TUGAS MATA KULIAH

ILMU BEDAH KHUSUS VETERINER

“Teknik Operasi Biopsi pada Pankreas”

Oleh:
Kelompok D5

Ni Luh Risna Cahyani 1609511111

Derisna Sawitri Ungsyani 1609511112
Elizabeth Kezi Damayanti 1609511124
Makrina Weni Misa 1609511125
Kelas: 2016D

Laboratorium Bedah Veteriner

Fakultas Kedokteran Hewan
Universitas Udayana
Tahun 2019

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 RINGKASAN

Biopsi merupakan suatu tindakan diagnostik yang dilakukan dengan mengambil

sampel jaringan atau sel untuk dianalisis di laboratorium, baik untuk mendiagnosis
suatu penyakit atau untuk mengetahui jenis pengobatan atau terapi yang terbaik
bagi pasien. Tujuan utama melakukan biopsi adalah untuk menegakkan diagnosis,
untuk mengevaluasi perjalanan penyakit, dan untuk mengonfirmasi data klinis
dengan keadaan histopatologi organ. Biopsi pada pankreas dilakukan apabila
dicurigai adanya ganguan atau penyakit pada pankreas. Biopsi pankreas dapat
dilakukan pada keadaan hewan yang mengalami pankreatitis akut dan kronis serta
neoplasma. Ada beberapa hal yang perlu diperhatikan dalam biopsi pada pankreas,
diantaranya preoperasi, prosedur operasi, dan perawatan setalah operasi. Preoperasi
dilakukan dengan menyiapkan instrument, mempersiapkan pasien, dan
mempersiapkan operator. Prosedur biopsi pada pankreas memiliki beberapa metode
yaitu brush biopsy, Fine Needle Aspiration (FNA) biopsy dan Endoscopic
Ultrasound (EUS), serta laparoskopi. Biopsi pada pankreas dapat menfasilitasi
diagnosis gangguan patologi anatomi pada pankreas.

Kata Kunci: diagnostik, biopsi, pankreas

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 SUMMARY

Biopsy is a diagnostic procedure performed by taking samples of tissues or cells for

analysis in the laboratory, either to diagnose a disease or to determine the type of
treatment or therapy that is best for the patient. The main purpose of the biopsy is
to establish a diagnosis, evaluate the course of the disease and confirm the clinical
data on the histopathological status of the organ. Pancreas biopsy is performed
when there is suspicion of a disorder or disease in the pancreas. Pancreatic biopsy
can be performed in animals with acute or chronic pancreatitis and neoplasms. A
pancreas biopsy must consider a number of factors, including preoperative surgery,
surgical procedures, and treatment after surgery. Preoperative surgery consists of
preparing the instruments, preparing the patients and preparing the operators. The
pancreatic biopsy procedure has several methods, namely brush biopsy, fine needle
aspiration biopsy (FNA) and endoscopic ultrasound (EUS) and laparoscopy.
Pancreatic biopsy can facilitate the diagnosis of anatomical pathological
abnormalities of the pancreas.

Keyword: diagnostic, biopsy, pancreas

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 KATA PENGANTAR

Puji syukur kami panjatkan kehadirat Tuhan Yang Maha Esa, karena kami
dapat menyelesaikan tugas mata kuliah Ilmu Bedah Khusus Veteriner “Teknik
Operasi Biopsi pada Pankreas” ini tepat pada waktunya. Terima kasih penulis
ucapkan kepada semua pihak yang telah memberikan dukungan dan sumbangan
materi demi makalah ini.
Kami menyadari, makalah sederhana ini masih banyak kekurangannya,
tetapi kami berharap agar makalah kami ini dapat memenuhi tugas matakuliah Ilmu
Penyakit Bakteri dan serta bermanfaat untuk pembaca sekalian. Kami juga
menerima kritik serta saran yang diberikan. Akhir kata, kami selaku penulis ingin
mengucapkan banyak terima kasih kepada pembaca.

Denpasar, 1 Oktober 2019

Penulis

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 DAFTAR ISI
HALAMAN JUDUL...........................................................................................i
RINGKASAN .....................................................................................................ii
SUMMARY ........................................................................................................iii
KATA PENGANTAR .......................................................................................iv
DAFTAR ISI ......................................................................................................v
DAFTAR GAMBAR .........................................................................................vi
BAB 1. PENDAHULUAN
1.1 Latar Belakang ....................................................................................1
1.2 Rumusan Masalah ...............................................................................1
BAB 2. TUJUAN DAN MAFAAT PENULISAN
2.1 Tujuan Penulisan .................................................................................2
2.2 Manfaat Penulisan ...............................................................................2
BAB 3. TINJAUAN PUSTAKA
3.1 Pankreas ...............................................................................................3
3.2 Biopsi ...................................................................................................3
3.3 Biopsi pada Pankreas ...........................................................................4
3.4 Kegunaan Biopsi pada Pankreas..........................................................5
BAB 4. PEMBAHASAN
4.1 Pre-operasi Biopsi pada Pankreas ........................................................6
4.2 Prosedur Biopsi pada Pankreas ............................................................8
4.3 Perawatan Setelah Biopsi pada Pankreas ............................................12
BAB 5. PENUTUP
5.1 Kesimpulan .........................................................................................14
5.2 Saran ...................................................................................................14
DAFTAR PUSTAKA ........................................................................................15
LAMPIRAN

