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Biomedical subjects

J M Klausner

Publications and source records attributed to J M Klausner.

At least 37 records · Page 2Linked to original sources

Neurotoxicity of isolated limb perfusion with tumor necrosis factor.

Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor alpha (TNFalpha) is effective for advanced melanoma and sarcoma of the limbs. Ten patients undergoing HILP with TNFalpha were evaluated by neurological examinations, nerve conduction studies (NCS), sympathetic skin responses (SSR) and conventional and quantitative electromyography (EMG), performed before, 7 days and 6 weeks following HILP. Seven patients showed minimal clinical signs of peripheral nerve damage following HILP; in two the injury was evident electrophysiologically: 7 days following HILP five patients had paresthesias and/or hypoesthesia, one had a mild foot drop and one had autonomic disturbances in the affected limb. SSR was low in two patients in the affected limb, sensory nerve action potentials were not elicited in one, with normal motor NCS and EMG. At 6 weeks, four patients continued to have mild paresthesias and one had dysautonomia of the perfused limb. Sensory responses and SSR did not change, motor abnormalities were not found. These findings show that HILP with TNFalpha induces a mild, mainly sensory neuropathy in perfused limbs, not disturbing functionality and improving over time.

Adult↗

Optimizing laparoscopic splenectomy. Technical details and experience in 59 patients.

BACKGROUND: Laparoscopic splenectomy (LS), like other advanced laparoscopic procedures, is still an evolving procedure. The indications for surgery, criteria for patient selection, and operative technique are not yet well defined. We have therefore modified the standard technique for performing LS in an attempt to optimize the procedure. METHODS: Over the past 2 years, we have performed LS in 59 patients. The last 43 patients were operated using a standardized technique that we believe to be optimal. It includes the routine use of the right lateral position, operating through three trocars, the mass transection of the splenic vasculature with a vascular endoscopic stapler, and the use of a self-retaining retrieval bag. RESULTS: The average operating time was 79 min. Average blood loss was 95 cc, and average postoperative hospitalization was 2.3 days. There was one intraoperative complication and one postoperative complication. These results are superior to those we achieved earlier in our own experience, as well as to similar series that have been published recently. CONCLUSIONS: In our experience, the use of this new technique resulted in relatively short procedures with low morbidity. We believe that these results justify the use of LS as the procedure of choice for elective splenectomy in patients with normal or moderately enlarged spleens.

Disease-Free Survival↗

High dose tumor necrosis factor-alpha and melphalan administered via isolated limb perfusion for advanced limb soft tissue sarcoma results in a >90% response rate and limb preservation.

BACKGROUND: Recombinant tumor necrosis factor-alpha (rTNF-alpha) is a highly potential antineoplastic agent. However, its systemic administration in humans has resulted in a life-threatening septic shock-like syndrome, and its use has been abandoned. The administration of high dose rTNF-alpha and melphalan via isolated limb perfusion (ILP) eliminated the systemic side effects and was shown to be very effective for metastatic melanoma confined to the limb. The purpose of the current study was to assess the role of rTNF-alpha and melphalan administered via ILP in patients with soft tissue sarcoma. Amputation is unavoidable in 10% of these patients despite aggressive conventional therapy. Limb preservation was the objective in this select group of candidates for amputation or mutilating surgery. METHODS: During a 36-month period, 35 patients with high grade soft tissue sarcoma underwent 41 ILPs with high dose rTNF-alpha (3-4 mg) and melphalan (1-1.5 mg/kg). There were 21 males and 14 females. The mean age was 48 years (range, 14-80 years). Histologic subtypes included malignant fibrous histiocytoma, synovial, liposarcoma, malignant schwannoma, desmoid, clear cell, epithelioid, rhabdomyosarcoma, leiomyosarcoma, and unclassifiable. Twenty-one patients presented with recurrent and 14 with very extensive primary tumors. The tumors were located in the upper extremity in 8 patients and in the lower extremity in 27 patients. Twenty-five patients were candidates for amputation and 10 for extensive mutilating surgery. ILP was performed via the corresponding vessels proximal to the tumor. Six patients with partial response (PR) insufficient to render them resectable underwent a second ILP. With the exception of 4 of 9 patients with multifocal lesions and 1 who refused surgery, resection of the residual tumor or tumor bed or limb was performed 6-8 weeks after ILP. RESULTS: Marked tumor softening occurred within 48 hours, and in tumors protruding through the skin hemorrhagic necrosis was evident within 24 hours. The overall response rate was 91%. Thirteen patients (37%) had a complete response and 19 (54%) had a PR; in 5 of these patients > 90% necrosis of the tumor occurred. In 3 patients (8.5%), only minimal regression was observed (stabilization of disease). The rate of limb sparing was 85% (29 of 34 patients). CONCLUSIONS: The combination of high dose rTNF-alpha and melphalan given via ILP appears to be effective in patients with advanced soft tissue sarcoma confined to the limb, achieving a high response rate and limb preservation.

