Download File - Prepared Rescuer, LLC

GRAND ROUNDS ~
RESPIRATORY FAILURE SECONDARY TO COMPLICATIONS
FROM METASTATIC SYNOVIAL CELL SARCOMA
Moderator / ICU: Dr Jeremy Barnett MD
Pulmonary / ICU: Dr Anthony Guerrino MD
Pharmacology: Priti Shah RPh
ED: Dr Amy Gutman MD
OBJECTIVES
 Multidisciplinary review of a oncological process with an rare complication with
significant impacts on management of critically ill patients
 3rd in the Kingston Hospital Grand Round Series
 ACCME application for accreditation initiated so state-required CME can be completed without
leaving Kingston
CASE PRESENTATION ~ CC & HPI
 33 yo M with history of metastatic synovial sarcoma reports 24 hours history of
increasing dyspnea
 Denies cough, fever, calf swelling, tenderness or prior history of similar events
 States that he had chest pain overnight, but not upon presentation. Also denies
hemoptysis, recent URI, abdominal pain, N/V/D, melena, hematochezia, recent
travel, prolonged immobility
CASE PRESENTATION ~ PMH
 PMH:
 Metastatic synovial sarcoma
 FAMILY:
 (-) pertinent
 ALLERGIES:
 NKDA
 MEDICATIONS:
 Opdivo (nivolumab)
 SOCIAL:
 (+) former smoker (10 PYH)
 (+) occasional ETOH
CASE PRESENTATION ~ ROS
Limited initially due to respiratory distress; ROS more fully explored with family
 GENERAL: (-) prior fever
 GU:
 HEENT:
(-) congestion
 SKIN / MS: (+) chronic pain
 PULM:
(+) cough, (+) SOB / DOE
(+) wheezing
 ENDO:
(+) generalized weakness
 NEURO:
(-) localized weakness
 PSYCH:
(+) emotional stress
 CV:
 GI:
(+) CP last night
(-) abdominal pain
(+) loss of appetite
(+) weight loss
(-) urinary complaints
CASE PRESENTATION ~ EXAM
VITALS: T 97.6 (oral)
 GENERAL:
 HEENT:
 PULM:
 CV:
HR 105 / reg
RR 30 / labored
A&Ox3, moderate
respiratory distress
Membranes moist, airway
patent; (-) conjunctival pallor,
stridor, hoarseness, neck
stiffness, LAD, JVD
BS = BL; (+) rhonchi, (+) rales; (-)
wheezes
RRR (-) MRG, (+) tachycardic
BP: 107/66
Sat 75% ra
Wt 63.5 kg
 GI:
Soft, NT, ND, BSAQ, cachectic
 GU:
(-) LAD
 MUSC:
Warm, dry, (-) cyanosis; surgical
scars over R olecranon, (+) right
PICC site CDI; (-) deformity,
edema, calf tenderness
 NEURO:
A&Ox3, afocal otherwise
 PSYCH:
Anxious but appropriate
CASE PRESENTATION ~ EKG
Sinus tachycardia, rate of 120, short pr (110ms) with an incomplete right bundle branch block (QRS
duration 100ms) & diffuse ST/T-wave changes including T-wave inversions & ST-depression
CASE PRESENTATION ~ LABS
 UA:
(+) Ketones
 Troponin:
<0.010
129
85
13
 LFTs:
Alk Phos 376 / T Bili 1.3
AST / ALT 56 / 34
Albumin 3.8
3.8
26
0.78
 Coags:
PTT / Pt / INR 42 / 12 / 1
 Lactic Acid:
21
 ABG:
 7.32 / 44 / 64 / 26 / 91 (FiO2 100%)
 COHb 2.5
133
13
16
228
39
AG = Na - (Cl + HCO3)
AG = 129 – (85 + 26) = 18
Hypochloremic normal anion gap acidosis
CASE PRESENTATION ~ ED IMAGING
 Extensive bilateral infiltrates
 Left pulmonary masses
 Hilar & mediastinal adenopathy
 Pleural effusions
CASE PRESENTATION ~ ED IMAGING
 No pulmonary artery filling defects
 Pleural, pericardial & skeletal metastasis
 Left pleural effusions w/o pericardial effusion
 Mediastinal adenopathy with diffuse thickening of
distal esophageal wall
 Bibasilar ground-glass consolidations with air
bronchograms representing lymphagitic
carcinomatosis vs pneumonitis
CASE PRESENTATION ~INITIAL
MANAGEMENT
 IV, O2, Monitor
 PICC access for initiation of sepsis protocol (O2, antibiotics, fluid resuscitation)
 45 mins post-presentation, on-coming MD reviewed all diagnostics, re-examined
patient & called his hospital of choice to arrange transfer