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 DAFTAR GAMBAR

1. Gambar 4.1. Instrumen bedah untuk biopsi pada pankreas ..........................6

2. Gambar 4.2. Ringkasan skemaris dari teknik FNA.......................................9
3. Gambar 4.3. Gambaran EUS pada pankreas adanya 3,1 cm pancreatic
adenocarcinoma pada ujung pankreas ..........................................................10
4. Gambar 4.4. Posisi pasien dorsal recumbency .............................................10
5. Gambar 4.5. Prosedur pemasukan trocar atau kateter melalui insisi di
abdomen ........................................................................................................11
6. Gambar 4.6. Penggunaan probe untuk merektrasi duodenum agar pankreas
lebih terlihat ..................................................................................................12
7. Gambar 4.7. Penggunaan clamshell biopsi forceps digunakan untuk
mengambil sampel ........................................................................................12

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BAB 1
PENDAHULUAN

1.1. Latar Belakang

Biopsi berasal dari kata “bios” yang artinya hidup dan “opsis” yang artinya
melihat, jadi biopsi adalah mengambil sepotong jaringan yang masih dalam
keadaan hidup dan memeriksa secara mikroskopis (Hardy et al., 1959). Tujuan
utama melakukan biopsi adalah untuk menegakkan diagnosis, untuk mengevaluasi
perjalanan penyakit, dan mengonfirmasi data klinis dengan keadaan histopatologi
organ. Tindakan biopsi akan menimbulkan luka. Luka dari tindakan biopsi jika
tidak ditangani dengan baik akan menyebabkan beberapa dampak seperti infeksi
kronis maupun perasaan tidak nyaman. Metode biopsi dapat dilakukan pada semua
jaringan tubuh, termasuk pankreas.
Pankreas merupakan suatu organ yang terdiri dari jaringan eksokrin dan
endokrin. Pankreas adalah organ pipih yang terletak di belakang dan sedikit di
bawah lambung dalam abdomen (Sloane, 2003). Pankreas terdiri dari tiga bagian
yaitu kepala, badan, dan ekor. Penyakit yang sering terjadi pada pankreas yaitu
pankreatitis dan kanker pankreas.
Biopsi pada pankreas dilakukan apabila dicurigai adanya gangguan atau
penyakit pada pankreas. Tindakan biopsi pada pankreas memerlukan keterampilan
khusus. Terdapat beberapa metode dengan pengaplikasian yang berbeda sehingga
penting untuk diketahui.
1.2. Rumusan Masalah
Berdasarkan latar belakang, adapun rumusan masalah yang akan dibahas sebagai
berikut:
- Apa yang dimaksud dengan biopsi pada pankreas?
- Apa kegunaan melakukan biopsi pada pankreas?
- Apa saja teknik biopsi pada pankreas?
- Bagaimana teknik biopsi pada pankreas?

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BAB 2
TUJUAN DAN MANFAAT

2.1. Tujuan
Adapun tujuan yang akan dibahas sebagai berikut:
- Mengetahui yang dimaksud dengan biopsi pada pankreas
- Mengetahui kegunaan melakukan biopsi pada pankreas
- Mengetahui macam teknik-teknik biopsi pada pankreas
- Mengetahui prosedur biopsi pada pankreas
2.2. Manfaat
Berdasarkan tujuan, maka manfaat yang diperoleh adalah menambahkan
pengetahui sebagai mahasisma mengenai prosedur biopsi pada pankreas dan
pemahaman tentang kegunaan biopsi pada pankreas serta macam-macam teknik
biopsi pada pankreas.

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BAB 3
TINJAUAN PUSTAKA

3.1. Pankreas
Pankreas merupakan suatu organ yang terdiri dari jaringan eksokrin dan
endokrin. Bagian eksokrin mengeluarkan larutan encer alkalis serta enzim
pencernaan melalui duktus pankreatikus ke dalam lumen saluran cerna. Di antara
sel-sel eksokrin di seluruh pankreas tersebar pulau sel endokrin yang dikenal
dengan pulau-pulau langerhans (Sherwood, 2009). Pulau-pulau langerhans
merupakan mikroorgan endokrin multihormonal di pankreas. Pulau-pulau ini
tampak sebagai kelompok bangunan bulat dengan sel-sel terpendam di dalam
jaringan eksokrin pankreas (Mescher, 2010). Pulau Langerhans tidak dapat dilihat
dengan mata telanjang.
Pulau-pulau langerhans tersusun atas beberapa jenis sel yang berbeda yang
menghasilkan hormone-hormon yang berbeda yaitu sel alfa (α), sel beta (β), sel
delta (δ), dan sel polipeptida pankreas (PP) yang memproduksi glucagon, insulin,
somatostatin dan polipeptida pankreatik secara berturut-turut. Sel sel tersebut
saling berhbungan untuk mempengaruhi melalui efek parakrin dalam pulau-pulau
langerhans. Hal tersebut menunjukan interaksi antar sel yang penting untuk
mempertahankan fungsi normal (Hauge-Evans et al., 2009).
3.2. Biopsi
Biopsi merupakan suatu tindakan diagnostik yang dilakukan dengan
mengambil sampel jaringan atau sel untuk dianalisis di laboratorium, baik untuk
mendiagnosis suatu penyakit atau untuk mengetahui jenis pengobatan atau terapi
yang terbaik bagi pasien. Biopsi juga terkenal dengan pengambilan sampel
jaringan. Biopsi sangat sering dikaitkan dengan kanker. Kanker dapat dideteksi
didalam sel dan jaringan tubuh, dimana sel dapat menjadi tumor atau massa yang
melekat pada organ tubuh. Tergantung dari jenis biopsi yang dilakukan, tindakan
ini dapat dilakukan untuk mengetahui tingkat invasi dari penyakit. Tindakan ini

