Morning Report

1. Morning Report With Miller and Dr. Polite

2. MKSAP • Three years ago, a 67-year-old man underwent right hemicolectomy with adjuvant chemotherapy for stage III colon cancer. The patient has been followed with annual CT scans and measurement of serum carcinoembryonic antigen (CEA) levels. His most recent CEA level is 10.1 ng/mL (10.1 µg/L) (normal <2.0 ng/mL [2.0 µg/L]) compared with a value of 2.4 ng/mL (2.4 µg/L) 1 year ago. A restaging CT scan of the abdomen and pelvis shows a solitary lesion in the liver and is otherwise unremarkable.

3. Which of the following is the most appropriate initial treatment? • A. Chemoembolization • B. Chemotherapy • C. Ethanol ablation • D. Radiofrequency ablation • E. Surgical resection

4. The primary anatomic location of metastatic colon cancer is the liver. Between 20% and 30% of patients with metastatic disease following curative surgery will have isolated hepatic metastases. • In these patients, regional treatment of hepatic metastases may be an alternative to systemic chemotherapy and result in better survival. • This patient with previous colon cancer has a solitary site of recurrent disease after a 3-year disease-free period. Surgical resection is potentially curative in approximately 25% of patients with these findings. • Contraindications to resection include tumors that are too large, unfavorable anatomic location, multiple tumors, poor hepatic function, and poor performance status. Chemotherapy may convert previously inoperable lesions into lesions amenable to surgical intervention. • Other local ablative techniques include cryosurgery, chemoembolization, ethanol ablation, and radiofrequency ablation. These options may be considered for local control in a patient who is not a surgical candidate. Although these techniques are unlikely to be curative, they may prolong progression-free survival.

5. The Case… • 46 yo lady with ho metastatic breast CA, was outside at a BBQ in August, feeling well. She began having word finding difficulty followed by RUE contraction. She fell down and began foaming at the mouth.

6. HPI • Patient with aphasia, then tonic-clonic activity for ~1min, then there was a post-ictal period. Patient was without memory of event. No tongue biting, bowel or bladder dysfunction. • No prior fevers, chills, night sweats, nausea, vomiting, or wt loss. • No HA, photophobia, meningismus • No Chest pain, SOB, light headedness, or palpitations • Patient transferred from an outside hospital after intubation for repeat clonic-tonic episode and airway protection… records have not yet arrived.

7. Medications Zometa Pericolace Tylenol 650 Morphine SR 15mg BID Allergies Aranesp causes flushing Social Hx PhD candidate of philosophy, married with three children. No TOB, EtOH, or Illicits Family Hx First cousin and two second cousins died of breast ca < 40 yo. PMHx Metastatic Breast Ca -T2N2Mx ER/PR +, HER-2 – 2000 dx’d with infiltrating ductal carcinoma 11/2000 modified radical mastectomy with adjuvant chemo-XRT. 2003-2009 she had recurrence to disease involving bilateral ribs, thoracic spine, lumbar spine, marrow involvement, liver, and lung. She received multiple chemo regimens at an OSH during this time. Her last chemo regimens included bevacizumab and abraxane, followed by Doxorubicin 3 weeks prior to admission. H/o neutropenia in 1/08

8. Differential

9. Seizure Differential/Etiologies R/O mimmickers of Sz, most commonly Syncope, Pseudoseizure, alcoholic blackouts, hypoglycemia, migraines, TIA’s narcolepsiy. Trauma or intracranial abnormality Tumor or Metastasis with or without bleed. Getting bonked in the head Vascular Stroke (hemorrhagic, large size, or cortical involvement) Intracerebral hemorrhage, subarachnoid hemorrhage, subdural hematoma, hypertensive encephalopathy, global hypoxic damage, cerebral vascular dz Hemangioma, auto-immune Metabolic encephalopathy hypoglc, nonketotic hyperglc, hypoNa, hypoCa, Uremia, hepatic encephalopathy, thyroid dysregulation Dementia Intracranial infection Meningitis, encephalitis, abscess Rx/intoxication Etoh withdrawal, illicit drug use (local anesthetics, meperidine, tramadol [Ultram]) Antibiotics (e.g., beta-lactam antibiotics, isoniazid [INH; Nydrazid], quinolones, some HAART meds) Immunomodulators (e.g., cyclosporine, interferons, tacrolimus,) Psychotropics (e.g., antidepressants, lithium, stimulants) Theophylline

10. Physical Exam Respiratory Vented, moving air well throughout Gastrointestinal S/NT/ND/BS+/No masses No rebound or gaurding Muskuloskeletal Grossly normal upper and lower extremity strength Neuro + gag, PERRLA No passive neck stiffness. Upper and Lower extremities with 2+ reflexes, Bilaterally downward babinsky. Nl Rectal tone. VitalsT 36.9, BP 101/40, HR 80, RR12, O2 satting 98% on AC GEN Intubated and unresponsive HEENT Optic disc sharp bilaterally, PERRL, no nystagmus or preferential gaze. LAD No cervical, supraclavicular, axillary, or cervical LAD CV RRR, without murmurs, rubs, nl S1 S2, warm and well perfused with no JVD, no LE edema

11. Labs?

12. Labs 7.8 139 105 25 4.2 22 0.9 6.7 4.0 0.8 78 66 145 2.0 4.6 GFR 67 60 15.4 1.2 8.9 MCV 108 4.2 70 N 86 L6 M8 + Left Shift 29 Lactate 1.9 CK – 198 MB- 1.8 RI 0.9 Trop 0.0 UA- WNL

13. Head CT • EPIC

14. CT read 3cm mass in the left frontotemporal junction, 5 x 2.3 cm mass in the posterior lateral left frontal parietal junction, multiple 1-2 cm lesions in the frontal lobes, diffuse edema in the Left temporal lobe, mild edema in the right temporal lobe, posterior left frontal lobe. No midline shift or herniation. Mild para-nasal sinus disease. MRI suggested

15. MRI The cortical sucli ventricles cisterns are prominent for patients stated age, and c/w cerebral and cerebellar atrophy. Edema in left temporal lone and R parietal lobe, most c/w metastases. Dural metastases along the left temporal bone w surrounding edema and multiple lesions in the inner left frontal bone with hyperdensity c/w hemorrhage vs calcification. No midline shift or herniation. Spinal portion: Diffuse bony metastatic disease involving the entire spine vertebral columns, sacral ala, and iliac wings. There is no evidence of intra-spinal metastasis.