Patient progressively worsening from the respiratory standpoint, increasingly anxious
Advanced from NC to NRB, then high-flow O2 which patient did not tolerate
BiPAP not attempted as patient did not tolerate high-flow O2
At this point, patient declining intubation, though wished to be “resuscitated”
CASE PRESENTATION ~ ICU
CONSULTATION
 Intensivist consulted to assist from pulmonary & CV standpoints
 Despite an initial acceptance at his hospital of choice, after 2 hours of promises of an
open bed, the transfer was “put on hold until a bed was available”
 Intensivist accepted patient to the ICU rather than wait in ED for potential transfer
 Presumptive diagnoses of respiratory distress secondary to pneumonia, influenza,
underlying metastatic process
CASE PRESENTATION ~ CRITICAL
CARE MANAGEMENT
 Patient increasingly anxious, with worsening
oxygenation
 Patient & family agreed to intubation
 Immediately post intubation, he became hemodynamically
unstable requiring norepinephrine & fluid resuscitation
 CT reviewed, demonstrating pneumothorax




Likely secondary to tumor / scarring rupturing a bleb
Chest tube high risk due to scarring / masses
Continued on 100% FIO2
Large needle taped to patient’s chest
INITIATING MECHANICAL
VENTILATION ~ RATIONALE
 Airway Protection
 NO gas exchange derangements
 CNS or mechanical loss of airway protection / patency
 Hypoxic Respiratory Failure
 pO2 < 50 on 100% NRB
 Decreased ambient FiO2, increased pCO2, diffusion
block, V/Q mismatch, right-left shunt
 Hypercarbic Respiratory Failure
 pH < 7.3, pCO2 > 50
 Acute vs chronic, “Won’t” vs “Can’t”, CNS vs Bellows
www.nursingconsult.com
INITIATING MECHANICAL
VENTILATION
 Thoughtful process
 Use numbers to guide you
 If you can’t fix the process with non-invasive measures, then commit to
prophylactic intubation rather than wait until patient in extremis
 Allows patient to rest while you gather data & figure out how to manage their
physiological process(es)
 Remember, sometimes it is easy but wrong TO intubate….sometimes it is
easy & wrong NOT to intubate
NITROGEN WASHOUT TEST
 Gauges functional residual capacity & airflow
 Evaluates for dead space without gas exchange
 Usually caused by non-functional alveolar capillaries not absorbing
O2 or expelling CO2
 Dead space decreases lung efficiency function
 To accurately measure effects a lung disease will have
on lung function the test evaluates for:





Volume: overall amount of air filling lungs
Capacity: actual amount of air used in regular breathing
Functional Residual Capacity: amount of unused air in lungs
Diffusing Capacity: ability of alveoli to absorb O2 into bloodstream
Airflow: physical ability to pull in & expel air
ICU COURSE
 100% FiO2 / low PEEP x until PTX resolved
 Pan-cultured while initiated / continued on:
 Antibiotics: Piperacillin-tazobactam, Vancomycin,
Meropenem
 Antiviral: Oseltamivir
 Antifungal: Micafungin
 Sedation / Analgesia: Dexmedetoimidine, Fentanyl
 Pulmonary: Ipratropium
 Nitrogen washout testing preformed
ICU Day 2
ICU COURSE ~ CULTURES
 (+) S. epidermidis from both aerobic bottles
pansensitive except to PCN
 (+) M. pneumonia IgG Ab & IgM Ab
 (+) CMV
 Nasal / Sputum
 (-) Influenza A & B PCR
 (-) RSV
 Bronchial wash: normal respiratory flora, (-)
pneumocystis
 Negative Cultures:







