Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer.

PURPOSE: To determine the safety and tolerability of adenovirus-mediated p53 (Adp53) gene transfer in sequence with cisplatin when given by intratumor injection in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC and abnormal p53 function were enrolled onto cohorts receiving escalating dose levels of Adp53 (1 x 10(6) to 1 x 10(11) plaque-forming units [PFU]). Patients were administered intravenous cisplatin 80 mg/m(2) on day 1 and study vector on day 4 for a total of up to six courses (28 days per course). Apoptosis was determined by the terminal deoxynucleotidyl- transferase-dUTP nick-end labeling assay. Evidence of vector-specific sequences were determined using reverse-transcriptase polymerase chain reaction. Vector dissemination and biodistribution was monitored using a series of assays (cytopathic effects assay, Ad5 hexon enzyme-linked immunosorbent assay, vector-specific polymerase chain reaction assay, and antibody response assay). RESULTS: Twenty-four patients (median age, 64 years) received a total of 83 intratumor injections with Adp53. The maximum dose administered was 1 x 10(11) PFU per dose. Transient fever related to Adp53 injection developed in eight of 24 patients. Seventeen patients achieved a best clinical response of stable disease, two patients achieved a partial response, four patients had progressive disease, and one patient was not assessable. A mean apoptotic index between baseline and follow-up measurements increased from 0.010 to 0.044 (P =.011). Intratumor transgene mRNA was identified in 43% of assessable patients. CONCLUSION: Intratumoral injection with Adp53 in combination with cisplatin is well tolerated, and there is evidence of clinical activity.

Selective hepatic arterial chemoembolization for liver metastases in patients with carcinoid tumor or islet cell carcinoma.

In many patients with liver metastases from islet cell or carcinoid tumor, vascular occlusion therapy results in prolonged control of symptoms, biochemical response, and also tumor regression. Chemotherapy agents were added to evaluate safety and efficacy. Thirty patients with liver metastases from either carcinoid tumor or islet cell carcinoma underwent sequential vascular occlusion therapy combined with chemotherapeutic agents. In patients with carcinoid tumor, a combination of cisplatin (150 mg) and doxorubicin (50 mg) was used. In patients with islet cell carcinoma, a combination of 5-fluorouracil (350 mg) and streptozotocin (1000-2000 mg) was used. Sixteen patients had carcinoid tumor and 14 had islet cell carcinoma. Biochemical response was observed in 12 of 16 (75%) carcinoid patients and 9 of 10 (90%) islet cell patients. The overall partial response rate was 37% (11/30 patients). Partial response occurred in 4 of 16 (25%) patients with carcinoid tumor and 7 of 14 (50%) with islet cell carcinoma. The median duration of partial responses was 24 months (range, 6-63+ months). The median survival of all patients was 15 months (range, 2-67+ months). No treatment-related deaths occurred. Our data suggest that the addition of these chemotherapeutic agents to vascular occlusion, although safe, has no additional benefit.

Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer.

BACKGROUND: Preclinical studies in animal models have demonstrated tumor regression following intratumoral administration of an adenovirus vector containing wild-type p53 complementary DNA (Ad-p53). Therefore, in a phase I clinical trial, we administered Ad-p53 to 28 patients with non-small-cell lung cancer (NSCLC) whose cancers had progressed on conventional treatments. METHODS: Patients received up to six, monthly intratumoral injections of Ad-p53 by use of computed tomography-guided percutaneous fine-needle injection (23 patients) or bronchoscopy (five patients). The doses ranged from 10(6) plaque-forming units (PFU) to 10(11) PFU. RESULTS: Polymerase chain reaction (PCR) analysis showed the presence of adenovirus vector DNA in 18 (86%) of 21 patients with evaluable posttreatment biopsy specimens; vector-specific p53 messenger RNA was detected by means of reverse transcription-PCR analysis in 12 (46%) of 26 patients. Apoptosis (programmed cell death) was demonstrated by increased terminal deoxynucleotide transferase-mediated biotin uridine triphosphate nick-end labeling (TUNEL) staining in posttreatment biopsy specimens from 11 patients. Vector-related toxicity was minimal (National Cancer Institute's Common Toxicity Criteria: grade 3 = one patient; grade 4 = no patients) in 84 courses of treatment, despite repeated injections (up to six) in 23 patients. Therapeutic activity in 25 evaluable patients included partial responses in two patients (8%) and disease stabilization (range, 2-14 months) in 16 patients (64%); the remaining seven patients (28%) exhibited disease progression. CONCLUSIONS: Repeated intratumoral injections of Ad-p53 appear to be well tolerated, result in transgene expression of wild-type p53, and seem to mediate antitumor activity in a subset of patients with advanced NSCLC.

