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2 Percutaneous or open surgical biopsy in NB? Recommendations for percutaneous needle biopsy Claudio Granata Istituto Giannina Gaslini (Genova, Italy)

3 Biopsy in NB Which case? Unresectable NB Why? To collect sufficient material for Histology Biologic studies (MYCN, 1p-del,...) How? Open biopsy Laparo / Thoracoscopic biopsy Image guided core needle biopsy

4 Ideal technique of biopsy Effective Safe Easy Suitable for all lesion Minimally invasive Repeatable Cheap

5 Effective Surgical Biopsy Recommended in most protocols Invasive Possible spillage Expensive Complications?

6 Laparoscopic biopsy Less invasive than open biopsy Not suitable for all lesions Possible spillage Conversion to open surgical biopsy relatively frequent Higher rate of complications with thoracoscopy Expensive

7 Image guided core needle biopsy (IGCNB) Adequacy? Accuracy? Complications? Minimally invasive Cheap

8 IGCNB: technique Imaging technique US whenever possible CT when necessary Coaxial technique advisable Multiple passes and cores with a single puncture 16G/18G semiautomated needle Retroperitoneal approach

9 Materials

10 Biopsy planning

11

12 IGCNB: theoretical disadvantages Unrepresentativeness Sample too small for: formal morphological studies molecular studies

13 Unrepresentativeness? IGCNB 4 µm, area 10 mm 2 0,0001 % of mass Open Biopsy 4 µm, area 100 mm 2 0,001 % of mass vs assume 5 cm diameter mass Adapted from NJ Sebire, GOSH, 2007

14 GN and nodular GNB Nodular GNB difficult to diagnose with IGCNB GN on needle biopsy may be nodular GNB Single No Nodule? Multiple Primary site Metastatic site

15 Too small for molecular studies? Historical issue Now: RT/PCR (requiring only 30 ngr of tissue) FISH (dabs imprints only) Immunostaining (from a single 0.5 mm slice µm sections)

16 Too small for morphological studies? Historical issue Traditional hystopathological features seem not to have an independent effect on prognosis of NB Biological molecular studies (MYCN amp, 1p del,...) have proved to be of much more prognostic value NJ Sebire, Med Hypotheses, 66: , 2006

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18 Methods Computer based search of articles on IGCNB in children with suspected neoplasms Review of pooled data to define adequacy, accuracy and complications Results Review of 13 studies for a total of 698 IGCNB Adequacy of biopsies: 94% Accuracy of biopsies: 94% Complications: 1% No needle tract recurrence observed

19 IGCNB: results 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Histology FISH RTPCR Freeze Cytology 100 consecutives cases at GOSH NJ Sebire, GOSH, 2007

20 Conclusions In most cases IGCNB is adequate for diagnosis, prognostication, molecular studies and research in pediatric tumors Results are comparable with those of surgical techniques Specialist interventional radiologists, laboratory staff, and pediatric pathologists are required to get maximum information from such samples

21 Ultrasound-guided core needle biopsy of primary liver tumours in young children Derek Roebuck Great Ormond Street Hospital London, UK

22 Primary liver tumours in children is biopsy necessary? what technique should be used? image-guided needle biopsy laparoscopic biopsy laparotomy / minilaparotomy how safe is biopsy? how accurate is biopsy?

23 Biopsy may not be necessary if diagnosis is likely on the basis of imaging, and management is: primary resection conservative (serial ultrasound) if biochemical tests are diagnostic certain patients with hepatoblastoma??

24 International approaches USA Japan attempt resection chemotherapy SIOPEL percutaneous biopsy chemotherapy delayed surgery

25 Possible compromise PRETEXT I easy PRETEXT II up front resection chemotherapy all others percutaneous biopsy chemotherapy delayed surgery

26 Further refinement all others age 6 months to 3 years and AFP elevated and imaging = hepatoblastoma no yes percutaneous biopsy chemotherapy delayed surgery

27 Benefits of biopsy material for biological studies protection of doctors increased confidence for parents

28 Coaxial plugged image-guided needle biopsy

29 Biopsy technique biopsy path chosen carefully avoid peritoneal surface cross only disposable liver segments ultrasound guidance high-frequency transducer plugged coaxial biopsy semi-automated cutting needle

30 Biopsy path MHV LPV 4 8 IVC

31 Coaxial biopsy technique

32 freehand ultrasound guidance

33

34

35 Results of this technique at Great Ormond Street

36 Methods prospective study of US-guided biopsy in children aged less than 5 years safety assessed by clinical follow-up accuracy assessed by comparison of biopsy result with final diagnosis resection specimen clinical follow-up