Anaerobic bottles at 48 hours
Legionella pneumophila
AFB, acid-fast
MRSA
Viral
Candida
Alpha-1-Antitrypsin deficiency mutation
 Stool:
 (-) Clostridium difficile toxin A & B
ICU COURSE
 Transferred to ICU / oncology unit at NYU where he
received care, including monoclonal antibody therapy
 Remained intubated, with mild improvement in lung
function
 Dr Llobet confirmed masses seen on CT were not on a CT scan
from 1 month earlier
 Continued on vasopressors, sedation, antivirals, antibiotics
and pulmonary medications throughout his stay
 Discharge diagnoses:
 Respiratory failure secondary to:
 Pneumonia with possible empyema
 Metastatic synovial cell sarcoma with space-occupying lung
masses
 Immune-mediated pneumonitis / interstitial lung disease
ICU Day 3
SYNOVIAL CELL SARCOMA
BACKGROUND
 Soft tissue sarcomas are a heterogeneous group of rare
mesenchymal tumors which include synovial cell sarcomas
 Malignant precursor cells differentiate along muscle, adipose,
fibrous, cartilage, nerve, or vascular tissue
 Arise in limbs, thorax, head, neck, abdominal cavity,
retroperitoneum
 Improved survival improved due to early / radical surgery,
along with radiation
Tumorlibrary.com
EPIDEMIOLOGY
 Incidence 2.75 per 100,000
 ~800 new cases in US annually
 Male:Female 1:1 prevalence
 5-10% of all soft-tissue sarcomas
 Generally presents at a younger age than other soft
tissue sarcomas
 3rd most common soft-tissue tumor in adolescents & young adults
 1/3 cases diagnosed in those under 20 years of age
 Mean age at diagnosis ~30 years of age
Tumorlibrary.com
SYNOVIAL CELL SARCOMA
CELL ORIGIN
 Not associated with synovium, rather
undifferentiated mesenchymal cells
 Named for similarity between tumor cells & primitive
synoviocytes
 Neurologic origin suggested due to histologic
resemblance between neural cells of
malignant peripheral nerve sheath tumor &
synovial cell sarcomas
Stem Cell Reviews and Reports. March 2011, Volume 7, Issue 1, pp 32-42
SARCOMA METASTATIC DISEASE
 Occurs most often in para-articular regions,
though can arise from tendon sheaths,
bursae or joint capsules
 Primary metastatic site is pulmonary
 Extrapulmonary metastases to local bones, fascial
planes / soft tissue, spine, paraspinous tissues
 Hematogenous or lymphatic dissemination rare but
life-threatening
 Retroperitoneal & visceral sarcomas primarily
metastasize locally or hepatically
www.spandidos-publications.com
PRESENTATION
 Usually occurs within the 1st three decades with patients
being symptomatic months to years prior to diagnosis
 HPI: small, painful nodule rapidly increasing in size
 80% occur in extremities, 70% in lower limbs
 Popliteal fossa most common, followed by hands / feet, though
affects entire appendicular skeleton
 Most sarcomas intermuscular, found within 5 cm of a joint
 Intra-articular origin <10 % of cases
PLAIN RADIOGRAPHS
 Normal in ~50%
 Spotty / irregular calcifications
(“snowstorm”) within soft tissue
matrix in a peripheral distribution
 10-20% show periosteal reaction,
bony erosion or invasion
Tumorlibrary.com
COMPUTED
TOMOGRAPHY
 Confirm presence of mass, describe size
& location, but non-diagnostic
 Often detects secondary bony
involvement or metastatic spread prior
to identification of primary lesion
posterng.netkey.at; J Korean Surg Soc. 2012 Dec;83(6):403-407
MAGNETIC RESONANCE IMAGING
 Diagnostic test of choice
 Low signal intensity (T1) vs high signal intensity (T2-weighted)
 “Triple Signal Intensity Sign”