Adolescent↗

Surgery in Israel.

The evolution and development of surgery in Israel reflects the influence of its dramatic historical events. The immigration of surgeons, particularly since the fourth decade of the 20th century, highly contributed to the framework of modern surgery. Medical education occurs at 4 medical schools, in Jerusalem, Tel Aviv, Haifa, and Beer Sheva, and postgraduate surgical training takes place in all public hospitals, most of which are university hospitals or have university-affiliated departments, and is controlled by the Scientific Council of the Israel Medical Association (Tel Aviv). Health care is provided by 4 health insurance funds and has been recently influenced by the National Health Insurance Bill and the Bill of Patient's Rights. Surgical standards are high and similar to the very best of Western countries. The geographical location of Israel in the Middle East, surrounded by hostile Arab countries, has dramatically influenced the development of Israeli surgery. The practice of surgery ranges from full-time service in state and insurance-funded mostly academic hospitals, to private part-time clinics for wealthy and insured patients. Surgical training occurs only in departments accredited by the Scientific Council, which are mostly affiliated with the 4 medical schools. A surgical residency in Israel usually requires 6 years, and its guidelines and regulations are elaborated and recommended by the Israel Surgical Society and controlled by the Scientific Council. Most Israeli surgeons were trained in Israeli hospitals, but a substantial number of surgeons immigrated to the country, especially from eastern Europe.

Curriculum↗

Isolation limb perfusion with tumor necrosis factor alpha and chemotherapy for advanced extremity soft tissue sarcomas.

The unique property of high dose recombinant tumor necrosis factor alpha (rTNF alpha) is to activate and selectively destroy the tumor-associated microvasculature. For the systemic application of rTNF alpha it has been shown that the maximum tolerated dose (MTD) is 10 times less than the effective dose in animals. The main toxicity corresponds to systemic inflammatory response syndrome with a decrease in vascular resistance and hypotension. We found that it is possible to administer rTNF alpha at 10 times the MTD in an isolated limb perfusion (ILP) system with heart-lung machine, for locally advanced extremity soft tissue sarcomas. One hundred forty patients received an ILP with high-dose TNF alpha. In 55 patients treated with the combination of high-dose rTNF alpha + interferon-gamma + melphalan an overall objective response rate of 87% with 36% complete responses was observed; it was 81% and 28%, respectively, in a group treated with TNF alpha and melphalan (n = 85). Angiographic and immunohistological studies showed the selective and early damage of the sarcoma-associated microvasculature preceded by the upregulation of adhesion molecules and intratumoral leak of von Willebrand factor. Tumor invasion by platelets and, in some cases, by polymorphonuclear cells, appeared within hours after the application of rTNFa long before the lysis of the tumor. Thus, ILP with high-dose TNF alpha and chemotherapy seems to act through a dual targeting: TNF hits the tumor associated vasculature, and chemotherapy attacks the tumor cells. Therefore, ILP with TNF is a new option in the management of locally advanced soft tissue sarcoma of the extremities.

Adolescent↗

Synergism of tumor necrosis factor-alpha and melphalan in systemic and regional administration: animal study.