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juga dapat dilakukan untuk mengeliminasi keberadaan kanker dan untuk

mengetahui apakah tumor bersifat jinak.
Saat melakukan tindakan biopsi sering menggunakan jarum dimana
ketebalan dan panjang jarum tergantung pada bagian tubuh yang akan diambil
sampel jaringannya. Selain menggunakan jarum, biopsi juga dapat dilakukan
dengan probe atau scope yang dapat digunakan untuk memandu dokter dalam
pengambilan sampel. Dalam proses pembedahan biopsi dapat dibagi menjadi dua
yaitu biopsi terbuka dan biopsi tertutup. Jika biopsi dilakukan selama operasi maka
tindakan ini disebut biopsi terbuka dan jika biopsi membutuhkan sayatan kecil
maka itu disebut biopsi tertutup.
Resiko yang dapat terjadi setelah dilakukannya biopsi yaitu terjadinya
infeksi dan pendarahan. Biopsi biasanya akan menyebabkan sedikit pendarahan,
terutama saat biopsi membutuhkan sayatan. Namun setelah sayatan dijahit
pendarahan juga akan langsung berhenti. Pendarahan yang lebih serius terjadi jika
alat yang digunakan untuk mengambil sampel melukai atau merusak pembuluh
darah.
3.3. Biopsi pada Pankreas
Pembedahan pankreas pada anjing dan kucing dapat dilakukan untuk tujuan
terapeutik dan diagnostik. Biopsi pankreas dapat dilakukan pada keadaan hewan
tersebut mengalami pankreatitis akut dan kronis serta neoplasma. Pankreatitis
sangat sulit didiagnosa dengan ante mortem karena tidak ada tes diagnostic yang
memiliki sensitivitas dan spesifisitas sempurna, akan tetapi pemeriksaan histologi
telah disarankan sebagai gold standart untuk diagnose anjing (Watson, 2004) dan
kucing (DeCock et al., 2007).
Biopsi pankreas dapat dilakukan melalui pembedahan yaitu dengan
laparoskopi atau laparotomi (Schlines, 2007). Biopsi pankreas dengan
menggunakan teknik laparotomi dapat menimbulkan potensi komplikasi seperti
peradangan sampai pendarahan. Maka dari itu biopsi pankreas biasanya dilakukan
pada anjing yang digunakan untuk praktik (Ishida et al., 1981; VanEnkevort et al.,
1999). Karena menimbulkan dampak akibat dari laparotomi maka teknik ini
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biasanya dilakukan untuk evaluasi pankreas yang memungkinkan terjadinya

perubahan terkait penyakit pada pankreas.
3.4. Kegunaan Biopsi pada Pankreas
Biopsi pankreas dapat menfasilitasi diagnosis gangguan patologi anatomi
pada pankreas dan kelainan secara primer maupun sekunder seperti pankreatitis
akut dan pankreatitis kronis, insufisiensi eksokrin pankreas (EPI), neoplasia
pankreas, kista pada pankreas, dan hiperplasia nodular jinak. Pankreatitis sangat
sulit didiagnosa secara ante-mortem dengan akurat karena tidak ada tes diagnostik
yang memiliki sensitivitas 100%, meskipun pemeriksaan histologi pankreas telah
disarankan sebagai gold standard untuk diagnosis pankreatitis pada anjing.
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BAB 4
PEMBAHASAN

4.1. Preoperasi Biopsi pada Pankreas

Adapun hal-hal yang perlu dipersiapkan sebelum melakukan biopsi pada
pankreas meliputi persiapan alat, bahan, dan obat, kemudian persiapan ruang
operasi, persiapan pasien (hewan) dan persiapan operator.
- Persiapan alat, bahan, dan obat
Alat-alat atau instrumen bedah yang diperlukan dalam biopsi pada pankreas
harus di sterilisasi. Pada masing-masing metode atau teknik operasi alat-alat
bedah yang diperlukan berbeda yaitu sebagai berikut:
1. videolaparoscopy (A)
2. camera (B)
3. insufflation tubing (C)
4. lampu cable (D)
5. 25-mm trocars and cannulas (E)
6. 5-mm laparoscopic clamshell biopsy forceps (F)
7. 5-mm laparoscope 0° (G)
8. 5-mm laparoscopic blunt probe (H)