Pathognomonic (30-50%)
Hypointense, isointense & hyperintense with fat on T2–weighted
Matrix signal homogeneous unless calcifications present
With contrast enhancement appears heterogeneous with nodular
enhancement & cysts
 Often mistaken for ganglion cysts
Tumorsurgery.org
SAGITTAL T2 WEIGHTED
AXIAL T2 WEIGHTED
Tumorsurgery.org
DIAGNOSTIC IMAGING COMPARISONS
radiologycases.com; roentgenrayreader.blogspot.com
HISTOLOGY / GROSS
PATHOLOGY
 Appearance similar to other round blue cell tumors
 Circumscribed, round or multilobed
 May grow to >15 cm, but average 3-5 cm diameter
 Less differentiated variants grow rapidly, are poorly
circumscribed, have multiple areas of hemorrhage, necrosis &
cystic formation
 Macroscopically, yellow to gray-white & “greasy”
 Three types of synovial sarcoma:
 Monophasic, Biphasic, Poorly Differentiated
www.kjim.org; tumorsurgery.org
MICROSCOPIC PATHOLOGY ~
TWO CELL TYPES
SPINDLE CELL
Small, uniform & ovoid cells with
pale nuclei & sparse cytoplasm
EPITHELIOID CELLS
Ovoid nuclei & abundant cytoplasm
MONOPHASIC
 Types:
 Fibrosarcoma, leiomyosarcoma, epithelioid, clear cell
 Monophasic Fibrous:
 Predominantly spindle cells mixed with round cells
 Arranged in fascicles, poorly defined cytoplasm
without glandular areas
 Monophasic Epithelial:
 Difficult to differentiate from adenocarcinoma
BIPHASIC
 Types:
 Malignant peripheral nerve sheath, carcinoma, diffuse
type tenosynovial giant cell tumor
 Columnar epithelial & spindle-cell components in
equal proportions
 Round cells & spindle-shaped fibroblasts alternate with
glandular-like areas lined by mucin-containing synoviallike cells
POORLY DIFFERENTIATED
 Types:
 Malignant peripheral nerve sheath tumor, fibrosarcoma,
hemangiopericytoma, Primitive peripheral neuroectodermal
 High grade round cell tumor with dense cellularity,
numerous mitoses, necrosis & punctate calcifications
 Histologically graded by mitotic activity plus necrosis:
 Grade 1 (differentiated) to grade 3 (poorly differentiated)
 Immunohistochemically positive for vimentin, cytokeratin, or
epithelial membrane antigen
LABORATORY STUDIES
 Histology & molecular diagnostic testing diagnostic
 90% have translocation & fusion between chromosomes 18
SYT gene & short arm of chromosome X SSX gene
 t(X;18)(p11;q11) with variants SYT-SSX1, SYT-SSX2, or SYT-SSX4
 Reverse transcriptase-PCR 96% sensitive, 100% specific
 Fluorescence in situ hybridization (FISH) less expensive than RT-PCR
but with a lower sensitivity
SURGICAL
MANAGEMENT
 Excision is cornerstone of treatment
 Careful preoperative staging crucial as resection of
isolated metastases increases survival if primary
tumor well controlled
 Palliative surgery appropriate, particularly to
alleviate pain or achieve hemorrhage control
Tumorsurgery.org
SURGICAL MANAGEMENT
 Surgical approach plans for a wide / radical
resection
 Amputation required in 20% of patients due
to required tumor-free margin of 1-3 cm
Tumorsurgery.org
RADIATION THERAPY
 Preoperative radiation therapy associated with poor
wound healing, though often recommended to reduce
tumor size
 Post-operative radiation recommended, particularly if
margins close to vital neurovascular structures
 External-beam radiation (40-60 Gy) directed at tumor site &
surrounding normal tissue margins
 Vital neurologic structures, open physes, or extreme peripheral
location increase complications
 Alternatives are brachytherapy & / or intensity-modulated
radiation therapy (IMRT)
aapm.org
MEDICAL THERAPY
