Effectiveness of Nifurtimox in the Treatment of Chagas Disease: a Long-Term Retrospective Cohort Study in Children and Adults.

Chagas disease (ChD), caused by Trypanosoma cruzi, has a global prevalence due to patient migration. However, despite its worldwide distribution, long-term follow-up efficacy studies with nifurtimox (NF) are scarce and have been conducted with only small numbers of patients. A retrospective study of a large cohort of ChD treated children and adults with NF. Treatment response was evaluated by clinical, parasitological, and serological after-treatment evaluation. A total of 289 patients were enrolled, of which 199 were children and 90 adults. At diagnosis, 89.6% of patients were asymptomatic. Overall, all symptomatic patients showed clinical improvement. At baseline, parasitemia was positive in 130 of 260 (50%) patients. All but one adult patient had cleared their parasitemia by the end of treatment. That patient was considered a treatment failure. Median follow-up time for children was 37.7 months, with an interquartile range of (IQR25-75 12.2 to 85.3), and for adults was 14.2 months (IQR25-75, 1.9 to 33.8). After treatment, a decrease of T. cruzi antibodies and seroconversion were observed in 34.6% of patients. The seroconversion profile showed that, the younger the patient, the higher the rate of seroconversion (log rank test; P value, <0.01). At least 20% seroreduction at 1 year follow-up was observed in 33.2% of patients. Nifurtimox was highly effective for ChD treatment. Patients had excellent treatment responses with fully resolved symptoms related to acute T. cruzi infection. Clearance of parasitemia and a decrease in T. cruzi antibodies were observed as markers of treatment response. This study reinforces the importance of treating patients during childhood since the treatment response was more marked in younger subjects. (This protocol was registered at ClinicalTrials.gov under registration number NCT04274101).

Adverse Events Associated with Nifurtimox Treatment for Chagas Disease in Children and Adults.

Nifurtimox (NF) is one of the only two drugs currently available for Chagas disease (ChD) treatment. However, data on NF safety are scarce, and many physicians defer or refuse NF treatment because of concerns about drug tolerance. In a retrospective study of adverse drug reactions (ADRs) associated with NF treatment of ChD, children received NF doses of 10 to 15 mg/kg/day for 60 to 90 days, and adults received 8 to 10 mg/kg/day for 30 days. A total of 215 children (median age, 2.6 years; range, 0 to 17 years) and 105 adults (median age, 34 years; range, 18 to 57 years) were enrolled. Overall, 127/320 (39.7%) patients developed ADRs, with an incidence of 64/105 adults and 63/215 children (odds ratio [OR] = 3.7; 95% confidence interval [CI], 2.2 to 6.3). We observed 215 ADRs, 131 in adults (median, 2 events/patient; interquartile range for the 25th to 75th percentiles [IQR25-75], 1 to 3) and 84 in children (median, 1 event/patient; IQR25-75 = 1 to 1.5) (Padjusted < 0.001). ADRs were mainly mild and moderate. Severe ADRs were infrequent (1.2% in children and 0.9% in adults). Nutritional, central nervous, and digestive systems were the most frequently affected, without differences between groups. Treatment was discontinued in 31/320 (9.7%) patients without differences between groups. However, ADR-related discontinuations occurred more frequently in adults than in children (OR = 5.5, 95% CI = 1.5 to 24). Our study supports the safety of NF for ChD treatment. Delaying NF treatment due to safety concerns does not seem to be supported by the evidence. (This study has been registered in ClinicalTrials.gov under identifier NCT04274101.).

Fine, Vascular Network Formation in Patients with Vein of Galen Aneurysmal Malformation.

