Chemosaturatie. Ingrid Veldema

Transcription

1 Chemosaturatie Ingrid Veldema

2 procedure

3 ChemoSat Chemofiltration Circuit Assembly and Operation

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5 Male or female patient > 18 years of age with a life expectancy of at least 3 months Weight > 35kg Surgically unresectable primary or metastatic cancer of the liver. No chemotherapy, radiotherapy, or biologic therapy for 1 month prior to treatment Must have recovered from all side effects of therapeutic and diagnostic interventions 5

6 ECOG performance status of 0 to 1 at screening and on the day prior to each treatment Adequate hepatic function Total serum bilirubin < 3.0 mg/dl PT within 2 seconds of upper normal limit AST/ALT must be < 10 times upper limit of normal Adequate hematologic and renal function Platelet count > 75,000/dL, Hgb > 9 gm/dl (correctable with transfusion), WBC ANC > 1.3 k/pl Serum creatinine < 1.5 mg/dl (unless measured creatinine clearance is > 60mL/min/1.73m) 6

7 History of hypersensitivity to heparin or presence of a heparin induced thrombocytopenia (HIT) antibodies History of bleeding disorders or evidence of intracranial abnormalities that would put patient at risk for bleeding with anticoagulation Patients with a history of gastrinoma or who have undergone a Whipple procedure Patients with any previous surgery that may have altered the vascular or biliary anatomy of the liver 7

8 Patients with infections Severe allergic reactions to iodinated contrast, which cannot be controlled by premedication with antihistamines and steroids Known prior hypersensitivity reaction to Melphalan Documented latex allergy 8

9 Childs B or C cirrhosis or evidence of portal hypertension by history, endoscopy, or radiologic studieshistory of congestive heart failure, with an LVEF < 40%Significant COPD or other chronic pulmonary restrictive disease with PFT s indicating an FEV1 less than 30% or a DLCO less than 40% predicted for age Pregnant patient or nursing mother Patient taking immunosuppressive drugs or requiring ongoing chronic anticoagulation 9

10 Patient preparation Prior to the CHEMOSAT procedure, there are several laboratory assessments, imaging tests and treatments that are necessary to evaluate patients The following slides break down patient preparation by length of time prior to scheduled procedure: 4 weeks prior At least 1 week prior 10

11 Concomitant Disease Assessment Patients with known cardiac disease (i.e., history of myocardial infarction, chest pain, cardiac arrhythmias or CHF) should undergo screening for occult ischemic coronary artery disease with an exercise induced or stress thallium scan Patients with pulmonary disease (i.e., obstructive or restrictive pulmonary disease) should undergo formal pulmonary function test (PFT) Technetium 99 radionucleotide bone scan when clinically indicated For patients with 50% or greater liver replacement by tumour on medical imaging, a biopsy of non-involved liver parenchyma must be performed to show that it is histologically normal Patients with prior history of peptic ulcer disease should undergo endoscopy to evaluate the risk for potential for GI toxicities. Consider Proton Pump Inhibitor (PPI) as needed. MRI of the brain 11

12 History & Physical Examination A thorough pertinent history and physical examination is mandatory Imaging Studies Baseline Computed Tomography or Magnetic Resonance Imaging of Chest/Abdomen/Pelvis to document extent of disease, including abdominal CTA or MRA Baseline MRI or CT of the brain to rule out intracranial abnormalities with propensity to bleed Consider baseline PET scans for follow-up of treatment effect Baseline Laboratory Work-up SMA-20, CBC, LFTS, PT/PTT 12

13 Pre-menopausal Women Women who are pre-menopausal (have had a period within the past 12 months) will receive appropriate hormonal suppression as prescribed by treating physician. This is a precautionary step that is taken to suppress menstruation in order to prevent excessive bleeding due to anticoagulation during menstruation. 13

14 Patients should undergo a repeat complete history and physical examination and laboratory evaluation Complete Blood Count (CBC) Prothrombin Time (PT) Partial Thromboplastin Time (PTT) International Normalized Ratio (INR) Serum Chemistry, electrolytes, renal function Liver Function Tests (LFT) 14

15 Baseline imaging studies CT or MRI (repeat only if indicated) Baseline imaging of abdomen (including CTA or MRA), chest and pelvis to document extent of disease and to follow progress with treatment Brain CT or MRI (repeat only if indicated) Rule out intracranial abnormalities with a propensity to bleed Angiogram (Conventional) The arterial supply to the liver must be completely examined, and its impact on chemotherapy infusion assessed and understood. Embolization of hepatic artery branches may be required. Ample time (~ one week to 10 days) should be allowed. This will allow for healing of the puncture site. Embolization on the day of the procedure is discouraged because subsequent heparinization may interfere with stable clot formation within the embolized vessel. 15

