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A Rozenblit

Publications and source records attributed to A Rozenblit.

At least 19 recordsLinked to original sources

Endoleaks after endovascular graft treatment of aortic aneurysms: classification, risk factors, and outcome.

PURPOSE: Incomplete endovascular graft exclusion of an abdominal aortic aneurysm results in an endoleak. To better understand the pathogenesis, significance, and fate of endoleaks, we analyzed our experience with endovascular aneurysm repair. METHODS: Between November 1992 and May 1997, 47 aneurysms were treated. In a phase I study, patients received either an endovascular aortoaortic graft (11) or an aortoiliac, femorofemoral graft (8). In phase II, procedures and grafts were modified to include aortofemoral, femorofemoral grafts (28) that were inserted with juxtarenal proximal stents, sutured endovascular distal anastomoses within the femoral artery, and hypogastric artery coil embolization. Endoleaks were detected by arteriogram, computed tomographic scan, or duplex ultrasound. Classification systems to describe anatomic, chronologic, and physiologic endoleak features were developed, and aortic characteristics were correlated with endoleak incidence. RESULTS: Endoleaks were discovered in 11 phase I patients (58%) and only six phase II patients (21%; p < 0.05). Aneurysm neck lengths 2 cm or less increased the incidence of endoleaks (p < 0.05). Although not significant, aneurysms with patent side branches or severe neck calcification had a higher rate of endoleaks than those without these features (47% vs 29% and 57% vs 33%, respectively), and patients with iliac artery occlusive disease had a lower rate of endoleaks than those without occlusive disease (18% vs 42%). Endoleak classifications revealed that most endoleaks were immediate, without outflow, and persistent (71% each), proximal (59%), and had aortic inflow (88%). One patient with a persistent endoleak had aneurysm rupture and died. CONCLUSIONS: Endoleaks complicate a significant number of endovascular abdominal aortic aneurysm repairs and may permit aneurysm growth and rupture. The type of graft used, the technique of graft insertion, and aortic anatomic features all affect the rate of endoleaks. Anatomic, chronologic, and physiologic classifications can facilitate endoleak reporting and improve understanding of their pathogenesis, significance, and fate.

Aged

Imaging of the vascular system for endovascular grafting and other procedures.

Success of endovascular therapy largely depends on accurate imaging before, during, and after the procedure. The vascular system can be evaluated noninvasively with computed tomography (CT), magnetic resonance (MR) imaging, and duplex ultrasound (US), or invasively with angiography and intravascular ultrasonography (IVUS). Noninvasive methods are preferred for both preprocedure screening and postprocedure follow-up, whereas invasive imaging modalities constitute an essential part of the endovascular procedure. Invasive techniques are also used in preprocedural or postprocedural evaluation when noninvasive methods are unable to obtain important diagnostic information, or when the confirmation of noninvasive imaging findings is desired. Specific roles of these modalities for endovascular treatment of aortoiliac aneurysms are discussed.

Angiography

Endoluminal therapy with endovascular grafts.

The addition of balloon-expandable stents to conventional graft material allows minimally invasive repair of aortic and other aneurysms, arterial occlusions, and arterial trauma. Vascular access can be made at a site far from the pathology.

Aneurysm

Phase I trial of high-dose infusional hydroxyurea, high-dose infusional 5-fluorouracil and recombinant interferon-alpha-2a in patients with advanced malignancies.

The ribonucleotide reductase inhibitor, hydroxyurea (HU), augments the cytotoxic effects of 5-fluorouracil (5FU) in vitro; both drugs are synergistic with interferon-alpha (IFN) in vitro. The aim of this phase I study was to determine the maximal duration of HU, 4.3 g/m2, administered as a parenteral infusion in combination with 5FU, 2.6 g/m2 administered over 24 hrs each week, + IFN, 9 MU, subcutaneously three times per week. There were 26 patients enrolled and evaluable. This included 14 patients with colorectal cancer of whom 13 had been previously treated, and 12 patients with other refractory malignancies (pancreas, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, and others), of whom 10 were previously untreated. The dose-limiting toxicity of this regimen was myelosuppression. This prohibited dose escalation of HU above the starting dose (24 hrs) on a 6-weeks-on, 2-weeks-off therapy schedule. When filgrastim, 480 microg, was administered subcutaneously on days 3-6, the duration of HU could be extended to 48 hrs on a 2-weeks-on, 1-week-off therapy schedule. There were two instances of fatal infection, one in a patient with a rectovaginal fistula with neutropenic sepsis and the second in a patient with non-neutropenic Clostridium septicum sepsis. All therapy was administered in the ambulatory setting. There were three responders, all among previously untreated patients. High-dose parenteral hydroxyurea, 4.3 g/m2 administered over 24 hrs, can be safely combined with high-dose weekly 5FU, 2.6 g/m2 over 24 hrs + IFN, 9 MU subcutaneously three times per week, without filgrastim in the ambulatory setting. Parenteral hydroxyurea, 4.3 g/m2 over 24 hrs daily x 2 can also be combined with high-dose 5FU + IFN, but requires the addition of filgrastim to avoid severe myelosuppression.