BACKGROUND AND PURPOSE: A vein of Galen aneurysmal malformation is known to present with recruitment of dural feeders and, in our cohort, a fine, vascular network formation. The vessels we have observed differ from dural vascular recruitment in that they produce a hairlike, collateral network of vessels. We reviewed treatment courses of vein of Galen aneurysmal malformation treatments in a series of 36 cases that displayed a fine, vascular network formation. MATERIALS AND METHODS: We retrospectively analyzed 36 cases of vein of Galen aneurysmal malformation, including tectal/thalamic AVMs, treated at our center from January 2004 to September 2021, and reviewed fine, vascular network formations in the subarachnoid space and subependymal zone alongside the vein of Galen aneurysmal malformation. RESULTS: Patients at first endovascular treatment ranged from neonates to 157 months (median age, 4.3 months). Patients with preinterventional fine, vascular network formations were significantly older at the initial angiogram than patients with postinterventional fine, vascular network formations (P < .05). On average, for 20 control choroidal/mural vein of Galen aneurysmal malformations whose treatment course had been completed and in which no plexiform network was visualized, a mean of 2.63 (SD, 1.64) treatments were required to achieve a radiographic cure. For the 36 choroidal/mural vein of Galen aneurysmal malformations whose treatment course had been completed and in which a fine, vascular network formation was visualized, a mean of 5.94 (SD, 2.73) treatments were required to achieve a radiographic cure (P < .01). CONCLUSIONS: Development of a fine, vascular network formation is an acquired and reversible phenomenon that differs from typical dural vessel recruitment, given the hairlike nature of the network and its rapid onset postinterventionally. It typically resolves after completion of treatment, and this resolution correlates with closure of the vein. We recommend that neurointerventionalists avoid delays in treatment wherever possible to reduce the likelihood of a fine, vascular network formation.

A Radiologic Grading System for Assessing the Radiographic Outcome of Treatment in Lymphatic and Lymphatic-Venous Malformations of the Head and Neck.

BACKGROUND AND PURPOSE: Two-thirds of lymphatic malformations in children are found in the head and neck. Although conventionally managed through surgical resection, percutaneous sclerotherapy has gained popularity. No reproducible grading system has been designed to compare sclerotherapy outcomes on the basis of radiologic findings. We propose an MR imaging-based grading scale to assess the response to sclerotherapy and present an evaluation of its interrater reliability. MATERIALS AND METHODS: A grading system was developed to stratify treatment outcomes on the basis of interval changes observed on MR imaging. By means of this system, 56 consecutive cases from our institution with formally diagnosed head and neck lymphatic malformations treated by sclerotherapy were retrospectively graded. Each patient underwent pre- and posttreatment MR imaging. Each study was evaluated by 3 experienced neuroradiologists. Interrater reliability was assessed using the Krippendorff α statistic, intraclass coefficient, and 2-way Spearman ρ correlation. RESULTS: The overall Krippendorff α statistic was 0.93 (95% CI, 0.89-0.95), denoting excellent agreement among raters. Intraclass coefficients with respect to consistency and absolute agreements were both 0.97 (95% CI, 0.96-0.98), illustrating low variability. Every combination of individual rater pairs demonstrated statistically significant (P < .01) linear Spearman ρ correlations, with values ranging from 0.90 to 0.95. CONCLUSIONS: The proposed radiographic grading scale demonstrates excellent interrater reliability. Adoption of this new scale can standardize reported outcomes following sclerotherapy for head and neck lymphatic malformation and may aid in the investigation of future questions regarding optimal management of these lesions.

Angiographic and Clinical Features of Noninvoluting Congenital Hemangiomas.

While infantile hemangiomas are very common, congenital hemangiomas are rare and less understood. Congenital hemangiomas are present at birth. They fall into 2 major categories: rapidly involuting congenital hemangioma and noninvoluting congenital hemangioma. Noninvoluting congenital hemangioma is the rarer of the 2 entities. If not recognized and treated appropriately, noninvoluting congenital hemangioma can lead to considerable morbidity. There is a paucity of literature regarding noninvoluting congenital hemangiomas. In this article, we will outline our experience with this condition, focusing on clinical and angiographic features. There is a distinct angiographic appearance of noninvoluting congenital hemangiomas involving an arterial-capillary web, a dense tumor blush with identifiable feeding arteries, no arteriovenous shunting, and variably present draining veins. Our experience with endovascular embolization and direct percutaneous treatment is the largest for this entity to date. Endovascular embolization and/or direct percutaneous sclerotherapy of this lesion may obviate subsequent surgical resection.

The utility of DynaCT in neuroendovascular procedures.

The authors present 3 patients who underwent neuroendovascular procedures in which DynaCT produced by a flat-panel detector facilitated management of complications. As part of a combined CT/angiography suite, DynaCT offered the major advantage of immediate detection or exclusion of intracranial complication without patient transfer. The quality of cone-volume CT-generated images produced by DynaCT was sufficient to make a diagnosis.