 Chemotherapy as adjuvant or neoadjuvant treatment to post-operative radiotherapy
does not increase survival or disease control unless primary tumor >5cm, but may
improve months of survival
 Granulocyte colony-stimulating factor (G-CSF) added to any chemotherapy stimulates
healthy marrow growth
 Clinical trials:
 Promising results with a murine monoclonal antibody that attacks frizzled homologue cell-surface
receptor (FZD10), present only in sarcoma cells
 Innovative SYT-SSX–derived peptide vaccine in phase 2 trials
Uptodate.com
OPDIVO® (NIVOLUMAB)
 Patient undergoing Opdivo (nivolumab) therapy for unresectable sarcoma
 Acute pneumonitis / interstitial lung disease thought be a result of Opdivo, contributing to acute
respiratory failure & susceptibility to sepsis
 Opdivo is a human monoclonal antibody that blocks interaction between PD-1 & it’s
ligands PD-L1 / PD-L2
 Indicated for treatment of unresectable metastatic melanoma, advanced sarcoma, non-small cell
carcinoma, or disease progression after platinum-based chemotherapy (i.e. ipilimumab / Yervoy®)
 Given as single agent, or with ipilimumab , a monoclonal antibody targeting CTLA-4 protein receptors,
allowing cytotoxic T lymphocytes to recognize & destroy cancer cells
 Combined nivolumab & ipilimumab results in enhanced T-cell function greater than the effects
of either antibody alone
OPDIVO® (NIVOLUMAB)
MECHANISM OF ACTION
 Inhibits binding of PD-1 ligands to T cell PD-1
receptors, inhibiting T-cell proliferation &
cytokine production resulting in decreased
tumor growth
 PD-1 ligand upregulation contributes to
inhibition of active T-cell tumor immune
surveillance
Opdivohcp.org
OPDIVO® (NIVOLUMAB)
PHARMACOKINETICS
 No specific contraindications other than pregnancy,
breast-feeding, & development of specific adverse
reactions
 Weight-based dosing
 3 mg/kg IV over 60 minutes every 2 weeks until disease progression
or unacceptable toxicity
 Half-life: 25 days
 Mean clearance 10 mL/hr
 No effect on the clearance for age, gender, race, tumor size / type,
LDH, PD-L1 expression, renal or hepatic impairment
discovermedicine.com
 No drug-drug interaction studies conducted
OPDIVO® (NIVOLUMAB) SIDE
EFFECTS ~ ALL “IMMUNE MEDIATED”
 GI:
Colitis, hepatitis, bloody diarrhea, weight loss, jaundice, constipation, N/V
 HEENT:
Sclera injection, photophobia, dacrocystitis, oral ulcers, deepening of voice
 CV:
Tachyarrhythmia, bradyarrythmia, ischemia
 MS:
Back pain, “bone” pain, muscle cramps
 Endo:
Hypo/ hyperthyroid, edema, fatigue, heat / cold sensitivity, diaphoresis
 Renal:
Nephritis, AKI / ARF, hematuria
 Skin:
Dermatitis, blistering, hair loss
 CNS / PNS:
Encephalitis, diplopia, dizziness / vertigo, syncope, persistent headache
 Psych:
Depression / anxiety, insomnia, night sweats
 Pulmonary: Pneumonitis, interstitial lung disease, respiratory distress,
thickening of bronchial secretions, persistent cough
OPDIVO® (NIVOLUMAB)
ASSOCIATED PNEUMONITIS
 By FDA definition the immune-mediated pneumonitis must have no clear etiology other
than the PD1-inihibtor therapy & require use of corticosteroids
 Immune-mediated pneumonitis & / or interstitial lung disease are adverse effects of all PD1inhibitor therapies
 Median time to pneumonitis development after initiating treatment is 5 months
 In one phase 2 trial, pneumonitis was a common “life-threatening” adverse event, occurring
in 5% of all patients3
 In two recent phase 3 trials, the incidence of pneumonitis was 1.5%1 & 1.9%2