37 Patients 33 children (20 male) median age 11 months youngest 14 days oldest 4 years median follow-up 4.5 yr

38 Tumour characteristics multifocal 7/33 (21%) maximum diameter 170 mm median volume 650 ml

39 Needle size 18 gauge 21% 14 gauge 3% 16 gauge 76%

40 Complications one drop in haemoglobin level without imaging evidence of haemorrhage no evidence of tumour seeding

41 Accuracy 30/33 (91%) biopsy diagnosis accurate 2/33 (6%) biopsy diagnosis accurate when combined with clinical findings 1/33 (3%) final diagnosis unclear overall 32/33 (97%) accurate diagnosis

42 Final diagnoses hepatoblastoma = 21 (66%) haemangioma = 4 (12%) other = 7 (22%) malignant = 3 benign = 4

43 Discussion

44 Safety no haemorrhage no needle tract seeding small numbers at least as good as open biopsy

45 Accuracy small numbers make generalization unreliable 97% in this series probably as good as open biopsy

46 Conclusions small numbers make generalization potentially unreliable ultrasound-guided biopsy of primary liver tumours is acceptably safe and accurate needle biopsy is preferable to surgical biopsy (SIOPEL)

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54 Percutaneous US or CT guided lung biopsy vs. needle localization for thorascopic resection Fredric Hoffer MD FAAP, FSIR Pediatric Interventional Radiologist Children s Hospital University of Washington, Seattle

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56 Guidance methodologies Percutaneous lung nodule biopsy US guidance CT-Guide 1010 (Ultraguide Inc. formerly from Lakewood, CO and Tirat Hicarmel, Israel) CT in room sectioning (Smart Step, GE Healthcare, Milwaulkee, WI) Needle localization for surgical resection Prior CT or Intraoperative US

57

58 CT Guide (UltraGuide( Inc.)

59 Actual biopsy needle: Result: Hodgkin disease

60 Biopsy Methods Coaxial sheath needle often used Spring loaded core biopsy needles: 15G for tumors 18G for liver 20G for lung Multiple samples: median 5

61 Sheath & spring loaded needle

62 Specimen submission for solid tumors 10% formalin: 2+ cores for Histopathology including Immunohistochemical staining RPMI 1640:2 cores each for PCR for typical solid tumor translocations FISH for NMYC for neuroblastoma DNA index for neuroblastoma Cytogenetics for rare tumors

63 Polymerase Chain Reaction (PCR): molecular pathology Ewing sarcoma Family of Tumors (ESFT) t(11;22), t(21;22) Rhabdomyosarcoma (RMS) t(2;13) Synovial cell sarcoma t(x;18)

64 St. Jude Results 202 solid tumor biopsies: 105 for initial Dx; 97 for recurrence 121 TP, 67 TN, 14 FN, 0 FP Sensitivity 90% Specificity 100% Accuracy 93%

65 Biopsy of recurrent disease 97 percutaneous biopsies 56 TP, 29 TN, 12 FN Sensitivity 82% Specificity 100% Accuracy 88% The lower sensitivity probably due to small needle size, number of passes, tumor size and frequent metastatic lung nodule biopsy

66 Biopsy of lung to rule out solid tumor Cancer 104: ; 652; biopsies of the lung 21 to detect recurrence 19/20-G sheath/core biopsy needle 7 guided by CT using Smart Step 6 by CT using CT-Guide by CT alone 3 by US alone 2 by combined CT and US

67 Results of the 21 lung biopsies performed to rule out recurrence 12 nodules > 1 cm LD: 7 TP, 5 TN for malignancy 100% accuracy 9 nodules < 1cm (range, cm) 5 FN, 2 TP, and 2 TN 44% accuracy Cancer 104: ; 2005.

68 Results per modality The 2 US guided biopsies were accurate, but of large pleura based lesions The 19 biopsies using CT guidance had 7 TP, 7 TN and 5 FP (74% accuracy) Cancer 104: ; 2005.

69 Complications of biopsy of lung or mediastinum to rule out solid tumor Pneumothorax in 3 of 34 cases (9%) All minor None required a chest tube One warranted hospital admission for observation

70 Lung biopsy of pleural based lesions using US guidance Pediatr Radiol Jun;36(6): % success rate 44% minor complications Size of the pleural surface unrelated to technical success (P=0.106) or the incidence of complications (P=0.23) Adequate technique for lesions with > 5mm pleural contact

71 Diagnosis of leukemia & lymphoma Bone marrow biopsy Fluid aspirate Percutaneous biopsy 6 passes 14/15G sheath/spring loaded needle Suspected NHL or recurrent leukemia Permanent sections B5, 10% formalin Flow cytometry Hanks or RPMI 1640 Cytogenetics RPMI /- PCR balanced NS Suspected Hodgkin disease Permanent sections