Gambar 4.1. Instrumen bedah untuk biopsi pada pankreas

(Sumber: Case dan Alexander, 2015)

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- Persiapan ruang operasi

Tempat operasi harus dalam keadaan bersih dan steril, letakkan alas plastik di
atas meja operasi dan suhu ruangan operasi harus stabil.
- Persiapan pasien (hewan)
Pemeriksaan secara menyeluruh yang meliputi pulsus, frekuensi nafas,
temperatur, dan pemeriksaan seluruh sistema. Selain pemeriksaan fisik juga
dilakukan pemeriksaan laboratorium. Pada kasus-kasus yamg memerlukan
konfirmasi rontgen bisa dilakukan rotngen. Pelaksanaan operasi dilakukan jika
hewan stabil tetapi jika hewan tidak stabil maka distabilkan terlebih
dahuluHewan dengan kondisi menderita diabetes harus dievaluasi dengan
cermat sebelum operasi, termasuk hitung darah lengkap (CBC), panel biokimia
serum (termasuk glukosa darah puasa, nitrogen urea darah, dan kreatinin),
urinalisis, dan kultur urin. Konsentrasi glukosa darah idealnya harus
dipertahankan antara 100 dan 300 mg / dl selama operasi. Hewan dengan
diabetes harus diberi makan sehari sebelum operasi, dan pemberian insulin
harus diberikan. Hewan tersebut harus dipuasakan 6 hingga 8 jam sebelum
operasi dan operasi harus dilakukan di pagi hari. Konsentrasi glukosa darah
harus diukur pagi hari saat operasi. Satu hingga dua jam sebelum operasi, jika
konsentrasi glukosa darah antara 150 dan 300 mg/ dl, maka hewan tersebut
harus diberikan setengah dari dosis pagi hari insulin secara subkutan. Glukosa
darah harus diperiksa pada saat induksi dan setiap jam sesudahnya. Jika kadar
glukosa darah rendah, 0,45% garam dan 2,5% dextrose (10 hingga 15 ml / kg
untuk jam pertama, kemudian 5 ml / kg setelahnya jika darah dan kehilangan
cairan evaporatif kecil) harus diberikan. Jika kadar glukosa darah normal,
berikan larutan Ringer laktat (pada tingkat yang sama). Cairan harus diubah
menjadi 5% dextrose dan tambahan dosis kecil insulin reguler diberikan jika
konsentrasi glukosa darah lebih besar dari 300 mg / dl. Kunci untuk manajemen
pasien diabetes adalah seringnya pemeriksaan glukosa darah dan apresiasi
variabilitas tanggapan pasien terhadap terapi insulin. Hewan diberikan
premedikasi dengan atropine (0.02– 0.04 mg/kg IV) dan jika di butuhkan
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dengan tambahan acepromazine (0.01–0.05 mg/kg IV). Dan anestesi dapat di

induksi dengan thiopental (15 mg/kg) yang dibantu dengan pemberian oxygen
dan dengan isoflurane 1.2–1.7%
- Persiapan operator
Sebelum melakukan operasi, operator maupun co-operator terlebih dahulu
melepas aksesoris yang dapat mengganggu jalannya operasi. Tangan operator
dan cooperator harus steril dalam melakukan operasi untuk menghindari
timbulnya infeksi bawaan dari luar tubuh hewan. Tangan dicuci menggunakan
air bersih dan sabun. Selanjutnya di sterilisasi menggunakan alkohol 70%.
Operator dan co-operator juga harus memperhatikan penghitungan dosis obat
yang diberikan untuk tujuan premedikasi dan anastesi sehingga dosis
pemberian tepat dan pengunaan alat-alat sterilisasi individu digunakan dengan
benar serta menjalankan operasi sesuai SOP.
4.2. Prosedur Biopsi pada Pankreas
Biopsi merupakan prosedur pengangkatan sampel jaringan dari pankreas
(menggunakan jarum atau melalui operasi) untuk diagnosis atau terapi. Menurut
Pratschke et al. (2015), terdapat beberapa teknik bedah untuk biopsi pankreas pada
anjing dan kucing seperti suture fraktur dan teknik diseksi atau ligasi tumpul
dengan menggunakan target lesi secara anatomi dipilih acak atau rando pada site
biopsi. Biopsi Clamshell menggunakan forceps biopsi cup telah dilaporkan pada
anjing dewasa (Cordner et al., 2010). Biopsi pankreas sebagai teknik yang efektif
untuk mengetahui gangguan pada pankreas dikarenakan penyakit pankreas yang
bersifat difus sehingga diperlukan diagnosis yang akurat. Semua prosedur biopsi
dilakukan anestesi lokal dengan lidokain 2% pada beberapa kasus. Penggunaan alat
jarum 16-20G digunakan dengan sistem koaksial dan senapan biopsi otomatis
untuk mendapatkan spesimen biopsi tergantung dari jara antara lesi dan kulit (Tyng
et al., 2015).
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Biopsi umumnya dilakukan dengan teknik sebagai berikut:

1. Brush Biopsy
Prosedur ini dikenal dengan tes Endoscopic Retrograde
Cholangiopancreatography (ERCP). Menggunakan tabung panjang dan tipis
disebut endoskop dimasukkan ke usus kecil, ditempatkan brush kecil pada alat
kemudian masuk ke saluran pankreas dan empedu untuk mengambil sampel
pada sel pankreas dan kantung empedu (King, 2019).
2. Fine Needle Aspiration (FNA) biopsy dan Endoscopic Ultrasound (EUS)
Digunakan CT Scan atau Endoscopic Ultrasound (EUS) untuk
menemukan lokasi tumor atau kanker, kemudian dimasukkan jarum panjang
dan tipis melalui kulit ke dalam tumor lalu sel diangkat melalui jarum (King,
2019). EUS merupakan metode yang lebih sering digunakkan untuk evaluasi
massa pankreas dikarenakan ketepatan diagnostik dan akuisisi jaringan yang
lebih berkualitas (Cordner et al., 2015). Kelebihan metode ini yakni aman, non-
invasive, sensitivitas tinggi, mampu mendeteksi lesi kecil, dan mampu
mengambil sampel histologi. Sedangkan keterbatasan metode ini yaitu jarang
tersedia di beberapa negara dan tidak dapat mendeteksi sel yang metastasis.
EUS merupakan prosedur yang aman, dapat ditoleransi dengan baik, dan
memiliki manfaat tambahan seperti memungkinkan aspirasi jarum halus (FNA)
dilakukan untuk mendapatkan diagnosis sitopatologis dengan jarum 19-Gauge
(Zhang et al., 2018). Metode EUS-FNA bermanfaat bagi diagnosa untuk
mendapatkan jaringan biopsi, dengan sensitivitas yang dikumpulkan lebih dari
85% hingga 92% dan spesifisitas yang dikumpulkan dari 94% hingga 100%
dalam diagnosis lesi pankreas (Chen et al., 2012).

Gambar 4.2. Ringkasan skematis dari teknik Fine Needle Aspriration (FNA)
(Sumber: Huang et al., 2017)
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EUS dilakukan dengan anestesi dan melibatkan pemeriksaan endoskopi

gastrointestinal (GTI) bagian atas dengan echoendoscope. Transduser
echoendoscope diposisikan di dalam lambung, berdekatan langsung dengan
pankreas sehingga memungkinkan perincian gambar resolusi tinggi dari
pankreas dan pembuluh di sekitarnya, kelenjar getah bening dan lobus kiri hati.
Metode ini ideal digunakkan pada lesi kurang dari 2 cm dengan diagnosa
sementara kanker pankreas (Zhang et al., 2018).

Gambar. 4.3. Gambaran Endoscopic Ultrasound (EUS) pada pankreas adanya 3.1 cm
pancreatic adenocarcinoma pada ujung pankreas
(Sumber: Zhang et al., 2018)
3. Laparoskopi
Dengan cara membuat insisi pada abdomen untuk memasukkan tabung
tipis dengan cahaya dan kamera diujungnya, sehingga memungkinkan melihat
keadaan pankreas dan mengambil jaringan melalui insisi kecil lainnya (King,
2019). Metode ini memberikan pandangan yang luas dan terang dari sisi dextra
pankreas, sedangkan sisi sinistra sulit untuk dievaluasi dikarenakan perlunya
diseksi bursa omental dan reposisi pasien (Case dan Alexander, 2015).
Pasien diposisikan secara dorsal recumbency dengan posisi kaki lebih
rendah dari kepala sekitar 15 derajat.

Gambar. 4.4. Posisi pasien dorsal recumbency

(Sumber: Case dan Alexander, 2015)
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Dibuat insisi dari kaudal sampai ke umbilikalis, yang lebarnya tidak

lebih dari diameter kanula, kemudian insisi dilanjutkan hingga linea alba.
Masukkan trokar atau jarum veress atau kateter ke dalam sayatan dengan
kemiringan 30o serta minimalkan resiko tusukan limpa. Setelah kateter masuk,
siram 3 ml saline steril untuk memastikan tidak ada resistensi atau malposisi
kateter. Setelah pneumoperitoneum, lepaskan kateter (atau jarum Veress) dan
masukkan trocar-cannula tumpul atau sekrup berulir di cannula melalui insisi.
Masukkan laparoskop ke dalam kanula dan amati peritoneum untuk
memastikan tidak ada trauma iatrogenik atau perdarahan.