Treatment of cerebral aneurysms with hydrogel-coated platinum coils (HydroCoil): early single-center experience.

PURPOSE: The authors report their experience using HydroCoils in the treatment of cerebral aneurysms. METHODS: We performed a retrospective review of the first 100 nonrandomized patients (104 coiled saccular cerebral aneurysms) treated with HydroCoils during a 27-month period. RESULTS: The average percentage of HydroCoil by length detached in treated aneurysms was 45.5% (range, 9.9-100%). Immediate postprocedure angiography demonstrated complete aneurysm occlusion in 34%, neck remnant in 35%, and incomplete occlusion in 32%. Immediate procedure-related morbidity and mortality rates were 5.8% and 0%, respectively. Angiographic follow-up was obtained in 51% (51/100 patients; 53/104 aneurysms; average, 10.3 months; range, 0-31 months). In these 53 angiographically followed aneurysms, the overall recanalization rate was 21%: no recanalization occurred in 23 aneurysms with small size (<10 mm)/small neck (<4 mm) (S/S); 4 recanalizations occurred in 7 aneurysms with small size/wide neck (>4 mm) (S/W); 6 recanalizations (27%) occurred in 22 large (L) aneurysms (>10-25 mm, 70% angiographic follow-up); and 1 giant (G) (>25 mm) aneurysm recanalized. A large proportion of aneurysms that were not initially completely occluded were completely occluded on follow-up (15/43 [35%]). Clinical follow-up was obtained in 73 patients (73%; average, 5.3 months; range, 0-24 months): 93% of these patients were neurologically improved or unchanged. Three patients rehemorrhaged and 3 patients with unruptured aneurysms developed delayed hydrocephalus. CONCLUSIONS: The overall safety profile of HydroCoils appears acceptable. Preliminary midterm observations suggest less coil compaction/aneurysm recanalization in large aneurysms. However, HydroCoil-related delayed hydrocephalus is a concern.

Occlusion of Posterior Fossa Dural Sinuses in Vein of Galen Malformation.

BACKGROUND AND PURPOSE: Spontaneous or progressive occlusion of the posterior fossa dural sinuses is often observed in patients with vein of Galen malformation, which can affect the clinical course. The aim of this study was to examine the patency of the posterior fossa dural sinuses in patients with vein of Galen malformation and to analyze the clinical and angiographic course of this condition. MATERIALS AND METHODS: We retrospectively reviewed 61 consecutive children with vein of Galen malformations. Clinical presentation, management, outcome, and angiographic change were analyzed for the patients with attention paid to all dural sinus occlusions. RESULTS: Twenty patients (32.8%) demonstrated spontaneous sinus occlusion, mostly in the sigmoid sinus. This condition was not observed in neonates and was first discovered during infancy or childhood. Progression of sinus occlusion was seen in 10 patients, and the conditions of 6 of them deteriorated in accordance with the progression of sinus occlusion. After total or subtotal obliteration of the malformation by transarterial glue embolization, 13 patients recovered to healthy, 3 patients had only mild developmental delay, and 4 patients remained neurologically disabled. CONCLUSIONS: Spontaneous sinus occlusion is not a rare condition and can result in neurologic deterioration in the natural history of untreated vein of Galen malformation. If signs of progressive sinus occlusion are noticed, early arteriovenous shunt reduction or elimination by transarterial glue embolization is expected to prevent permanent brain damage.

The Preventive Effect of Endovascular Treatment for Recurrent Hemorrhage in Patients with Spinal Cord Arteriovenous Malformations.

