melphalan and Ischemia

To identify risk factors for acute choroidal ischemia (ACI) after intra-arterial chemotherapy (IAC) for retinoblastoma.. Retrospective cohort study.. Two hundred twenty patients (248 eyes) treated with IAC in Lausanne between November 2008 and September 2019 (665 procedures). All patients were evaluated on a monthly basis with fundus photography and fluorescein angiography before and after each IAC injection.. Acute choroidal ischemia, defined as any new choroidal ischemia clinically diagnosed within 35 days after an IAC injection, were noted. Eyes with choroidal complications diagnosed later than 35 days after the last IAC injection (n = 7) or those for which the status of the choroid was not assessable (n = 35) were excluded. Specific procedure parameters and treatment regimens were compared between the group of eyes with and without ACI.. Procedure-related risk factors for ACI after IAC injection and visual acuity assessment in the group of eyes with ACI.. Acute choroidal ischemia developed in 35 of 206 included eyes after a mean of 2 injections. No differences were found between the two study groups regarding age at first IAC injection, disease grouping at diagnosis, previously administered treatments, number of IAC injections, drug dose, mean injection time, injection method (pulsatile vs. continuous), or concomitant intravitreal melphalan use. Treatment regimen (melphalan vs. combined melphalan plus topotecan; P < 0.05), catheterization route (internal carotid artery vs. external carotid or posterior communicating artery; P < 0.001), and catheterization type (occlusive into the ophthalmic artery [OA] vs. nonocclusive; P < 0.001) were included in multivariate analysis, and occlusive catheterization was identified as an independent risk factor for ACI (P < 0.001). In the subgroup undergoing an occlusive procedure, placement of the catheter tip into the OA distal third versus medial and proximal thirds (P = 0.04) and a mean catheter diameter-to-OA lumen ratio of 0.6 or more (P < 0.001) were correlated significantly with ACI. Complete vision loss was noted in 27% of the eyes with ACI that were old enough for visual assessment (n = 9/33), whereas 33% maintained a useful vision ranging between 0.1 and 0.8 (n = 11/33).. Catheterization of the OA should be attempted from an ostial position or an external carotid approach to minimize the risk of potentially vision-threatening choroidal complications.

Topics: Acute Disease; Adolescent; Adult; Antineoplastic Agents, Alkylating; Catheterization; Child; Choroid; Female; Fluorescein Angiography; Humans; Incidence; Infusions, Intra-Arterial; Ischemia; Male; Melphalan; Middle Aged; Ophthalmic Artery; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Risk Factors; Visual Acuity

Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to treat melanoma in-transit metastases confined to a limb. The aim of this international multi-centre study was to identify predictive factors for toxicity and response.. Data of 687 patients who underwent a first ILI for melanoma in-transit metastases confined to the limb between 1992 and 2018 were collected at five Australian and four US tertiary referral centres.. After ILI, predictive factors for increased limb toxicity (Wieberdink grade III/IV limb toxicity, n = 192, 27.9%) were: female gender, younger age, procedures performed before 2005, lower limb procedures, higher melphalan dose, longer drug circulation and ischemia times, and increased tissue hypoxia. No patient experienced grade V toxicity (necessitating amputation). A complete response (n = 199, 28.9%) was associated with a lower stage of disease, lower burden of disease (BOD) and thinner Breslow thickness of the primary melanoma. Additionally, an overall response (combined complete and partial response, n = 441, 64.1%) was associated with female gender, Australian centres, procedures performed before 2005, lower limb procedures and lower actinomycin-D doses. On multivariate analysis, higher melphalan dose remained a predictive factor for toxicity, while lower stage of disease and lower BOD remained predictive factors for overall response.. ILI is safe and effective to treat melanoma in-transit metastases. Predictive factors for toxicity and response identified in this study will allow improved patient selection and optimization of intra-operative parameters to increase response rates, while keeping toxicity low.

Topics: Age Factors; Aged; Aged, 80 and over; Amputation, Surgical; Antineoplastic Combined Chemotherapy Protocols; Australia; Chemotherapy, Cancer, Regional Perfusion; Creatine Kinase; Dactinomycin; Dose-Response Relationship, Drug; Female; Humans; Ischemia; Lower Extremity; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Metastasis; Sex Factors; Skin Neoplasms; Time Factors; Tourniquets; United States; Upper Extremity

We report the case of a 15-month-old boy with retinoblastoma who developed exotropia secondary to a right medial rectus infarct after intra-arterial chemotherapy. He had unilateral sporadic group C tumor (International Classification of Retinoblastoma) and was treated with intra-arterial melphalan. One week after the first session of intra-ophthalmic arterial melphalan chemotherapy, he was noted to have orbital congestion, exotropia, and right adduction limitation. Magnetic resonance imaging was suggestive of a right medial rectus infarct. The tumor showed a good response to intra-arterial chemotherapy but the exotropia persisted.

Topics: Antineoplastic Agents, Alkylating; Edema; Exotropia; Fluorescein Angiography; Humans; Infant; Infarction; Infusions, Intra-Arterial; Ischemia; Magnetic Resonance Imaging; Male; Melphalan; Muscular Diseases; Oculomotor Muscles; Ophthalmic Artery; Papilledema; Radiography; Retinal Neoplasms; Retinoblastoma

Topics: Antineoplastic Agents, Alkylating; Electroretinography; Humans; Infant; Infusions, Intra-Arterial; Ischemia; Male; Melphalan; Ophthalmic Artery; Retina; Retinal Artery Occlusion; Retinal Neoplasms; Retinal Vein Occlusion; Retinoblastoma

Topics: Adult; Aged; Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Colonic Neoplasms; Female; Humans; Ischemia; Liver; Liver Neoplasms; Male; Melphalan; Middle Aged

Light-chain deposition disease (LCDD) is a multisystemic disorder associated with plasma cell dyscrasias and multiple myeloma. It is histologically characterized by the deposition of a homogeneous, in electron microscopy granular, slightly eosinophilic material showing positivity usually for kappa light chains. In contrast to AL-amyloidosis, the material is negative for Congo red. LCDD mainly involves the kidneys as the predominant organ manifestation resulting in a nephrotic syndrome. However, involvement of other tissues such as liver and heart have been described. Here we report a case of severe ischemic cholangitis in a patient with multiple myeloma receiving chemotherapy with melphalan, prednisone, and lenalidomide. Histopathological analysis revealed LCDD of the hepatic arteries as the underlying cause. This is to our knowledge the first case of LCDD of terminal liver arteries as a cause of intrahepatic ischemic cholangitis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cholangitis; Hepatic Artery; Humans; Immunoglobulin Light Chains; Ischemia; Lenalidomide; Male; Melphalan; Multiple Myeloma; Paraproteinemias; Prednisone; Thalidomide

Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-alpha) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated.. Thirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up.. Five patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17-159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50-1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91-1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1-23.9 vs. median, 7.35; range, 4.8-21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0-21.4 vs. median, 10.95; range, 8.0-32.6; P < .0005). In patients with follow-up of >5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011).. ILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amputation, Surgical; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Humans; Ischemia; Limb Salvage; Male; Melphalan; Middle Aged; Radiotherapy, Adjuvant; Sarcoma; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha; Vascular Diseases