 Across clinical trials in 1590 patients with solid tumors, fatal immune-mediated pneumonitis
occurred in 0.3% (5/1590) of patients receiving nivolumab as a single agent
1NEJM. 2015;372:320-330; 2Lancet Oncol. 2015;16:375-384; 3Lancet Oncol. 2015;16:257-265
PNEUMONITIS CLINICAL GRADING
SYSTEMS
Group
Grade 1
Grade 2
Grade 3
Grade 4
South-West
Oncology Group
Radiographic changes;
symptoms do not
require steroids
Steroids required, or
pleurocentesis of pleural
effusion
O2 required
Requires assisted
ventilation
Radiation Therapy
Oncology Group
Mild symptoms of dry
cough or DOE
Persistent cough requiring
narcotic or antitussives;
dyspnea with minimal
efforts but not at rest
Severe cough
unresponsive to
antitussives; dyspnea at
rest, clinical / radiologic
evidence of acute
pneumonitis; O2 or
steroids required
Severe respiratory
insufficiency, continuous
O2 or assisted
ventilation
National Cancer
Institute
Asymptomatic,
radiographic findings
only
Symptomatic, but not
interfering with ADLs
Symptomatic, interferes
with ADLs, O2 required
Life-threatening;
ventilatory support
indicated
Semin Oncol 32(Suppl 3): S42-S54. Int J Radiation Oncology Biol Phys. 63(1):5-24
OPDIVO® (NIVOLUMAB)
ASSOCIATED PNEUMONITIS
 Management:
 High-dose systemic corticosteroids (>40 mg
prednisone or equivalent / day) followed by a taper
 Temporarily withhold nivolumab in moderate
(grade 2) pneumonitis
 Permanent discontinuation in severe (grade
3) or life-threatening (grade 4) pneumonitis
 Pneumonitis led to discontinuation of PD-1 inhibitor
in 1% all patients
 In one study, symptoms completely resolved in 7 of
9 patients with grade 2 or 3 pneumonitis1
Low-power image showing interstitial pneumonia and
necrosis with areas of hemorrhage. www.captodayonline.com
1NEJM. 2015;372:320-330
SYNOVIAL CELL SARCOMA
PROGNOSIS
 After metastases, disease stabilization viewed
as a realistic end point as essentially incurable
 Median survival after distant metastases 11-15 months
with 25% 2-3 year survival
 In selected patients, resection of pulmonary metastases
increases 5 year survival to 25-40%
 Prognostic factors for prolonged survival differ
from those predicting chemotherapy response,
suggesting survival more dependent upon
disease biology than treatment
 In metastatic unresectable disease, systemic
therapy provides symptom palliation, slows
progression, & may prolong survival
Survival curves for primary sites based upon data from 3677
patients with STS treated at Sloan-Kettering 1982-2001.
Borden EC, et al. Soft tissue sarcomas of adults: State of the
translational science. Clin Cancer Res 2003; 9:1941.
PROGNOSIS
Outcome predicted by: Tumor size, Anatomic localization, Histologic grade
POOR PROGNOSIS
 Poorly differentiated histology
 Recurrence
 Male gender
 Metastases at presentation
 25% 2 year survival
 Bone or neurovascular invasion
 Proximal extremity or truncal tumor location
GOOD PROGNOSIS
 Biphasic histologic pattern
 SYT/SSX2 fusion genes
 Hand or foot location
 Size < 5 cm
 Female gender
 Age < 50 years
 Negative resection margins
SYNOVIAL SARCOMA PROGNOSIS
 In a recent study, 60% patients
responding to Opdivo were still
responding six months later
Study of nivolumab in subjects with advanced or
metastatic squamous cell non-small cell lung
cancer who have received at least two prior
systemic regimens (CheckMate 063). Accessed
December 2015.
CASE FOLLOW-UP
 Patient transferred to NYU on Day….of his ICU stay
WILL FILL IN THIS SLIDE
WHEN I CLARIFY DETAILS
ON MONDAY
ADDITIONAL REFERENCES