Outpatient management of pneumothorax after fine-needle aspiration: economic advantages for the hospital and patient.

PURPOSE: To evaluate the efficacy and cost savings of outpatient management of post-fine-needle aspiration (FNA) pneumothoraces with small-caliber catheters. MATERIALS AND METHODS: The authors retrospectively reviewed the medical and hospital billing records from 74 patients with enlarging or symptomatic post-FNA pneumothoraces treated with a small-caliber catheter. Forty patients (54%) were treated on an outpatient basis, 17 patients (23%) were treated on an inpatient basis, and 17 patients (23%) were monitored overnight in the emergency department. Only one patient initially treated on an outpatient basis had to return for inpatient observation and suction because of a persistent pneumothorax. RESULTS: The catheters remained in place overnight in 46 patients (33 outpatients, 12 emergency department patients, and one inpatient). The number of days the catheters were left in place was prolonged (range, 2-13 days) in seven outpatients, five emergency department patients, and 16 inpatients. The mean cost per patient for lung biopsy and pneumothorax management was as follows: outpatients, $1,689; emergency department patients, $2,403; and inpatients, $3,950. Elevated inpatient expense was related to the number of chest radiographs obtained, pharmacy charges, and room charges. Cost elevation for emergency department patients was related to pharmacy charges and the cost of overnight observation. CONCLUSION: Outpatient management of simple pneumothoraces with placement of small-caliber catheters attached to one-way chest drain valves proved to be safe, efficient, and economical.

A large lumen microcatheter for oncologic intervention.

A newly available Tracker-325 catheter (Target Therapeutics, Fremont, CA, USA), modified from the Tracker-18 catheter, has the same outer diameter but a larger lumen. This catheter was used in 15 patients during a 7-month period for superselective arterial catheterization when conventional catheters could not be placed successfully. Arterial embolization (n = 7), chemoembolization (n = 5), and chemoinfusion (n = 3), were performed. The increased luminal diameter of the Tracker-325 allowed an increased flow rate for diagnostic arteriography, accommodated larger embolic particles, and improved the ability to achieve a super-selective position.

An anatomical study of the tarsal tunnel using low pressure compartmental infusion.

The anatomy of the tarsal tunnel is demonstrated using a low-pressure compartmental infusion technique. This is done by infusing colored radiopaque contrast material into three fresh cadaveric specimens. Thin section photography and computed tomography are then used to identify the boundaries and contents of the tarsal tunnel as it traverses the ankle, hindfoot, and midfoot. The tarsal tunnel is shown to communicate proximally with the deep posterior compartment of the leg and distally with the intermediate compartment of the forefoot. The relationships of the structures contained within the tarsal tunnel are shown in detail.

Transosseous air contrast CT-guided needle biopsy of a cystic neoplasm.

CT-guided fine-needle aspiration biopsy of a metastasis from an ovarian cystadenocarcinoma was performed using air contrast and a transosseous approach. Air contrast allowed identification of a papillary projection within the cyst, and the transosseous approach permitted direct and easy access to the lesion.

Intraperitoneal catheters: percutaneous placement with fluoroscopic guidance.