Adult

Phase II trial of N-(phosphonacetyl)-L-aspartate (PALA), 5-fluorouracil and recombinant interferon-alpha-2b in patients with advanced gastric carcinoma.

The aspartate transcarbamoylase inhibitor, N-(phosphonacetyl)-L-aspartate (PALA), synergistically enhanced the cytotoxicity of a combination of 5-fluorouracil (5-FU) and interferon-alpha (IFN) against human colon cancer cell lines in vitro. To test the efficacy of this combination in the clinical setting, patients with locally advanced or advanced gastric carcinoma were treated with the combination of PALA, 5-FU and IFN (PFI). Patients were required to have biopsy-proven disease beyond the scope of surgical resection, measurable disease, no prior chemotherapy, adequate bone marrow, renal and hepatic function, to be fully ambulatory and to have given informed consent. Drug was administered as follows: PALA, 250 mg/m2, 15 min i.v. infusion, days 1, 15, 22, 29, and then weekly; 5-FU, 750 mg/m2 daily x 5 as a continuous i.v. infusion beginning day 2, then at 750 mg/m2 days 16, 23 and 30, then weekly; IFN, 9 MU subcutaneously three times per week beginning day 2. There were 22 patients enrolled. The major toxicities were fatigue and associated neurotoxicity, with acceptable gastrointestinal and haematological toxicities. There was one complete responder (5%) and 3 partial responders (14%); two of these responses were durable (> 3 years). Despite this modest clinical activity, other regimens for advanced gastric cancer such as FAMTX and ELF appear to have greater activity with comparable toxicity.

Adenocarcinoma

Cystic adrenal lesions: CT features.

PURPOSE: To define computed tomographic (CT) features of cystic adrenal lesions that differentiate them from similar-appearing adenoma. MATERIALS AND METHODS: CT scans of 13 cystic adrenal lesions (four endothelial cysts, three benign pseudocysts, one nonspecific benign cyst, one carcinoma, one pheochromocytoma, and three stable lesions with no histologic diagnosis) were analyzed retrospectively. Reports in the literature of 26 benign adrenal cysts were also reviewed. RESULTS: Mean lesion diameter was 6.2 cm, and six lesions were less than 5.0 cm. Mean attenuation values was 21 HU, and in eight cases it was less than 15 HU. Partial adrenal involvement was noted in six cases. Ten lesions contained wall or septal calcification. Wall thickness was 3 mm or less in nine and exceeded 6 mm in three lesions; one of the latter was cystic carcinoma. Wall enhancement (but no intralesional enhancement) was found in two of six lesions. Of 37 reviewed benign cysts, 19 had mural and seven had central calcification, 28 were unilocular, and seven had high attenuation value. Wall thickness was 3 mm or less in 31 lesions. CONCLUSION: CT findings of a nonenhancing mass with or without wall calcification allow differentiation of adrenal cyst from adenoma. A small adrenal cyst with near-water attenuation and a thin (< or = 3-mm) wall is likely to be benign.

Adenoma

Phase II trial of chemotherapy, external and intraluminal radiation plus surgery for oesophageal cancer.

A pilot study was performed to assess the feasibility of combining 5-fluorouracil, recombinant alpha-2b-interferon, external radiation therapy and intraluminal high dose rate brachytherapy with surgery in patients with locally advanced esophageal carcinoma. 5-fluorouracil, 750 mg m-2, was administered via continuous 5-day infusion beginning day 1 and weekly thereafter; interferon, 10 mu subcutaneously, was administered three times per week beginning day 1 and sargramostin, 5 micrograms kg-1, was administered on days without 5-fluorouracil. External radiation began on day one using 1.5 daily fractions to 55.5 Gy. Intraluminal brachytherapy was delivered concomitantly once each week for 5 fractions of 4 Gy. None of the first eight patients went to surgery. The external radiation was changed to 1.5 Gy BID to 45 Gy followed by BID intraluminal radiation to 15 Gy. Of the last four patients, there was one case of radiation myelitis. It was found that successful surgery was not possible and excessive toxicities, including radiation myelitis, occurred with this aggressive regimen.

Aged

Audiological findings in a Phase I protocol investigating the effect of WR 2721, high-dose cisplatin and radiation therapy in patients with locally advanced cervical carcinoma.