16 Chronic Use of Angiotensin-Converting Enzyme Inhibitors (ACEI), Angiotensin-Receptor or Ca ++ Chanel Blockers, or Amiodarone for treatment of hypertension* Inform Anesthesiologist Above hypertension therapy must be temporarily discontinued at least one day prior to the procedure, preferably earlier to resolve their effects Place on temporary replacement therapy during periprocedure period Restart chronic medication after PHP *Reference: Levin MA, Lin HM, Castillo JG, Adams DH, Reich DL, Fischer GW. Early On-Cardiopulmonary Bypass Hypotension and Other Factors Associated with Vasoplegic Syndrome. Circulation. 2009;120:

17 Blood Products (Type & Cross) Packed RBC, Fresh Frozen Plasma, Platelets, Cryoprecipitate Hydration Beginning night prior to procedure Antibiotics History of hepatobiliary surgery Allopurinol Prevent Tumor-lysis Syndrome (if Tumor Burden >25%) 2 3 days before and following perfusion Proton Pump Inhibitors (known or suspected Peptic Ulcer Disease) Gastritis prevention Calculate dose of melphalan and notify pharmacy of procedure timing proactively 17

18 The preoperative angiograms should include: Celiac and superior mesenteric artery injection Evaluation of portal venous supply, including splenic, superior mesenteric and portal veins to determine patency and direction of flow Assessment for variant hepatic arterial and aberrant gastrointestinal branches to prevent inadvertent infusion of GI or visceral branches Formulate strategy for catheter placement to ensure adequate drug infusion to the tumor If CTA not available, perform Inferior Vena Cava-gram Determination of optimal balloon spacing (50mm or 62mm) Embolization: to avoid reflux or infusion into GI or Visceral arteries Gastroduodenal artery (GDA) Left gastric artery (LGA), Right Gastric Artery (RGA) Hepatic variant anatomy (e.g., replaced hepatic artery) Aberrant or unusual anatomical variants 18

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21 ISOLATION Inflate and Wedge Cephalad Balloon of Isolation Aspiration Catheter at the junction of the Atrium and the Superior Vena Cava Inflate Caudal Balloon of Isolation Aspiration Catheter to complete Hepatic venous isolation Ref P-023-A

22 Specially designed isolation-aspiration catheter in IVC allows hepatic chemosaturation by effectively isolating the liver from the systemic venous circulation.

23 CHEMOSAT Components

24 CHEMOSATURATION PROCEDURE

25 Ultra-high doses of a chemotherapy agent are then introduced intra-arterially into the isolated liver, saturating the entire organ.

26 Chemofiltration Circuit SYSTEM OVERVIEW Infuuszak met Melphalan Ontluchter en spike verbinding

27 Chemofiltration Circuit SYSTEM OVERVIEW Large bore 3- weg kraan onderdeel van het systeem Tip van de spuit van de injector.

28 Chemofiltration Circuit SYSTEM OVERVIEW Naar injector Microcatheter met ook een 3-weg kraantje

29 A. Hepatic venous blood is captured by the isolation-aspiration catheter and directed outside the body to proprietary filters. B. Filters reduce the concentration of chemotherapeutic agent of this blood before it is returned to the body.

30 Chemofiltration Circuit SYSTEM OVERVIEW Chemofiltration Begins Chemosaturation Begins

31 Chemofiltration Circuit SYSTEM OVERVIEW

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33 Perfusion Flow ml/min 30 min perfusion Melphalon HCI 30 min wash out System Pressure guide -p = <30mmHg Pre Pump -p = >120mmHg Post Pump End of perfusion: 1000ml Ringer to deprime tubings (blood back to patient)

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35 35 Tumorblush

36 Middle Left Right 36 Gastroduodenalis

37 37 Coiling Gastroduodenalis

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45 Since march 2013 Referral by Multi Disciplinary Meetings 7 patients/12 procedures: 3 ocular melanoma 2 NET 1 melanoma 1 bileduct carcinoma No PHP related SAE s Partial response in all cases

46 Pat Gende r Ag e Primary I C U Hospit al stay respons e PH P Status after first PHP 1 F 60 Bileduct 1 5 PR 1 Died 7 mo PD 5 mo 2 F 66 Ocular 1 3,3,3 PR 3 Alive 2 years PD 20 mo 3 M 58 NET 1 4 PR 1 Died 15 months PD 6 mo 4 F 53 Ocular 1 2,3 PR 2 Died 8 mo PD 6 mo 5 M 37 Ocular 1 3,3,3 PR 3 Died 1 year PD 8 mo 6 M 57 NET 1 3 PR 1 Alive 18 months PD 7 F 40 Melanom a 1 3 unknow n 1 Alive 1 month

47 Chemosaturation is a promising treatment option in selected cases primary and secondary liver cancer Feasable, short hospital stay, easy to repeat New generation filters leads to low incidence bone marrow depression Registry, protocols and new studies are needed Reimbursement

48 Trial together with Leiden university for colorectal livermetastasis. Treatment for Livermetastasis oculair melanoma

49 Met dank aan: