hepatic toxicity, regional drug exposure and therapeutic efficacy might be significantly enhanced. We report herein a novel system that achieves complete hepatic venous isolation using a dual-balloon vena cava catheter that can be inserted percutaneously. This catheter is connected to a carbon filter in an extracorporeal venous bypass circuit to recover drug that is not absorbed by the liver after HAI. The hemodynamic response to this system was evaluated in six pigs. When the animals were placed on the extracorporeal circuit, we observed a 22% decrease in cardiac output that was well tolerated without significant change in blood pressure. When the filter was incorporated into the circuit, cardiac output was significantly reduced (50%); however, continuous infusion of phenylephrine rapidly normalized blood pressure, heart rate, cardiac output, and left ventricular filling pressures. Initial testing of chemofiltration efficacy was performed in four of the six animals, the remaining two animals being used only to assess hemodynamic response. One each of the four tested animals received either doxorubicin (3 or 9 mg/kg), mitomycin C (1 mg/kg), or cisplatin (1 mg/kg) by HAI. The filter removed over 90% of hepatic venous doxorubicin and mitomycin C and 65% of hepatic venous cisplatin. This feasibility study confirms that hepatic venous isolation with chemofiltration can significantly reduce systemic exposure to high-dose chemotherapeutic agents given by HAI.

Animals↗
PubMed1990

Human Kupffer cells are cytotoxic against human colon adenocarcinoma.

Colorectal liver metastases are a common clinical problem and require more effective therapy. Kupffer cells (KC) perform many important homeostatic functions within the liver and may also possess the ability to mediate tumor cytotoxicity. We investigated the ability of human KC to mediate cytotoxicity against human colon adenocarcinoma targets (HT 29) in vitro. Unstimulated human KC were cytotoxic against the HT 29 targets at all effector/target ratios tested. This cytotoxicity was increased significantly (p less than 0.05) when the KC were stimulated with interferon-gamma and lipopolysaccharide. Human KC produced tumor necrosis factor (TNF), and KC stimulation significantly (p less than 0.05) increased secretion of this monokine. The addition of anti-TNF antibody to the KC-HT 29 cocultures completely neutralized all of the available TNF yet cytotoxicity was not affected, suggesting the participation of a membrane-bound form of TNF or other mechanisms.

Adenocarcinoma↗
PubMed1990

Hepatic artery infusion pumps: cannulation techniques and other surgical considerations.

Long term hepatic artery chemotherapy for metastatic disease to the liver has been made practical by technologic advances in pumps and catheters. The surgical placement of these pumps and catheters can be associated with a significant morbidity unless careful attention is given to variations in hepatic arterial anatomy and to eliminating collateral arterial supply to the distal stomach and duodenum. Gastroduodenal devascularization should be performed in all patients and should be confirmed both with intra-operative fluorescein injection and postoperative scintigraphy scanning. Routine cholecystectomy avoids the complication of chemical cholecystitis. Exact placement of the catheter tip at the junction of the gastroduodenal artery and the hepatic artery with fixation of the catheter in this position by placement of bidirectional ligatures around the catheter bead will reduce the incidence of hepatic artery thrombosis and catheter migration. Intrahepatic arterial collateralization in most patients allows for ligation of variant lobar vessels with total liver perfusion through the remaining lobar arterial supply. This again can be confirmed intra-operatively with fluorescein injection and postoperatively with scintigraphy scanning. Strict attention to these technical details will allow continued use of this important therapeutic modality in the treatment of hepatic metastases and by minimizing surgical complications will encourage continued trials to improve the efficacy of long term hepatic arterial chemotherapy.

Animals↗
PubMed1990

Human recombinant macrophage colony stimulating factor activates murine Kupffer cells to a cytotoxic state.

Activated macrophages mediate cytotoxicity against tumor targets and thus may modulate development and growth of metastatic tumor cells. Macrophage colony stimulating factor (M-CSF) has a potential role in activating mature macrophages to a cytotoxic state. We employed a murine Kupffer cell (KC) model of cytotoxicity against a tumor necrosis factor (TNF) - sensitive murine colon adenocarcinoma cell line (MCA26) to evaluate the ability of recombinant human M-CSF (rhM-CSF) 1) to act alone as a KC-activating agent and 2) to enhance KC cytotoxicity against MCA26 cells in association with known macrophage activating compounds. rhM-CSF produced a dose-dependent increase in TNF release by KC in vitro with a parallel increase in MCA26 killing. KC activated by rhM-CSF produced less TNF and concomitantly demonstrated a lower cytotoxicity against MCA26 cells when compared with KC activated by gamma interferon (gamma IFN) with or without lipopolysaccharide (LPS). M-CSF did not act in a synergistic fashion with gamma IFN and LPS to increase TNF secretion or cytotoxicity against MCA26 cells. rhM-CSF thus acts as a single agent capable of activating murine KC to a cytotoxic state but does not cooperate with classical priming/triggering signals to achieve KC activation.