Gambar. 4.5. Prosedur pemasukan trokar atau kateter melalui insisi di abdomen
(Sumber: Case dan Alexander, 2015)

Evaluasi rongga peritoneum dengan memutar laparoskop searah jarum

jam. Masukkan probe tumpul di bawah visualisasi laparoskopi. Laparoskop
digunakan untuk memvisualisasikan dan mengarahkan probe ke abdomen
bagian kranial. Lakukan pemeriksaan hati dan katung empedu untuk melihat
perubahan sekunder dari penyakit pankreas. Probe tumpul dapat digunakan
untuk memanipulasi duodenum, omentum, lambung, atau limpa sesuai
kebutuhan untuk meningkatkan visualisasi bagian dextra pankreas.
Pengambilan sampel dapat dilakukan pada sisi kanan pankreas. Setelah
menemukan lokasi avaskular untuk biopsi, masukkan clamshell biopsi forceps
pada probe tumpul, kemudian pertahankan selama 60-90 detik. Rotasi lembut
forceps akan membantu melepaskan sampel biopsi dari parenkim.
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Gambar. 4.5. Penggunaan probe untuk meretraksi duodenum agar pankreas lebih terlihat.
(Sumber: Case dan Alexander, 2015)

Gambar. 4.5. Penggunaan Clamshell biopsi forceps digunakan untuk mengambil sampel.
(Sumber: Case dan Alexander, 2015)

4.3. Perawatan Setelah Biopsi pada Pankreas

Adapun perawatan pasca operasi biopsi pankreas yang dapat dilakukan yaitu
sebagai berikut.
1. Terapi cairan intravena hewan diberikan premedikasi dengan atropine (0.02– 0.04
mg/kg IV) dan jika di butuhkan dengan tambahan acepromazine (0.01–0.05 mg/kg
IV). Dan anestesi dapat di induksi dengan thiopental (15 mg/kg) yang dibantu
dengan pemberian oxygen dan dengan isoflurane 1.2–1.7% Terapi ini adalah
prioritas yang paling penting pada hewan dengan tingkat dehidrasi yang parah, di
mana pemeliharaan perfusi jaringan dan pankreas sangat penting. Cairan yang
paling umum digunakan adalah larutan Ringer laktat dan larutan garam 0,9%.
Cairan infus berfungsi untuk meningkatkan perfusi organ, dan memperbaiki
ketidakseimbangan elektrolit tubuh. Hipokalemia sering terjadi akibat kehilangan
potasium dari kombinasi diare, muntah, terapi fluida, dan kekurangan makanan
 13

atau anoreksia. Oleh karena itu, potasium serum harus selalu diukur, dan kalium
harus ditambahkan ke cairan intravena bila diperlukan
2. Obat nyeri yang disediakan, biasanya opioid seperti butorfanol, buprenorfin,
oxymorphone, meperidine, mengingat bahwa ini dapat menghambat motilitas
gastrointestinal yang normal
3. Jika muntah atau mual terjadi, maka antiemetik (miropitant, odansetron,
dolasetron, metoclopramide, butorfanol sebagai infus kronis) Hewan biasanya
tidak diberi makanan atau air selama 24-48 jam (atau kadang kadang lebih lama),
untuk memberikan saluran pencernaan dan pankreas waktu untuk proses
penyembuhan; Namun pemberian pakan dianjurkan jika hewan tidak
muntah dan tidak terasa kesakitan.
4. Pemberian air kemudian pemberian makanan harus dimulai dengan sejumlah kecil
makanan rendah lemak (mungkin kurang dari 2 hingga 3 gram lemak / 100 kkal),
makanan lunak (misalnya, nasi, ayam putih yang dihilangkan lemaknya atau kalkun
putih tanpa kulit) dan makanan yang mudah dicerna (karbohidrat sederhana)
makanan yang ditawarkan selama beberapa hari, sampai hewan tersebut dianggap
"normal" di mana saat itu diet normal secara bertahap diperkenalkan kembali.
 14

BAB 5
KESIMPULAN DAN SARAN

5.1. Kesimpulan
Biopsi merupakan suatu tindakan diagnostik yang dilakukan dengan
mengambil sampel jaringan atau sel untuk dianalisis di laboratorium, baik untuk
mendiagnosis suatu penyakit atau untuk mengetahui jenis pengobatan atau terapi
yang terbaik bagi pasien. Biopsi pankreas dapat dilakukan pada keadaan hewan
tersebut mengalami pankreatitis akut dan kronis serta neoplasma. Ada beberapa hal
yang perlu diperhatikan dalam biopsi pada pankreas, diantaranya preoperasi,
prosedur operasi, dan perawatan setalah operasi. Biopsi pada pankreas memiliki
beberapa metode yaitu brush biopsy, Fine Needle Aspiration (FNA) biopsy dan
Endoscopic Ultrasound (EUS), serta laparoskopi. Biopsi pada pankreas dapat
menfasilitasi diagnosis gangguan patologi anatomi pada pankreas.
5.2. Saran
Metode-metode untuk biopsi pada pankreas sangat perlu diperhatikan
karena metode-metode tersebut memiliki tingkat kesulitan yang tinggi dan sangat
beresiko.