PURPOSE: The authors reviewed their experience with percutaneous placement of catheters into the peritoneal cavity for the administration of intraperitoneal chemotherapy to determine if their approach resulted in a lower complication rate than the reported 12%-16% rate and to demonstrate the technical advantages over surgically placed catheters. PATIENTS AND METHODS: Seventy-six patients with gastrointestinal or gynecologic malignancies underwent 152 procedures during a 20-month period. The catheters were used to deliver antineoplastic agents and, in some patients, to drain ascites. Catheter insertion was performed with local anesthesia and a modified Seldinger technique. A 5-F catheter was used in 89% of procedures; in the remainder, the catheter was of a larger caliber. RESULTS: The procedure was successful in 145 (95%) instances and failed in seven (5%) attempts because of peritoneal adhesions. The catheters remained in place for less than 2 days in 56%, 2-10 days in 25%, and more than 10 days in 19% of patients. One catheter remained in place for 15 weeks. Complications occurred in seven procedures (5%). Four cases of mild peritonitis responded to a brief course of intravenously administered antibiotics, and severe pain in two patients required premature catheter removal. A single case of inadvertent transcolonic catheter placement occurred without adverse sequelae to the patient. CONCLUSIONS: Intraperitoneal catheterization can be performed with local anesthesia by using a simple technique with a very low complication rate. The catheters can remain in place for prolonged periods without significant risks.

CT appearance of the distended trochanteric bursa.

The CT appearance of the distended trochanteric bursa noted in an asymptomatic patient is reported. The bursal distension was noted incidentally in a patient undergoing staging for renal cell carcinoma. On CT the distended bursa was noted as a septated low attenuation lesion at the site of insertion of the gluteus medius and minimus muscles on the greater trochanter of the femur. The lesion was not associated with any degenerative changes in the hip or greater trochanter. Distension of the trochanteric bursa may occur in asymptomatic patients and the appearance of the distended bursa must be recognized on imaging studies to avoid confusing it with other lesions.

MR appearance of the distended iliopsoas bursa.

The purpose of this essay is to illustrate the MR appearance of the distended iliopsoas bursa. The bursa must be recognized on MR scans to avoid confusing it with malignant neoplasms and other lesions.

MDA-image: an environment of networked desktop computers for teleradiology/pathology.

MDA-Image, a project of The University of Texas M. D. Anderson Cancer Center, is an environment of networked desktop computers for teleradiology/pathology. Radiographic film is digitized with a film scanner and histopathologic slides are digitized using a red, green, and blue (RGB) video camera connected to a microscope. Digitized images are stored on a data server connected to the institution's computer communication network (Ethernet) and can be displayed from authorized desktop computers connected to Ethernet. Images are digitized for cases presented at the Bone Tumor Management Conference, a multidisciplinary conference in which treatment options are discussed among clinicians, surgeons, radiologists, pathologists, radiotherapists, and medical oncologists. These radiographic and histologic images are shown on a large screen computer monitor during the conference. They are available for later review for follow-up or representation.

Open-floored concave compensating filter for angiography.

An open-floored concave compensating filter was designed that produced a radiograph of uniform density, caused no artifacts due to its shape or position, and required little or no increase in exposure in most applications. Selective celiac, hepatic, shoulder, and pelvic angiography was performed with use of the filter; image quality was noticeably improved.

Percutaneous skeletal biopsy.

Percutaneous bone biopsy has become an accepted means for tissue diagnosis in indeterminate metastatic disease, whereas needle biopsy for the evaluation of primary skeletal neoplasms is controversial. Needle biopsies are also of value in the diagnosis of inflammatory lesions and eosinophilic granuloma. The diagnostic accuracy of this procedure ranges from 50 to 94% in malignant disease, but is less favorable in benign disease. The low complication rate of about 0.2% makes the percutaneous approach an attractive alternative to surgical biopsy.

Fine needle aspiration biopsy in lymphoma.