WR 2721 (ethiofos) protects against the toxic effects of the heavy metal compound cisplatin, which is used in the treatment of solid tumours. In a Phase I protocol designed to determine the maximum dose of WR 2721 which could be tolerated when administered in combination with cisplatin and radiation therapy to patients with cervical carcinoma, 11 patients were evaluated by audiologic testing before and after cisplatin WR 2721 administration in an attempt to identify the degree of ototoxicity. Forty-five per cent were noted to have significant hearing threshold changes, predominantly in the high frequencies. There were no significant changes in the speech frequencies in this series. This contrasts with the greater degrees of ototoxicity observed in controls treated in the same way who received cisplatin without WR 2721 protection.

Amifostine

Endovascular repair of abdominal aortic aneurysm: value of postoperative follow-up with helical CT.

OBJECTIVE: Transfemorally placed endoluminal grafts are currently being evaluated as an alternative to open surgery for the treatment of abdominal aortic aneurysms. We determined the value of helical CT for the follow-up of patients treated with this new procedure. The purposes of this study were to determine CT features of a technically successful procedure, detect complications, and compare findings on CT scans obtained 24-48 hr after insertion of the graft with findings on angiograms obtained at the end of the endovascular procedure. SUBJECTS AND METHODS: Seven patients with large abdominal aortic aneurysms had helical CT within 48 hr after transfemoral insertion of an endoluminal graft. Findings on these CT scans were compared with findings on digital completion angiograms obtained immediately after placement of the graft. Additional follow-up CT scans were obtained for up to 15 months (mean, 8 months). The size of the aneurysmal sac; completeness of perigraft thrombosis; and position, shape, and patency of the device were recorded. RESULTS: CT scans obtained 24-48 hr after placement of the grafts showed complete thrombosis of the aneurysmal sac in three patients and incomplete thrombosis with patent perigraft channels in the four remaining patients. Angiograms showed a patent perigraft channel in only one patient. Two of four initially patent channels subsequently closed, but one of them recurred. Of four thrombosed aneurysms, two decreased in size, and two were unchanged on later follow-up. Of three aneurysms associated with perigraft channels, two became enlarged and one was stable. On the basis of CT criteria, successful endovascular repair was shown in four (57%) of seven patients. CONCLUSION: Helical CT is a sensitive means of evaluating the efficacy of endoluminal grafts. Decreased or stable size of the aneurysmal sac without perigraft channels on late follow-up CT signifies technical success. Persistence or recurrence of perigraft channels is the most likely cause of later enlargement of an aneurysm and therefore suggests procedural failure. Helical CT was more sensitive than angiography for detection of perigraft channels that occurred soon after treatment.

Aged

Utility of embolization or chemoembolization as second-line treatment in patients with advanced or recurrent colorectal carcinoma.

BACKGROUND: Second-line therapy of patients with colorectal cancer metastatic to the liver is unsatisfactory. One alternative to systemic treatment is therapy directed locoregionally. METHODS: Twenty-four patients with unresectable colorectal cancer with bulky liver metastases who had failed prior systemic therapy were randomized to treatment with either embolization or chemoembolization. For the embolization group, particulate transcatheter polyvinyl alcohol (PVA) (150-250-microns particles) mixed with full-strength iodinated radiographic contrast was administered under direct fluoroscopic control. In patients randomized to chemoembolization, 5-fluorouracil (750 mg/m2) and recombinant alpha-2a-interferon (Roche Laboratories, Nutley, NJ) (9-MU) were thoroughly mixed into the PVA contrast suspension. Study end points were response to therapy and survival. RESULTS: Of 24 patients, 13 were randomized to chemoembolization and 11 to embolization therapy. All were assessable for toxicity, response, and complications. Among the first 13 patients treated initially, a suppurative abscess developed in one patient, who died. Eleven subsequent patients were pretreated with oral and intravenous antibiotics without further infectious complications. Five patients had hemorrhagic complications, two of which were serious. The treatment was otherwise well tolerated, with most patients experiencing transient pain, fevers, and elevations in leukocyte counts and liver enzymes, which resolved spontaneously. Computed tomography scans of the liver were used to assess patient response to therapy. There were 6 responders (25%) among the 24 patients treated. No differences in response to treatment or survival between the embolization and chemoembolization groups were noted. With a median follow-up of more than 12 months, the median survival was 9.3 months from the time of embolization therapy. CONCLUSIONS: Embolization and chemoembolization therapy appear to have antitumor activity as second-line therapy in patients with colorectal carcinoma with bulky liver metastases. Although generally well tolerated, complications of this therapy may be severe. The addition of further patients to this trial will allow a rigorous comparison of embolization alone versus embolization with chemotherapy.

Adult

Phase II trial of echinomycin in patients with advanced or recurrent colorectal cancer.

Echinomycin is a novel bifunctional intercalating agent derived from Streptomyces echinatus. A phase II clinical trial of echinomycin in patients with advanced, measurable colorectal cancer was initiated to determine the efficacy and toxicities of this agent. Echinomycin, 1.5 mg/m2, was given initially as a 30- to 60-min infusion every 4 weeks. After 4 episodes of anaphylaxis had occurred among the first 14 patients, the schedule was changed to a 24-h infusion, and an additional 16 patients were treated on this schedule. Treatment was given every 3 weeks. A total of 30 patients were eligible and evaluable; there were 3 (10%; 90% confidence interval, 3%-23%) clinical responses lasting 3, 3+, and 12 months, respectively. The most serious toxicity encountered was anaphylaxis, which occurred in 5 patients, although with no serious sequelae. A premedication regimen with dexamethasone, diphenhydramine, and cimetidine and a change of the duration of the infusion to 24 h reduced the incidence of this complication. Grade 2-3 vomiting occurred among earlier patients treated; however, with the 24-h schedule this toxicity was substantially reduced. The sole important case of hematologic toxicity was a single patient with grade 3 thrombocytopenia. Echinomycin employed in this dose and schedule had modest activity against colorectal cancer, comparable with that observed with 5-fluorouracil. Further studies in patients with gastrointestinal malignancies using a 24-h infusion with a dexamethasone premedication regimen similar to that employed prior to administration of taxol may be warranted.

Adenocarcinoma

Treatment of carcinoma of the esophagus with 5-fluorouracil and recombinant alfa-2a-interferon.

BACKGROUND: Combinations of 5-fluorouracil (5FU) and recombinant alfa-2a-interferon (IFN) are synergistic in vitro and have demonstrated activity in colorectal carcinoma, renal cell carcinoma, and urothelial tumors. METHODS: A Phase II trial of the combination of 5FU, 750 mg/m2 daily x 5 followed by weekly bolus therapy, and IFN, 9 MU subcutaneously three times per week, was initiated in patients with esophageal carcinomas. Patients were required to have biopsy-proven squamous cell or adenocarcinoma of the esophagus, locally advanced or metastatic disease beyond the scope of surgical resection, and adequate performance status, renal, hepatic, and bone marrow function. RESULTS: Twenty-one patients were enrolled; one patient was inevaluable for response because he had received prior chemotherapy, but was evaluated for toxicity. Eleven patients had metastatic disease, and 10 had locally advanced disease. Thirteen patients had squamous cell carcinoma and 8 adenocarcinoma. Toxicities were acceptable with no serious diarrhea and only two cases of serious stomatitis, although a greater than expected incidence of neurologic toxicity was observed. There were five responders (25%) including two patients with advanced or locally advanced disease rendered pathologically free of disease. One patient, initially considered surgically unresectable, was able to undergo a total thoracic esophagectomy after responding to treatment with 5FU/IFN, at which time only a single microscopic focus of carcinoma in situ was found. She remains alive and free of disease at 18+ months. A second patient who presented with metastatic disease and nearly complete obstruction of the esophagus regained normal swallowing function after treatment with 5FU/IFN; rebiopsy of all lesions revealed the patient to be pathologically free of disease. He survived over 2 years. CONCLUSIONS: This regimen employing a single cytotoxic agent has activity in esophageal carcinoma. Strategies employing biochemical modulation deserve additional investigation in the treatment of esophageal carcinoma.

Adenocarcinoma

Pilot trial of cisplatin, radiation, and WR2721 in carcinoma of the uterine cervix: a New York Gynecologic Oncology Group study.

PURPOSE: A phase I trial of WR2721 was initiated to determine the maximal safe dose for incorporation into a consecutive 5-day schedule of cisplatin administered concurrently with radiation therapy in patients with cervical cancer. PATIENTS AND METHODS: WR2721 was administered at 340 to 910 mg/m2/d immediately before cisplatin. Cisplatin was administered at 20 mg/m2/d for 5 days every 3 weeks in combination with external-beam radiation therapy and at 100 mg/m2 after each brachytherapy treatment. Pelvic radiation consisted of external-beam therapy to a dose of 39.6 Gy, followed by brachytherapy with cesium 137 tandem and ovoid insertions to deliver 80 Gy to point A and 55 Gy to point B. RESULTS: Twenty patients were enrolled; 19 were assessable. The dose-limiting toxicity of WR2721 was hypotension. No patients developed serious sequelae, but hypotension required a reduction in the dose of WR2721 at the highest dose level tested. The major grade 3 or 4 toxicities included transient azotemia (five of 19), leukopenia (nine of 19), vomiting (four of 19), and neurotoxicity (two of 19). One patient experienced an anaphylactic reaction to cisplatin. CONCLUSION: The recommended dose of WR2721 administered in conjunction with cisplatin on a daily x 5 schedule plus radiation therapy is 825 mg/m2/d for 5 days.

Adenocarcinoma