14
 15

DAFTAR PUSTAKA
Chen J, Yang R, Lu Y, Xia Y, Zhou H. 2012. Diagnostic accuracy of endoscopic
ultrasound-guided fine-needle aspiration for solid pancreatic lesion: a
systematic review. J Cancer Res Clin Oncol Vol 138: 1433-1441 [PMID:
22752601 DOI: 10.1007/ s00432-012-1268-1]
Cordner, A. P., Sharkey, L.C., Armstrong, P.J., McAteer, K. 2015. Cytologic findings
and diagnostic yield in 92 dogs undergoing fine-needle aspiration of the
pancreas. Journal of Veterinary Diagnostic Investigation Vol. 27(2): 236-240.
Cordner, A. P., Armstrong, J., Newman, S. J. 2010. Effect of Pancreatic Tissue
Handling on Serum Pancreatic Enzyme Levels in Clinically Healthy Dogs.
Journal of Veterinary Diagnostic Investigations Vol 22: 702-707.
De Cock H.E.V., Forman M.A., Farver T.B dan Marks S.L. 2007. Prevalence and
Histopathologic Characteristics of Pancreatitis in Cats. Journal Veterinary
Pathology 44, 39-49.
Hardy JD., Griffin JR., Rodyeuz JA., 1959. Biopsy Manual. London: WD Saunders
Company.
Hauge-Evans.A,King.A,Carmignac.D,Richardson.C, and Robinson.C.L.M, 2009 ,
Somatostatin secreted by islet δ- cells fulfills multiple roles as a paracrine
regulator of islet function.
Huang Y., Shi J., Chen YY., Li K. 2018. Ultrasound-Guided Percutaneous Core Needle
Biopsy for The Diagnosis of Pancreatic Disease. Ultrasound in Med. & Biol.,
Vol. 44, No. 6, pp. 1145–1154.
Ishida H, Furukawa Y, Kuroda H, Kobayashi M, Tsuneoka K. 1981. Laparoscopic
observations and biopsy of the pancrease. Endoscopy 13, 68-73.
King, M. 2017. Biopsy of the Pancreas: Standford health Care. Dapat diaskes:
https://stanfordhealthcare.org/medical-conditions/cancer/pancreatic-
cancer/pancreatic-cancer-diagnosis/biopsy.html. [30 September 2019].
Mescher A.L, 2010. Junqueira’s Basic Histology Text & Atlas (Twelfth Edition). New
York: McGraw-Hill.
Pratschke, K. M., Ryan, J., McAlindent, A., dan McLauchlan G. 2015. Pancreatic
surgical biopsy in 24 dogs and 19 cats: postoperative complications and clinical
relevance of histological findings. Journal of Small Animal Practice Vol 56:
60-66.
Sherwood, L., 2009. Fisiologi Manusia dari Sel ke Sistem. Edisi VI. Jakarta: EGC.
Sloane E. 2003. Anatomi dan Fisiologi untuk Pemula. Jakarta: EGC
Tyng, C. J., Almeida M.F., Barbosa, P., Bitencourt A.G.V., Berg J., Macielll, M.S.,
Coimbra, F., Schiavon, L. H., Begnami, Guimaraes. 2015. Computed
tomography-guided percutaneous core needle biopsy in pancreatic tumor
diagnosis. World Journal Gastroenterology Vol 28; 21(12): 3579-3586.
VanEnkevort BA, O’Brien RT, Young KM. 1999. Pancreatic pseudocysts in 4
dogs and 2 cats: ultrasonographic and clinicopathologic findings. J Vet
Intern Med, 13, 09-313.
Watson P. 2004. Pancreatitis in the Dog: Dealing with a Spectrum of Disease. In
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Birmingham, United Kingdom, p. 13- 15.
Zhang, L., Sanagapalli, S., Stoita, A. 2018. Challenges in diagnosis of pancreatic
cancer. World Journal Gastroenterology Vol 21; 24(19): 2047-2060.
 Submit a Manuscript: http://www.f6publishing.com
DOI: 10.3748/wjg.v24.i19.2047
Challenges in diagnosis of pancreatic cancer
Lulu Zhang, Santosh Sanagapalli, Alina Stoita
Lulu Zhang, Santosh Sanagapalli, Alina Stoita, Department
of Gastroenterology, St. Vincent’s Hospital Sydney, Darlinghurst
2010, NSW, Australia
ORCID number: Lulu Zhang (0000-0003-2040-6158);
Santosh Sanagapalli (0000-0003-3145-1059); Alina Stoita
(0000-0001-9460-2149).
Author contributions: Zhang L made substantial contribution
to the collection and analysis of the data and drafted the initial
manuscript; Sanagapalli S and Stoita A made substantial
contributions to the analysis and interpretation of the data and
Stoita A edited, made substantial contribution in writing and
revised the final manuscript; all authors have given their final
approval of the version published.
Conflict-of-interest statement: Authors declare no conflict of
interests for this article.
Open-Access: This article is an open-access article which was
selected by an in-house editor and fully peer-reviewed by external
reviewers. It is distributed in accordance with the Creative
Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this
work non-commercially, and license their derivative works on
different terms, provided the original work is properly cited and
the use is non-commercial. See: http://creativecommons.org/
licenses/by-nc/4.0/
Manuscript source: Invited manuscript
Correspondence to: Alina Stoita, MBBS, FRACP, Doctor,
Department of Gastroenterology St Vincent’s Hospital Sydney
390 Victoria Street, Darlinghurst 2010, NSW,
Australia. astoita@stvincents.com.au
Telephone: +61-283826622
Fax: +61-83826602
Received: March 28, 2018
Peer-review started: March 30, 2018
First decision: April 11, 2018
Revised: April 28, 2018
Accepted: May 11, 2018
Article in press: May 11, 2018
Published online: May 21, 2018
WJG|www.wjgnet.com
World J Gastroenterol 2018 May 21; 24(19): 2047-2060
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
REVIEW
Abstract
Pancreatic cancer is a growing source of cancer related