BACKGROUND AND PURPOSE: Spinal cord AVMs represent rare and insufficiently studied pathologic entities. Embolization is thought to play an important role in the management of spinal cord AVMs. Factors for recurrent hemorrhage and the impact of endovascular treatment on prevention of recurrent hemorrhage remain to be confirmed. We aimed to assess recurrent hemorrhagic incidence of spinal cord AVMs and its prevention by endovascular treatment. MATERIALS AND METHODS: We reviewed 80 patients with spinal cord AVMs by spinal cord angiography who had hemorrhage before the first endovascular treatment at New York University Medical Center, Beth Israel Medical Center, or Roosevelt Hospital in New York. We compared the baseline and radiologic characteristics of patients with and without recurrent hemorrhage by the log-rank test and the Cox proportional hazards model. RESULTS: We observed recurrent hemorrhage in 35 (44%) patients (1/41 patients with endovascular treatment and 34/39 patients without endovascular treatment). The median length of total follow-up was 659 days (interquartile range, 129-2640 days), and the median length from first-to-recurrent hemorrhage was 369 days (interquartile range, 30-1596 days). The log-rank test revealed that endovascular treatment and venous thrombosis reduced recurrent hemorrhage, and associated aneurysm was related to recurrent hemorrhage. Even in multivariate analysis, the endovascular treatment reduced (hazard ratio, 0.027; P < .0001) and associated aneurysm increased (hazard ratio, 3.4; P = .044) the risk of recurrent hemorrhage. CONCLUSIONS: Endovascular embolization is the first choice of treatment for spinal cord AVMs and is effective in preventing recurrent hemorrhage.

The New York Islands AVM Study: design, study progress, and initial results.

BACKGROUND AND PURPOSE: Prospective population-based data on the incidence of brain arteriovenous malformation (AVM) hemorrhage are scarce. We studied lifetime detection rates of brain AVM and incident AVM hemorrhage in a defined population. METHODS: The New York islands (ie, Manhattan Island, Staten Island, and Long Island) comprise a 9,429,541 population according to the 2000 census. Since March 15, 2000, all major New York islands hospitals have prospectively reported data on consecutive patients living in the study area with a diagnosis of brain AVM and whether the patient had suffered AVM hemorrhage. Patients living outside the ZIP code-defined study area were excluded from the study population. RESULTS: As of June 14, 2002, 284 prospective AVM patients (mean+/-SD age, 35+/-18 years; 49% women) were encountered during 21,216,467 person-years of observation, leading to an average annual AVM detection rate of 1.34 per 100,000 person-years (95% CI, 1.18 to 1.49). The incidence of first-ever AVM hemorrhage (n=108; mean age, 31+/-19 years; 45% women) was 0.51 per 100,000 person-years (95% CI, 0.41 to 0.61). The estimated prevalence of AVM hemorrhage among detected cases (n=144; mean age, 33+/-19 years; 50% women) was 0.68 per 100,000 (95% CI, 0.57 to 0.79). CONCLUSIONS: Our prospective data, spanning 27 months, suggest stable rates for AVM detection and incident AVM hemorrhage. Approximately half of AVM patients may suffer intracranial hemorrhage.

Optic tract atrophy with cerebral arteriovenous malformations: direct and transsynaptic degeneration.

Three patients with postgeniculate cerebral arteriovenous malformations (AVM) had band atrophy of the contralateral optic nerve. One patient had homonymous hemioptic hypoplasia. These cases might have been construed as demonstrating transsynaptic degeneration across the lateral geniculate nucleus to the anterior visual pathway. However, neuroimaging studies revealed abnormal deep venous drainage remote from the AVM nidus that directly involved the lateral geniculate nucleus and posterior optic tract.

Bilateral orbital signs predict cortical venous drainage in cavernous sinus dural AVMs.

BACKGROUND: Most cavernous sinus dural arteriovenous malformations (CSdAVM) have a benign clinical course. Those CSdAVM that drain into cortical veins have an increased risk for neurologic complications. OBJECTIVE: To find whether a specific clinical sign predicts cortical venous drainage (CVD) in CSdAVM. METHODS: The records of 118 patients with CSdAVM were evaluated for the clinical features of the disorder and tested for predictive value of CVD demonstrated angiographically or suggested by MRI using logistic regression and odds ratio (OR) analysis. RESULTS: Clinical signs that predicted the presence of CVD included bilateral orbital signs (p = 0.004, OR = 23.84) and presence of a postauricular bruit (p = 0.035, OR = 23.8). No other clinical sign predicted the presence of CVD, including extraocular muscle dysfunction, abducens or oculomotor dysfunction, increased intraocular pressure, venous stasis retinopathy, choroidal effusion, optic neuropathy, subjective bruit, and objective orbital bruit. CONCLUSION: Patients who present with or develop bilateral orbital congestion should be recognized as being at increased risk for CVD.

Occipital arteriovenous malformations: visual disturbances and presentation.