Animals↗
PubMed1990

Advances in the detection and treatment of colorectal carcinoma.

New technologies and ideas are emerging in the diagnosis, treatment, and follow-up of patients with colorectal carcinoma. The goal of detecting both primary and recurrent disease at an earlier stage remains elusive, but in some cases it may now be attainable. Improvements in surgical technique and instrumentation have led to the utilization of a variety of procedures for treatment, including more conservative operations for colorectal carcinoma detected at an early stage. Active specific immunotherapy using the patient's tumor cells to create a vaccine may improve the rate of survival in a disease for which no adequate adjuvant therapy currently exists. Further basic scientific and clinical research involving diagnostic and treatment modalities for colorectal carcinoma may lead to improved patient survival rates in the future.

Adenocarcinoma↗
PubMed1989

Giant cystic hygroma of the posterior mediastinum.

The case of a 5-year-old girl with a giant cystic hygroma of the posterior mediastinum is reported. Although the tumor was bilateral, it was excised by unilateral thoractomy. The unique anatomical features of this tumor suggested an embryologic origin from the cisterna chyli or the primitive paired thoracic ducts.

Child, Preschool↗
PubMed1989

Surgical therapy of early rectal carcinoma.

Radical surgical resection is the "gold standard" treatment for rectal carcinoma. Results indicating that radiation therapy reduces the incidence of local recurrence and that combined modality radiation therapy and chemotherapy reduce the rate of local and distant failures, as well as improving survival, has produced interest in adjuvant therapy. Conservative procedures to treat rectal cancer are also gaining support because of reduced morbidity and mortality, avoidance of colostomy, and excellent survival figures in selected patients. The key phrase continues to be "in selected patients" because current data support conservative procedures as attempts for cure only in patients with small, histologically favorable tumors. The combination of local excision and adjuvant external beam irradiation holds promise for improved control of local disease in patients with early rectal carcinoma. Further prospective evaluation with long-term follow-up of patients with early rectal carcinoma treated with conservative procedures is needed to assess the efficacy of conservative management.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Analysis of techniques and results in 347 consecutive colon anastomoses.

We have reported our experience with 347 consecutive colon anastomoses in 321 patients seen over an 8 year period. The overall anastomotic failure, mortality, and complication rates were 1.4, 2, and 10 percent, respectively, for the entire series. The complication and death rates were significantly higher in patients whose anastomoses were completed as part of an emergency procedure. Even though various one- and two-layer inverting techniques, suture materials, and staples were used, we could not identify any one method as being clearly superior in preventing anastomotic complications, although the results do suggest that some caution may be appropriate before mechanical stapling devices are universally applied. The results support that adherence to accepted surgical principles of reducing the solid content and fecal flora of the colon prior to operation, insuring an excellent blood supply to both bowel ends, even approximation of the bowel ends with inverting sutures which include the submucosal layer of the bowel, absence of tension, meticulous hemostasis, and avoidance of anastomosis in the presence of peritonitis are the primary means of avoiding dehiscence of colon anastomoses.

Adolescent↗
PubMed1988

Traumatic disruption of the subclavian artery and brachial plexus in a patient with Ehlers-Danlos syndrome.

A 17-year-old girl with Ehlers-Danlos syndrome underwent simple reduction of a dislocated shoulder that was complicated by disruption of the subclavian artery and brachial plexus. The shoulder dislocation was a recurrent condition that had been treated successfully on several previous occasions without complication. During the relocation process, only minor upper extremity manipulation caused injury to the brachial plexus and subclavian artery. Management of an iatrogenic vascular injury was made difficult by the fragile consistency of the anterial wall that would not hold sutures. Amputation of the patient's arm ultimately was required.

Adolescent↗
PubMed1987

Late complications after gastric reservoir reduction with external wrap.

Numerous surgical procedures have been introduced to facilitate weight loss in morbidly obese individuals. Gastric reservoir reduction, wrapping the stomach with an inert fabric, is one such procedure. Nissen fundoplication has been performed in conjunction with this approach to prevent postoperative gastroesophageal reflux. Gastric perforation and functional gastroesophageal obstruction occurring as late as 71 months after this operation represent late complications. Perforation has developed in 14.6% of stomachs wrapped with polypropylene mesh. Nissen fundoplication may contribute to this complication.