72 Hematologic malignancies (Hodgkin lymphoma, NHL, leukemia) Materials: 4-year period, 22 patients Methods: 25 percutaneous biopsies: 16 TP, 3 TN, & 6 FN 6 fluid aspirations & 3 catheter drainages: 8 TP & 1 FN 1 needle localization: FN Overall results Sensitivity 75% Specificity 100% Accuracy 77%

73 Pulmonary complications of biopsies of hematologic malignancies 1 transient hypoxia 2 slight bleeds 1 hemo-pneumothorax required immediate chest tube with possible tumor spread (died of malignant pleural effusion a year later)

74 NHL: airway & SVC obstruction

75 Aspirate of pleural effusion may be diagnostic

76 NHL by mediastinal biopsy after non-diagnostic thoracentesis

77 Presumed Hodgkin lymphoma

78 Reed Sternberg cells not seen on 15G, 7 pass percutaneous biopsy

79 Recurrent Hodgkin disease diagnosed with 20G needle

80 Indications Needle localization Resection of subpleural nodule at thorascopy Resection of small soft tissue mass Technique Same anesthesia as resection Kopans needle (Cook, Inc) 0.1 to 0.2 cc of methylene blue in lung J Pediatr Surg 32:1624-5, 1997 Pediatr Radiol 30: , 2000

81 Methylene blue without hooked wire J Pediatr Surg 37:970-3, thorascopic procedures completed successfully. 12 yielded diagnostic pathologic material 7 offered therapeutic resections. All chest tubes removed within 36 hours.

82 Methylene blue-stained autologous blood for needle localization and thorascopic resection of deep pulmonary nodules J Pediatr Surg 37: , ml autologous blood stained with 0.3 ml methylene blue All 19 resections diagnostic 80% malignancy LD mean 0.9 cm (range, 0.3 to 3 cm) Pulmonary Depth mean 0.8 cm ( ) 40% chest tubes 53% were discharged home the same day

83 Kopans 20G needle & hooked wire

84 Needle localization of rhabdomyosarcoma metastasis

85 CT guide used for needle localization

86 On target

87 Alternative surgical techniques Thoracoscopic localization techniques for patients with solitary pulmonary nodule: radioguided surgery versus hookwire localization. J Cardiovasc Surg 47:355-9, 2006 Ultrasonographic localization of occult pulmonary nodules during video-assisted thoracic surgery. Eur Radiol 13: , 2003

88 Summary: Pulmonary nodules For diagnosis Percutaneous biopsy CT with in room monitoring, realtime CT or breath-hold technique (e.g. anesthesia & paralysis) US for pleural based nodules > 5 mm Needle localization and thoracoscopic removal For therapy US guided thorascopic resection Thoracotomy RF ablation

89 Starting an image-guided guided biopsy protocol in a paediatric hospital The AMC experience. Rick R. van Rijn. MD. PhD. Emma Children s hospital Academic Medical Centre Amsterdam The Netherlands

90 First case I did Female, 16 year Medical history: Hodgkin disease. Mediastinal mass on CXR.

91 easy procedure 8-16G tru-cut biopsy cores No complication Result of the biopsy

92 easy procedure Unknown for days Biopsy material lost in pathology department Finally found Still diagnostic Hodgkin lymphoma

93 Don t trust existing procedures

94 Cases to date

95 Cases to date FNA Biopsy 22 11

96 Cases to date FNA Biopsy Diagnostic 17 6 Non-diagnostic 5 5

97 Non diagnostic biopsies Lymph node Lost in pathology department Lymphoma Soft-tissue tumor leg PNET Renal? Nefroblastoma/nefroblastomatosis Abdominal metastasis Fully necrotic

98 However.. There have been many more. Many at the OR. Surgery coding. No OR code for radiologist. Many different codes in use.

99 Develop a database - independent of the hospital system

100 Pathology reports Some excerpts: Several small slithers of tissue Some small pipes of tissue Hardly any material Damaged tissue Material from unknown location Not representative!

101 Get the pathologist in on the game

102 Children aren t small adults Anesthesia in many cases necessary Get the anesthesiologists to like you OR capacity can be problematic Delay of procedure Problematic planning Disruption of radiology planning

103 Be available at any time

104 Example: Rhabdomyosarcoma EpSSG RMS 2005 Open biopsy is recommended and should be incisional although US and CT guided core needle biopsies may be appropriate in difficult or inaccessible sites No reference to PIR studies!

105 Get involved with protocols

106 Conclusion Don t trust existing procedures Develop a database independent of the hospital system Get the pathologist in on the game Be available at any time Get involved with protocols