Patients with lymphoma undergo excisional biopsy of an affected lymph node for initial classification of their disease because accurate classification depends on the histologic characteristics of the neoplasm. However, fine needle aspiration cytology has a role in the management of lymphoma patients, particularly in those with recurrent or residual masses following treatment. Moreover, immunologic markers, nucleic acid flow cytometry, cytogenetics, and molecular genetics, which do not depend on histologic characteristics and can be performed on fine needle aspirates, are acquiring more importance in the management of patients with these diseases, particularly in those with non-Hodgkin's lymphoma. These latter tests add objectivity to the cytologic diagnosis of the B-cell lymphomas and increase its accuracy. In most series, the accuracy of fine needle aspiration in patients with lymphoma approaches 90%, with minimal complication rates.

Hepatic artery infusion and chemoembolization in the management of liver metastases.

Hepatic metastases rather than the primary neoplasm usually dictate the course of the disease and patient's survival. For unresectable disease, intraarterial infusion of chemotherapy, embolization, and chemoembolization are viable alternatives. Intraarterial therapy for hepatic metastases is based on the dual blood supply of the normal liver (portal vein, 75%, and hepatic artery, 25%) and that of the tumors (hepatic artery, 90%). Intraarterial infusion delivers a higher concentration of chemotherapy, whereas chemoembolization adds ischemia and increased contact time with the tumor. Selective vascular occlusion for infusion, redistribution of the blood supply and pulsatile flow enhance the delivery of therapeutic agents to the liver.

Percutaneous drainage and feeding gastrostomies in 100 patients.

Percutaneous gastrostomy was performed in 100 cancer patients. In 67 patients with bowel obstruction, the procedure was performed for gastric drainage with 24-28-F Malecot catheters inserted in one sitting. The remaining 33 patients had supragastric obstructions or fistulas and required 10-14-F pigtail catheters for feeding purposes. Average postgastrostomy hospitalization was 3.6 days. Drainage gastrostomies were ready for use immediately after the procedure, whereas use of feeding gastrostomies started on average within 2 days of tube insertion. There were no major complications or deaths related to the procedure. Percutaneous gastrostomy is a simple and safe procedure even when large-caliber catheters are used, and it does not require gastric fixation to the abdominal wall to prevent spillage into the peritoneum.

Gastrointestinal and pancreatic endocrine tumours.

The radiological diagnosis and interventional management of neuroendocrine tumours of the gastrointestinal tract and pancreas are challenging, demanding the complete gamut of available resources. Carcinoid tumours are most commonly found in the appendix and small bowel. Barium studies usually disclose a small solitary mucosal or submucosal mass in the distal ileum at times associated with smooth muscle hypertrophy and thickening of the mucosal folds. Intussusception and bowel obstruction may be the presenting finding. Mesenteric involvement may evoke a desmoplastic reaction with rigidity, fixation, angulation and tethering of small bowel loops. Angiography may demonstrate a hypervascular primary neoplasm but more frequently reveals vascular encasement and distortion from the mesenteric desmoplastic reaction. Pancreatic islet cell tumour is best defined radiologically by angiography and computed tomography as a well circumscribed hypervascular mass which enhances with contrast material. Portal venous sampling is of considerable assistance in localizing insulinoma. Metastases from neuroendocrine tumours to lymph nodes and to the liver are usually hypervascular. In the evaluation of the liver by CT scanning prior to contrast as well as dynamic scanning during the bolus intravenous injection of contrast material are necessary. At times the precontrast scan is more revealing. Computed tomography with the catheter in the superior mesenteric artery followed by selective hepatic arteriography is the most accurate combination for the detection of hepatic metastases. Interventional radiological management by sequential hepatic arterial embolization is the treatment of choice for multiple hepatic metastases from neuroendocrine tumours. Thus far, the maximum number of embolic episodes in a single patient has been 13. The carcinoid syndrome has been controlled in 87% while 79% of islet cell tumour hepatic metastases have responded. Contraindications to HAE includes a combination of all of the following: (i) replacement of more than 50% of the liver by tumour, (ii) serum lactic dehydrogenase above 425 mU/ml, (iii) serum glutamic oxaloacetic transaminase above 100 mU/ml, and (iv) bilirubin above 2 mg/dl. In the face of occlusion of the portal vein by intravascular neoplasm, HAE is contraindicated only if portal flow through collateral vein is away from the liver.