16. Next Step?

17. CT before LP when… Age >60 Immunocompromised New onset seizure or seizure within past week Altered mental status Focal neuro findings h/o CNS dz Finding of elevated ICP (papilledema)

18. LP Opening pressure was not performed CSF clear • Glc 101 • Prot 35 • RBC 894 • WBC 31 • N65 L6 M 29 • Bacterial Cx’s neg

19. CSF Interpretation

20. Aseptic Meningitis

21. Clinical Course Decadron, and Dilantin had been initiated by the OSH. Treatment for bacterial meningitis with Vanc, high dose Ceftriaxone (2g) is initiated based on CSF pleocytosis.

22. Hospital course • Patient was awoken, passed SBT, and was extubated on hospitalization Day 2. Neuro was consulted and she exhibited no signs or symptoms of neurologic deficits. • CSF pleocytosis attributed to seizure. Antibiotics were discontinued.

23. Our Patients Cytology • Adenocarcinoma c/w breast in origin. Diff Quik Stained x 1, Cytospin Slide - Papanicolaou Stained x 1 Representative slide

24. Carcinomatous Meningitis • A type of Neoplastic Meningitis Meningitis 2/2 malignant infiltration from SOLID TUMOR progression (as apposed to leukemic or lymphomatous meningitis) Origin: 1) Hematogenous spread via arachnoid vessels 2) Metastasis to the choroid plexus and from there into the CSF 3) Direct extension from brain parenchyma, or from vertebral, subdural, epidural metastases 4) Retrograde neural invasion (peripheral or cranial nerves) 5) rarely, tumors arise within meninges 6) Post-surgical resection of a brain tumor

25. Carcinomatous Meningitis • Estimated ~5% incidence in Breast CA, ? growing % in the setting of taxanes (poor CSF penetration) and patients living longer with disease. • Prognosis: Poor. Median survival is 2-6 months • Cases are best managed with supportive and/or palliative therapy as guided by patients clinical status, cancer type, co-morbidities, access to resources.

26. Clinical Findings

27. Diagnosis • Definitive test is LP for Cytology (highly specific but sensitivity is 40% with 1st LP, 80% with 2nd) • Supporting evidence LP findings (opening pressure >20cmH2O), Leukocytes>4/mm3, elevated protein >50mg/dl, glc <60 mg/dl, tumor antigens MRI with gadolinium is preferred to look for enhancement/any meningeal irritation and characterize CNS lesions. (cranial and spinal) • OTHER Radionuclide studies to evaluate CSF flow

28. Treatment • Limited by lack of standarized therapy as most studies are small nonrandomized and retrospective, the diagnostics provide suboptimal sensitivity, and patients typically die of systemic disease. • However, treatment can provide clear palliative benefit, and in some cases prolong survival • Weapons: Radiation, chemo, and surgery (vps or ommaya placement)

29. Evaluation

30. XRT indications 1)Decrease bulky disease (intra-CNS chemo only penetrates 2-3mm into tumors) 2)Correct CSF flow abnormalities (shown to improve patient outcome) 3)Palliation of symptoms (i.e. cauda equina syndrome, Cranial neuropathies)

31. Cinical Course • Patient discharged within 3 days. Given concern of bulky tumors and for ? decreased CSF flow, she received whole brain XRT. • A follow up MRI demonstrated good generalized response. • Radionucleotide Ventriculography was obtained to evaluate CSF flow.

32. Radionucleotide Ventriculography 24 hrs post indium-111 administration, good flow was seen throughout the ventricles

33. Intra-thecal Chemotherapy • Mainstay of therapy for Carcinomatous Meningitis, though there is mounting evidence for systemic therapy in certain conditions. • Three most common agents are MTX, cytarabine, lipasomal cytarabine, and thiotepa • Delivered through a ventricular catheter with a SQ reservoir or through LP

34. Ommaya • Bleeding and infection risk • Avoid burdensome LP’s • 10 times improved drug delivery (LP does not guarantee drug delivery)

35. Further clinical Course • Patient was initiated on intrathecal liposomal cytarabine, but low level cytology remained positive via serial LP. She similarly failed thiotepa and topotecan. • During the next ~9mo’s she continued to work diligently on her dissertation for her PhD in philosophy. She helped her daughter select a college. • She lived for 10 months past her 1st seizure, eventually succumbing to complications of marrow suppression, and hemorrhage.

36. Take home Know indications for imaging prior to tap Know how to diagnose Carcinomatous meningitis and when to suspect it Know importance of diagnosis of carcinomatous meningitis Indications for XRT in the setting of carcinomatous meningitiss Be familiar with Ommaya delivery system

37. References • Chamberalain. Marc, Neoplastic Meningitis, The Oncologist 2008;13:967-977 • Chowdhary. S, Leptomeningeal Metastases: Current Concepts and Management Guidelines, JNCCN Sept. 2005;3;5;693-702 • Adams. S, Evaluation of first seizure. AAFP 2009;75;9;May 1 • Epic • www.uptodate.com