Tumor necrosis factor (TNF) is a highly cytotoxic cytokine. However, due to its severe side effects, the only clinical situation allowing its administration in humans is isolated limb perfusion (ILP). Early studies have shown that TNF alone is of limited efficacy even at high doses via ILP, and that a chemotherapeutic agent needs to be added. The most commonly used drug in this setting is melphalan which is considered to be synergistic with TNF. However, since melphalan has not been commonly used in sarcoma, we believed that confirmation of its synergistic effect with TNF in an experimental sarcoma model could prove valuable for future drug choice. B16F10 melanoma and CT26 colon carcinoma cells were injected subcutaneously (s.c.) into mice, while GF fibrosarcoma cells were injected s.c. into the hindleg of Wistar rats. The animals were then divided into four treatment groups: TNF alone, melphalan alone, TNF and melphalan, and 0.9% NaCl controls. Mice were treated with intraperitoneal injections and rats by ILP. TNF dosage was 20 microgram for mice and 200 microgram for rats. Melphalan was given at 5-10 mg/kg for both mice and rats. Results showed synergism of TNF and melphalan in both modes of therapy. In the systemic administration groups (mice carrying B16F10 and CT26 tumors), tumors increased in size in all but the combined TNF-melphalan group. In the regional delivery groups (rats carrying GF sarcoma cells treated via ILP), there was a 16% decrease in tumor volume in rats treated with TNF alone, a 29% decrease in rats treated with melphalan, and a 75% decrease in the combined TNF-melphalan group. In conclusion, TNF and melphalan proved to be highly synergistic in both systemic and regional delivery. This fact makes melphalan an adequate choice for TNF perfusion in advanced limb malignancies.

Animals↗

Regional perfusion with hemofiltration (chemofiltration) for the treatment of patients with regionally advanced cancer.

BACKGROUND: Regionally advanced cancer is a common, often unresolved problem. Effective local control with chemotherapy is limited by the toxicity following systemic administration. Chemofiltration (CF) is a form of regional perfusion that enables the administration of cytotoxic drugs into one body area while limiting systemic toxicity. The drug is infused into the artery supplying the involved area. The venous effluent of the same organ is pumped out into a hemofiltration unit at a high flow rate. The drug is then filtered away and the blood returned to systemic circulation. METHODS: Forty-one patients underwent 45 CF. Twenty-four patients had CF of the pelvis for advanced rectal carcinoma (10), malignant melanoma (6), and cancers of the uterine cervix (3), ovary (2), vulva (1), endometrium (1), and anus (1). Seventeen patients underwent CF of the liver for metastatic colon (10), breast (4), pancreas (1), ovary (1), and unknown primary (1) cancer. 5-fluorouracil (1 g/m2) and mitomycin-C (30 mg/m2); cisplatinum (200 mg/m2) alone or combined with bleomycin (50 mg/m2) and mitomycin-C (20 mg/m2); or melphalan (1 mg/kg) were the combinations used. RESULTS: Generally the procedure was well tolerated. Complications included transient leukopenia (18), paralytic ileus (2), hair loss (2), renal failure (1). Two patients died within 40 days following CF. Of 36 evaluable patients, 16 (44%) had partial response, 14 (38%) had stable disease, and 6 (18%) had disease progression. A decrease of at least 30% in carcinoembryonic antigen levels occurred in 12 of 24 patients (50%). Median time to progression was 7 months. Ten of 13 patients (77%) achieved good symptomatic palliation. CONCLUSIONS: The results of CF in our study are not superior to alternative methods of drug delivery to the liver and pelvis. However, considering that previous systemic chemotherapy had failed two-thirds of the patients, some benefit may be attributed to this regional delivery modality. Furthermore, pelvic CF afforded very significant symptomatic relief which was definitely superior to other methods.

Adult↗

[Packing and abbreviated laparotomy in the injured--a life-saving procedure].

Packing of abdominal viscera and abbreviated laparotomy are gaining favor among surgeons for cases with multiple injuries. During a 2-year period, 10 patients required abbreviated exploratory laparotomy for abdominal trauma. The 6 records which were complete form the basis of this study. 3 patients were hypotensive at the scene of injury and in the emergency department. Major vascular injury was encountered in 4. The only procedures attempted at the initial operation were packing bleeding solid viscera and controlling bleeding and fecal spillage. Hypothermia, acidosis and need for massive blood transfusion were indications for terminating exploration without attempting definitive surgery.

Abdominal Injuries↗

Increased microvascular permeability induced by prolonged interleukin-2 administration is attenuated by the oxygen-free-radical scavenger dimethylthiourea.

Effective use of interleukin (IL)-2 as an antineoplastic agent may be hindered by severe side-effects, in particular vascular leak syndrome, which leads to generalized, especially pulmonary, edema. The oxygen-free-radical scavenger dimethylthiourea (DMTU) was shown to attenuate IL-2-induced vascular leak syndrome in sheep receiving a single IL-2 injection. However, in the clinical setting multiple injections are necessary to gain a therapeutic effect. The present study tests whether DMTU attenuates IL-2-induced vascular leak syndrome following multiple IL-2 injections without affecting IL-2-induced cytotoxicity in peritoneal mononuclear cells. Mice were treated intraperitoneally with 1 x 10(5) units IL-2 three times daily for four consecutive days. DMTU (10 mg/0.5 ml) was administered to the study group once daily, prior to the first IL-2 injection. Comparing the wet/dry weight ratio of lungs, liver, and spleen showed that IL-2 caused a significant (P < 0.05) wet/dry increase in all three organs. DMTU attenuated the wet/dry increase in the lungs (P < 0.05), in the spleen (P < 0.05), and not at all in the liver. IL-2 induced a marked increase in peritoneal mononuclear cell counts, which was not attenuated by DMTU. The cytotoxic effect of IL-2-activated peritoneal mononuclear cells on target B16 cells was also unchanged in animals pretreated with DMTU. In conclusion, we have shown that DMTU ameliorates pulmonary permeability and vascular leak syndrome associated with multiple-dose IL-2 therapy, without eliciting an inhibitory effect on IL-2 induced-cytotoxicity.

Animals↗

Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experience.

OBJECTIVE: The objective of the study was to achieve limb salvage in patients with locally advanced soft tissue sarcomas that can only be treated by amputation or functionally mutilating surgery by performing an isolated limb perfusion (ILP) with tumor necrosis factor (TNF) + melphalan (M) as induction biochemotherapy to obtain local control and make limb-sparing surgery possible. SUMMARY BACKGROUND DATA: To increase the number of limb-sparing resections in the treatment of locally advanced extremity soft tissue sarcoma, preoperative radiation therapy or chemotherapy or a combination of the two often are applied. The ILP with cytostatic agents alone is another option but rarely is used because of rather poor results. The efficacy of the application of TNF in ILP markedly has changed this situation. METHODS: In 8 cancer centers, 186 patients were treated over a period of almost 4.5 years. There were 107 (57%) primary and 79 (43%) recurrent sarcomas, mostly high grade (110 grade III; 51 grade II; and 25 very large, recurrent, or multiple grade I sarcomas). The composition of this series of patients is unusual: 42 patients (23%) had multifocal primary or multiple recurrent tumors; median tumor size was very large (16 cm); 25 patients (13%) had known systemic metastases at the time of the ILP. Patients underwent a 90-minute ILP at 39 to 40 C with TNF + melphalan. The first 55 patients also received interferon-tau. A delayed marginal resection of the tumor remnant was done 2 to 4 months after ILP. RESULTS: A major tumor response was seen in 82% of the patients rendering these large sarcomas resectable in most cases. Clinical response rates were: 33 complete response (CR) (18%), 106 partial response (PR) (57%), 42 no change (NC) (22%), and 5 progressive disease (PD) (3%). Final outcome was defined by clinical and pathologic response: 54 CR (29%), 99 PR (53%), 29 NC (16%), and 4 PD (2%). At a median follow-up of almost 2 years (22 months; range, 6-58 months), limb salvage was achieved in 82%. Regional toxicity was limited and systemic toxicity minimal to moderate, easily managed, with no toxic deaths. CONCLUSIONS: In the setting of isolated limb perfusion, TNF is an active anticancer drug in patients. The ILP with TNF + melphalan can be performed safely in many centers and is an effective induction treatment with a high response rate that can achieve limb salvage in patients with locally advanced extremity soft tissue sarcoma.

Adolescent↗

Intra-arterial chemotherapy with concomitant hemofiltration (chemofiltration) for treatment of loco-regional or pelvic metastases from malignant melanoma.