BACKGROUND: Occipital arteriovenous malformations (AVMs) cause a variety of visual disturbances and headaches. Early diagnosis may lead to treatment that reduces the risk of hemorrhages, visual field loss and other neurologic deficits, and death. METHODS: We reviewed the records of the 70 patients with occipital AVMs referred to New York University Medical Center to investigate the mode of presentation and the outcome of treatment. RESULTS: Sixty-eight patients presented with one or more symptoms, including homonymous visual disturbances in 39, headache in 39, seizures in 20, and hemorrhage in twenty-six. Visual field loss was more common (p = 0.0007) and more severe (p = 0.0002) in patients who bled than in those with unruptured AVMs (16/44). The frequency of visual field loss was not associated with calcarine artery supply to the AVM. Prior to treatment, the fields improved in five patients with visual loss associated with a hemorrhage. Forty-six patients were treated with embolization, surgery, radiosurgery, or a combination of therapies. The AVM was eliminated in 19 of 20 patients (nine with preoperative partial embolization) treated with surgery versus in 4 of 27 patients treated only with embolization. There were two AVM-associated deaths, two subarachnoid hemorrhages, and four new neurologic deficits after treatment. Visual fields were worse in 15 patients, unchanged in 22, and improved in eight. CONCLUSIONS: Whereas some features of headache and visual symptoms are similar for occipital AVMs and migraine, the two disorders are usually distinguishable. Visual field improvement can spontaneously occur in patients who have had loss secondary to an intracerebral bleed. Treatment with embolization or surgery, particularly with surgical excision of the AVM, can result in new or worse visual field loss.

Percutaneous transvascular treatment of giant carotid aneurysms: neuro-ophthalmologic findings.

Twelve of 17 patients with cavernous carotid aneurysms had balloon embolization directed through a percutaneous double lumen catheter for progressive pain, ophthalmoplegia, or visual loss. Functional angiography was carried out with systemic heparinization and double-lumen balloon catheters to test tolerance to carotid occlusion. Eleven were successfully treated, though two patients with initial preservation of the ipsilateral carotid artery had unplanned deflation of the balloon, necessitating re-embolization. No serious permanent neurologic complications occurred. All patients had complete resolution of pain, and nine had improvement in the extraocular eye muscle and lid function. Balloon trapping of the cavernous carotid artery, rather than placing the balloon directly into the aneurysm, resulted in involution of the aneurysm and decompression of the involved cranial nerves.

Visual symptoms with dural arteriovenous malformations draining into occipital veins.

OBJECTIVE: To determine the cause of the visual dysfunction and effect of treatment on dural arteriovenous malformations (DAVMs) that secondarily involve the occipital lobe. BACKGROUND: DAVMs are an infrequent cause of visual dysfunction that should be amenable to treatment if diagnosed before permanent visual field loss. METHODS: The records of seven patients with cerebral visual disturbances associated with DAVMs were analyzed with attention to visual symptoms, visual field testing, and vascular anatomy. RESULTS: Sudden visual loss occurred in five patients, two with a hemorrhage and one with a venous infarct in the occipital lobe. Fortification images occurred in three patients, two of whom had palinopsia (one with de novo formed visual hallucinations). Homonymous quadrantic or hemianoptic field defects, some fluctuating, were found in six patients. Angiography revealed each DAVM was supplied solely by dural arteries and drained into occipital pial veins due to retrograde blood flow through the sites near or in the wall or lumen of the dural venous channels that normally drain the occipital lobe. Unlike DAVMs in other locations, only two patients had occlusion of an adjacent venous sinus. These patients, particularly the two with posterior fossa DAVMs remote to the occipital lobe, clearly demonstrate the visual and neurologic dysfunction resulting from venous hypertension. In six patients, intra-arterial embolization of the arterial feeders and nidus (one patient required additional surgery) resulted in resumption of normal occipital venous emptying. No further visual episodes occurred in five of these six patients. The visual fields normalized in three patients and improved in one with venous infarct but were unchanged in both patients with a hemorrhage. CONCLUSIONS: DAVMs that drain into occipital veins cause field loss and other visual disturbances because of venous hypertension in the occipital lobe, which can be reversed by occluding the DAVM nidus. If a venous infarct or hemorrhage has not caused irreversible damage, visual recovery should be complete.

Visual system toxicity following intra-arterial chemotherapy.