Images: Tumorsurgery.org, Wikipedia, Google, Bing, Medline image searches

Lessnick SL, Dei Tos AP, Sorensen PH, Dileo P, Baker LH, Ferrari S, et al.

Eilber FC, Dry SM. Diagnosis and management of synovial sarcoma. J Surg Oncol. 2008 Mar 15. 97(4):314-20.

Bergh P, Meis-Kindblom JM, Gherlinzoni F, Berlin O, Bacchini P, Bertoni F, et al. Synovial sarcoma: identification
of low and high risk groups. Cancer. 1999 Jun 15. 85(12):2596-607.

Spira AI. The use of chemotherapy in soft-tissue sarcomas. Oncologist. 2002. 7(4):348-59.


Zagars GK, Ballo MT, Pisters PW, Pollock RE, Patel SR, Benjamin RS, et al. Prognostic factors for patients with
localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225
patients. Cancer. 2003 May 15. 97(10):2530-43.
Sakabe T, Murata H, Konishi E, Takeshita H, Ueda H, Matsui T, et al. Evaluation of clinical outcomes and
prognostic factors for synovial sarcoma arising from the extremities. Med Sci Monit. 2008 Jun. 14(6):CR305-310.

Mazeron JJ, Suit HD. Lymph nodes as sites of metastases from sarcomas of soft tissue. Cancer. 1987 Oct 15.
60(8):1800-8.
Deshmukh R, Mankin HJ, Singer S. Synovial sarcoma: the importance of size and location for survival. Clin
Orthop Relat Res. 2004 Feb. 155-61.

Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective
randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol. 1996 Mar. 14(3):859-68.
Ladenstein R, Treuner J, Koscielniak E, d'Oleire F, Keim M, Gadner H, et al. Synovial sarcoma of childhood and
adolescence. Report of the German CWS-81 study. Cancer. 1993 Jun 1. 71(11):3647-55.

Stefanovski PD, Bidoli E, De Paoli A, Buonadonna A, Boz G, Libra M, et al. Prognostic factors in soft tissue
sarcomas: a study of 395 patients. Eur J Surg Oncol. 2002 Mar. 28(2):153-64.
Kawai A, Woodruff J, Healey JH, Brennan MF, Antonescu CR, Ladanyi M. SYT-SSX gene fusion as a determinant
of morphology and prognosis in synovial sarcoma. N Engl J Med. 1998 Jan 15. 338(3):153-60.

Spillane AJ, A'Hern R, Judson IR, Fisher C, Thomas JM. Synovial sarcoma: a clinicopathologic, staging, and
prognostic assessment. J Clin Oncol. 2000 Nov 15. 18(22):3794-803.

Thompson RC Jr, Garg A, Goswitz J, Cheng EY, Clohisy DR, Dusenbery K. Synovial sarcoma. Large size predicts
poor outcome. Clin Orthop Relat Res. 2000 Apr. 18-24.

Ten Heuvel SE, Hoekstra HJ, Suurmeijer AJ. Diagnostic accuracy of FISH and RT-PCR in 50 routinely processed
synovial sarcomas. Appl Immunohistochem Mol Morphol. 2008 May. 16(3):246-50.

www.uptodate.com. “Soft Tissues Sarcoma”, Synovial Cell Sarcoma”, “Opdivo”. Accesed Dec 2015

N Engl J Med. 2015;373:288-290




Kind M, Stock N, Coindre JM. Histology and imaging of soft tissue sarcomas. Eur J Radiol. 2009 Oct. 72(1):6-15.

Judson I, et al. Lancet Oncol 2014; 15:415. Accessed online December 2015.

Mesna tablets. United States Prescribing Information. US National Library of Medicine. (Available online at
dailymed.nlm.gov, accessed May 13, 2014)

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer
V.2.2016. © 2015 National Comprehensive Cancer Network, Inc. All rights reserved. Accessed December 2015
SUMMARY
 Multidisciplinary review of a oncological process with an rare
Reminder….
complication with significant
impacts on management of critically ill
patients
Grand Rounds will be every other month until final
 Review of the indications for mechanical ventilation
ACCME CME Approval
 Review of a novel monoclonal antibody agent with significant side
effects February ~ Focusing on a Surgical Case