Loco-regional or pelvic metastases from malignant melanoma (MM) of the lower limbs or pelvis are usually refractory to systemic chemotherapy, the limiting factor being systemic toxicity. An attempt to improve this low response rate using a novel loco-regional approach involving intra-arterial high dose chemotherapy with concomitant hemofiltration of the venous effluent of the pelvis, hence chemofiltration, was studied. Chemofiltration was performed in seven MM patients. The arterial catheter and the venous cannula were placed in the aorta and the inferior vena cava just distal to the renal vessels. High-dose melphalan (1 mg/kg) or cis-platinum (200 mg/m2) was injected into the arterial catheter. Blood was pumped out into the hemofiltration unit at a rate of 500-700 ml/min. The filtered blood was returned via a catheter placed in the superior vena cava. Despite the extensive fluid exchange (9,700-15,000 ml), the procedure was well tolerated. Out of six patients who remained with measurable disease, three had a partial response lasting 5-12 months, two had stabilization of their disease for 3 months, and one developed a rapid progression. Chemofiltration is feasible in MM patients and is a viable option in locally advanced or metastatic malignant melanoma confined to the limb or pelvis.

Aged↗

[Isolated limb perfusion with tumor necrosis factor for malignancies of the limbs].

Tumor necrosis factor (TNF) induces rapid necrosis in a variety of experimental neoplasms. However, its clinical application is limited by life-threatening systemic toxicity. Isolated limb perfusion (ILP) enables administration of large doses of TNF and cytotoxic drugs directly to the affected limb, avoiding systemic toxicity. We describe our experience in 20 consecutive patients (10 with melanoma and 10 with soft tissue sarcoma) treated with high-dose TNF and melphalan via ILP. ILP was performed via the external iliac (10 cases), femoral (2), popliteal (5) or brachial (3) vessels. Patients received 3-4 mg TNF to an upper, and 1-1.5 mg/kg to a lower extremity. Isolation efficiency was determined by injection of radiolabelled albumin. The procedure was successful in all 20 patients. Local complications included wound infection in 6 cases and hematoma in 2. 1 patient developed sepsis secondary to extensive necrosis of a large, secondarily infected tumor. The first 6 patients who underwent high-flow perfusion experienced systemic side-effects, mainly hypotension. These side-effects were eliminated when low-flow perfusion was introduced. The response rate was 100%. In the sarcoma group, 5/10 had complete response, and 5 partial response. Amputation or mutilating surgery was avoided in 9/10. Of the 10 with melanoma, 7 had complete, and 3 partial response. We conclude that administration of TNF via ILP is a safe and effective modality for treating advanced neoplasms of the limbs.

Adolescent↗

Heparin-induced thrombocytopenia and fatal thrombosis in a patient with activated protein C resistance.

We report a 20-year-old woman who developed heparin-induced thrombocytopenia (HIT) associated with devastating and fatal multiorgan thrombosis. The patient, her mother, and her brother were found to have resistance to activated protein C (APC), and the congenital thrombophilia in this family was verified by the finding of the Arg506 Gln mutation in factor V. This is the first case of HIT and APC resistance. The consequences of this association are discussed.

Adult↗

Soluble tumor necrosis factor receptors reduce bowel ischemia-induced lung permeability and neutrophil sequestration.

OBJECTIVES: To evaluate the possible role of tumor necrosis factor (TNF) in the development of lung injury after bowel ischemia, and the ability of TNF-soluble receptors to negate TNF toxicity, using a rat small bowel ischemia and reperfusion model. DESIGN: Prospective, randomized, controlled laboratory study. SETTING: Research laboratory. SUBJECTS: Forty adult male Sprague-Dawley rats weighing approximately 300 g. INTERVENTIONS: The rats were divided equally into four groups: a) ischemia and reperfusion alone; b) those animals receiving TNF antibodies (1 mL) before reperfusion; and c) those animals receiving 200 micrograms of human recombinant TNF soluble receptors. These 30 anesthetized rats underwent 60 mins of superior mesenteric artery occlusion per 4 hrs of reperfusion. The remaining ten animals were sham operated (laparotomy), serving as controls. Lung permeability was measured using bovine serum albumin labeled with 125I, and organ injury was assessed histologically. MEASUREMENTS AND MAIN RESULTS: Thirty and 60 mins after declamping and reperfusion, plasma TNF concentrations increased to 830 +/- 66 and 173 +/- 56 pg/mL, respectively, compared with 10 pg/mL before ischemia (p < .001). In sham-operated control rats, TNF concentrations did not increase from baseline concentrations. Four hours after reperfusion, sequestration of neutrophils in the pulmonary microcirculation was noted (319 +/- 60 vs. 84 +/- 13 neutrophils/10 high-power fields in sham-operated rats [p < .04]). Pulmonary microvascular leak also occurred, as measured by translocation of radiolabeled albumin into the bronchoalveolar space and expressed as the ratio of bronchoalveolar lavage to blood concentrations. This ratio was 5.3 +/- 0.8 in ischemic control animals compared with 1.1 +/- 0.3 in sham animals (p < .03). Treatment with antibodies to TNF before reperfusion attenuated the pulmonary injury (75 +/- 6 neutrophils/10 high-power fields, permeability index 1.6 +/- 0.1) less than in ischemic controls (p < .005). A similar protection was achieved with soluble TNF receptors, which prevented bowel ischemia-induced lung neutrophil sequestration (117 +/- 35 neutrophils/10 high-power fields, pulmonary vascular leak ratio of 2.3 +/- 0.1, p < .05). CONCLUSIONS: The results of this study show that ischemia and subsequent reperfusion of the intestine in rats produce lung injury. This injury is mediated, at least in part, by TNF. Soluble TNF receptors are an effective tool in preventing lung TNF injury after intestinal ischemia.