We studied the effects of intra-arterial chemotherapy on the visual system of 29 consecutive patients with gliomas. As expected, infra-ophthalmic carotid infusion of cisplatin or carmustine (BCNU) was associated with clinically apparent anterior visual pathway lesions. Electroretinography revealed retinal dysfunction in patients without clinical abnormalities. Supra-ophthalmic carotid infusion of cisplatin or BCNU caused no retinal or optic nerve lesions. Electroretinography was abnormal in only one of these patients. Our results indicated that BCNU and cisplatin cause ischemic damage and are toxic to both retinal and neural tissue in patients with gliomas.

Supraophthalmic intracarotid infusion of BCNU for malignant glioma.

We treated five patients with 11 supraophthalmic infusions of BCNU at 200 mg/m2 every 2 months. All three patients with residual tumors showed marked CT response after one infusion. Two patients with bilateral tumors had no response on the contralateral side. All four evaluable cases showed evidence of BCNU neurotoxicity. CT findings superficially resembled tumor recurrence, but white matter changes, nonspecific gyral enhancement, and delayed calcification were more indicative of neurotoxicity. There were no procedure-related complications. One autopsy suggested that direct parenchymal damage might be responsible for delayed neurotoxicity. Supraophthalmic BCNU infusion, at this dosage, is too toxic for cerebral tissue.

Recent improvement in outcome using transcatheter embolization techniques for neonatal aneurysmal malformations of the vein of Galen.

Vein of Galen malformations may present as congestive heart failure in the neonate and are usually fatal if untreated. Early studies using transcatheter embolization techniques, in a series of 22 patients, had a 50% mortality rate and a 37% incidence of severe mental retardation in survivors. Modifications of embolization techniques and neonatal care have improved the outlook in a more recent series of 11 patients. The diagnosis was established within 3 days of life in 91% of the cases. No mortality occurred, and 6 of the patients were functionally normal at up to 30 months' follow-up. Although two patients had severe neurologic deficits and/or a seizure disorder, only one case was possibly temporally associated with the embolization procedure. Some developmental delay was noted in one other patient. These improvements result, in part, from modifications of the treatment protocol, including earlier diagnosis, avoidance of digoxin, improvement in the application of newer microcatheters and acrylic polymers (n-butylcyanoacrylate), avoidance of overly aggressive neurosurgical procedures, and the use of stable central vascular access for total parenteral nutrition accompanying other general improvements in neonatal care.

Neuroprotective role of neurophysiological monitoring during endovascular procedures in the spinal cord.

The endovascular treatment of spinal vascular malformations places the spinal cord at risk for ischemia. When these procedures are performed using general anesthesia, the neurophysiological monitoring methods currently available provide the only means by which to assess the functional integrity of sensory and motor pathways. Neurophysiological monitoring allows a warning for the neuroradiologist of impending irreversible neurological damage so that action may be taken for the prompt restoration of adequate spinal cord perfusion. Muscle motor evoked potentials (mMEPs) better reflect spinal cord perfusion in the anterior spinal artery territory than do somatosensory evoked potentials (SEPs), although their use during spinal endovascular procedures remains anecdotal in the literature. In the study reported here we assessed: (1) the feasibility of intraoperative neurophysiological monitoring, (2) the role of provocative tests with Amytal and Xylocaine, and (3) the specific but complementary role played by SEPs and mMEPs, during endovascular embolization of spinal vascular malformations and tumors. The results suggest that: (1) neurophysiological monitoring is feasible during most endovascular procedures in the spine and spinal cord under general anesthesia, (2) provocative tests enhance the safety of the procedure, (3) mMEPs are more feasible than SEPs and more sensitive than SEPs to provocative tests. We strongly suggest the use of multimodal neurophysiological monitoring and provocative tests during the endovascular treatment of spinal and spinal cord vascular lesions.

Microembolization techniques of vascular occlusion: radiologic, pathologic, and clinical correlation.

Vascular occlusion is described using microemboli of a predetermined size for the treatment of neoplastic conditions with a "capillary barrier." Particulated microemboli of either 40--60 micron Gelfoam powder or 200--1,000 micron polyvinyl alcohol foam (PVA) are best. Fluid embolic agents such as silicone fluid are used in lesions without a capillary barrier. The radiographic, pathologic, and clinical results in three patients are described in detail. Microembolization is useful in the treatment of neoplastic conditions for it produces tumor necrosis in addition to hemostasis.