Adult↗
PubMedDate not supplied

Overexpression of focal adhesion kinase (p125FAK) in human colorectal carcinoma liver metastases: independence from c-src or c-yes activation.

BACKGROUND: p125FAK, pp60C-src, and pp62c-yes are protein tyrosine kinases that function in signaling pathways regulating cell adhesion, migration, and growth. The expression and tyrosine kinase activities of pp60c-src and pp62c-yes, and the expression of p125FAK are increased in colorectal tumor metastases relative to normal mucosa. This study investigates whether differences in the activation of pp60c-src and pp62c-yes in colorectal liver metastases correlated with differences in p125FAK expression and whether prognostic significance could be demonstrated from the extent of expression of p125FAK in metastases. METHODS: Activities of pp60c-src and pp62c-yes were measured in the immune complex kinase assay. Relative levels of p125FAK, pp60c-src, and pp62c-yes were determined by immunoblotting. RESULTS: p125FAK was overexpressed in 29 of 30 colorectal cancer liver metastases (range of two-to 195-fold increase compared with normal mucosa). The degree of overexpression of p125FAK was not a significant prognostic factor in survival. A differential activation of pp60c-src and pp62c-yes in colorectal carcinoma liver metastases was observed. However, overexpression of p125FAK was observed in metastases with either pp60c-src or pp62c-yes activated in colorectal carcinoma liver metastases. CONCLUSIONS: p125FAK overexpression appears to be a marker present in colorectal cancer cells with a metastatic phenotype. Furthermore, p125FAK overexpression is independent of pp60c-src or pp62c-yes activation in human colorectal carcinoma liver metastases.

Biomarkers, Tumor↗
PubMedDate not supplied

Hepatitis B or C virus serology as a prognostic factor in patients with hepatocellular carcinoma.

It is not clear whether chronic hepatitis B or C virus (HBV or HCV) infection is a prognostic factor for hepatocellular carcinoma. We performed this study to determine if chronic HBV or HCV infection had any impact on postresection survival or affected patterns of failure. The records of 77 patients undergoing surgical resection for hepatocellular carcinoma between January 1990 and December 1998 were reviewed. Forty-four patients (57%) had HCV infection, 18 patients (23%) had HBV infection, and 15 patients (20%) had negative serology. There were no differences in age, sex, or tumor size among the groups, and all patients had margin-negative resections. There was a significantly higher incidence of satellitosis and vascular invasion in patients with HCV infection (32% and 41% respectively; P <0.05 vs. other groups). With a median follow-up of 30 months, a significantly decreased local disease-free survival (LDFS) was seen in HBV-positive (5-year LDFS 26%) or HCV-positive (5-year LDFS 38%) patients compared to those with negative serology (5-year LDFS 79%; P <0.05). There was also a trend toward a decreased overall survival in patients with positive hepatitis serology compared to patients with negative serology (37% vs. 79%; P = 0.12). Univariate analysis revealed that only satellitosis was related to local recurrence and overall survival. Patients with positive serology for hepatitis B or C undergoing resection for hepatocellular carcinoma have a trend toward worse overall prognosis and a significantly decreased LDFS when compared to patients with negative serology.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

New trends in the surgical treatment of colorectal cancer liver metastases.

Colorectal cancer is one of the most common solid tumors affecting people around the world. A significant proportion of patients with colorectal cancer will develop or will present with liver metastases. In some of these patients, the liver is the only site of metastatic disease. Thus, surgical treatment approaches are an appropriate and important treatment option in patients with liver-only colorectal cancer metastases. Resection of colorectal cancer liver metastases can produce long-term survival in selected patients, but the efficacy of liver resection as a solitary treatment is limited by two factors. First, a minority of patients with liver metastases have resectable disease. Second, the majority of patients who undergo successful liver resection for colorectal cancer metastases develop recurrent disease in the liver, extrahepatic sites, or both. In this paper, in addition to the results of liver resection for colorectal cancer metastases, we will review the results of cryoablation, heat ablation, and hepatic arterial chemotherapy using a surgically implanted pump. Each of these surgical treatment modalities can produce long-term survival in a subset of patients with liver-only colorectal cancer metastases, whereas systemic chemotherapy used alone rarely results in long-term survival in these patients. While surgical treatments provide the best chance for long-term survival or, in some cases, the best palliation in patients with colorectal cancer liver metastases, it is clear that further improvements in patient outcome will require multimodality therapy regimens.

Antineoplastic Agents↗