Animals↗

Late abdominal complications in war wounded.

Complications possibly related to battle injuries are not necessarily discovered immediately postwounding, but may surface many months or years later. Sometimes, the relationship is evident, but often it is difficult to prove the connection. Between 1975 to 1989, we treated 260 veteran wounded from Israel's wars (1948 to 1982). Of these, 122 patients suffered from abdominal complaints, and this study relates only to this group. Eighty percent of them had undergone surgery caused by abdominal trauma at the time of the original injury, and the remaining 20% were injured in areas other than the abdomen. Their complaints manifested several weeks to 35 years postinjury. Diagnosis was delayed for 1 to 8 years in 70% of the patients. Acute or chronic pain, dyspepsia, intolerance to certain foods, early satiety, nausea, vomiting, distension, disturbances in bowel movements, and discharge from unhealed wounds were the most frequently encountered complaints. After evaluation and diagnostic work-up, it was possible to establish diagnosis and afford appropriate treatment in 97 (77%) of the patients. Peptic ulcers were found in 31 patients; 10 required surgery for ulcer-related complications. Acute and repeated attacks of intestinal obstruction occurred in 19 patients; 14 required surgery. The cause of obstruction was adhesions in nine, and strictures, incarcerated hernias, and abscess formation in the rest. Ventral hernias at surgical, ostomy, and drain sites were found and repaired in 49 patients. Abdominal wall sinuses originating from foreign bodies or osteomyelitis were found in 13 patients, and low output enterocutaneous fistulas were found in three patients. Chronic abdominal abscesses were found in 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Pain↗

[Chemofiltration for locally advanced cancer].

In chemofiltration a large dose of a cytotoxic drug is infused into an artery supplying a cancerous area, thus limiting systemic toxicity. The venous return from the area is pumped into a chemofiltration unit at 750 ml/min and the drug is filtered out of the blood, which is then returned to the systemic circulation. Of 22 patients with locally advanced cancer, systemic chemotherapy had failed in 63%. 9 of them underwent chemofiltration of the liver for advanced metastatic cancer of the colon (4 cases), rectum (2), breast (2) and ovaries (1); and 13 underwent chemofiltration of the pelvis for advanced cancer of the rectum (5), malignant melanoma (5), ovaries (1), cervix uteri (1) and vulva (1). The following drugs were used: 5-FU (750 mg/m2/10 min) and mitomycin-C (30 mg/m2/10 min) for colorectal, ovarian and breast carcinomas; melphelan (1 mg/kg/20 min) or cisplatinum (200 mg/m2/30 min) for malignant melanoma or ovarian carcinoma; mitomycin-C or bleomycin (50 mg/m2/10 min) for carcinoma of the cervix or vulva. 1 patient with extensive liver metastases died of respiratory failure 28 days after the procedure. Surgically related complications occurred in 16% and included wound hematoma (2 cases), infection (1) and venous thrombosis (1). Drug-related complications occurred in 50%, and included transient leukopenia (9), mild renal failure (1), hair loss (2) and prolonged paralytic ileus (1). Partial remission was observed in 10/20 patients who had measurable disease. Time to progression was 5.4 months (range: 4 weeks to 20 months). Stabilization of disease occurred in 7/20 (35%), while in 3 the disease progressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