death, yet has poor survival rates which have not improved
in the last few decades. Its high mortality rate is attributed
to pancreatic cancer biology, difficulty in early diagnosis
and the lack of standardised international guidelines
in assessing suspicious pancreatic masses. This review
aims to provide an update in the current state of play in
pancreatic cancer diagnosis and to evaluate the benefits
and limitations of available diagnostic technology. The
main modalities discussed are imaging with computed
tomography, magnetic resonance imaging, endoscopic
ultrasound and positron emission tomography and tissue
acquisition with fine needle aspiration. We also review the
improvements in the techniques used for tissue acquisition
and the opportunity for personalised cancer medicine.
Screening of high risk individuals, promising biomarkers
and common mimickers of pancreatic cancer are also
explored, as well as suggestions for future research
directions to allow for earlier detection of pancreatic
cancer. Timely and accurate diagnosis of pancreatic cancer
can lead to improvements in the current poor outcome of
this disease.
Key words: Pancreatic cancer; Diagnosis; Challenges;
Imaging; Biomarkers; Screening; Endoscopic ultrasound;
Pitfalls
© The Author(s) 2018. Published by Baishideng Publishing
Group Inc. All rights reserved.
Core tip: Pancreatic cancer is becoming a leading cause
of cancer related death in Western societies. Rapid and
accurate diagnosis of a pancreatic mass is crucial for
improving outcomes. Current practice utilises multi-
detector computed tomography and/or magnetic reson­
ance imaging, with a dedicated pancreas protocol as the
initial modality. endoscopic ultrasound is the preferred
method to further evaluate pancreatic masses as it has
more superior diagnostic accuracy and can provide
tissue acquisition. Pitfalls in diagnosis of pancreatic
2047 May 21, 2018|Volume 24|Issue 19|
 Zhang L et al . An update of current diagnostic modalities
cancer are discussed, as careful recognition of these
conditions is important. There are exciting developments
of new diagnostic techniques that open the possibility of
personalised cancer medicine.
Zhang L, Sanagapalli S, Stoita A. Challenges in diagnosis of
pancreatic cancer. World J Gastroenterol 2018; 24(19): 2047-2060
Available from: URL: http://www.wjgnet.com/1007-9327/full/
v24/i19/2047.htm DOI: http://dx.doi.org/10.3748/wjg.v24.
i19.2047
INTRODUCTION
Pancreatic cancer is the fourth leading cause of cancer
related death in Western societies and is projected to
be the second leading cause within a decade. It has
an average annual incidence rate of 12.5 per 100000
population (which is 3% of all cancers) in America, but
has a disproportionately high mortality, with an average
[1]
annual death rate of 10.9 per 100000 . Pancreatic
cancer is difficult to be diagnosed at an early stage,
with the vast majority of cancers found to be already
metastatic at the time of initial diagnosis. Only 9.7%
of pancreatic cancer are at a local stage at time of
[2]
diagnosis . These poor survival rates have not changed
significantly in nearly 40 years.
Ductal adenocarcinoma and its variants account for
over 90% of pancreatic malignancies. Presenting features
of this disease may include weight loss, jaundice,
malabsorption, pain, dyspepsia and nausea; however,
many patients are asymptomatic and no early warning
signs of pancreatic cancer have been established.
Known risk factors for pancreatic cancer include
[3]
cigarette smoking (relative risk increase of 2.5 times ),
[4]
high body mass index and lack of physical activity ,
[5] [6]
diabetes and chronic pancreatitis . Furthermore, there
are also a number of inherited cancer syndromes linked
to pancreatic cancer including Hereditary Breast and
Ovarian Cancer Carriers of the BRCA1 or BRCA2 germline
mutations, familial atypical multiple mole melanoma syn­
drome (FAMMM), Peutz-Jeghers syndrome, hereditary
pancreatitis, Hereditary Nonpolyposis Colorectal Cancer
(Lynch Syndrome) and familial pancreatic cancer. These
higher risk groups may be a good target for screening
and early diagnosis programs.
Surgical resection is the only curative treatment
for pancreatic cancer. Unfortunately, because of late
presentation, only 15% to 20% of patients are candi­
dates for pancreatectomy. Furthermore, prognosis is
poor, even after a complete resection. Five year survival
after pancreaticoduodenectomy, or Whipples procedure,
is approximately 21% for negative margin resections
(R0) and 11% for microscopically positive margin
[7]
resections (R1) . Even in patients with negative margin
resections with presumed curative intent, up to 71% can
[7]
have disease recurrence .
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The motivation for this research is the dismal out­
comes for pancreatic cancer that have failed to signi­
ficantly improve; it is this that is the key problem to
be solved. The main focus of this review is to describe
the current state of play in pancreatic cancer diagnosis.
Rapid and accurate diagnosis of a pancreatic mass is
crucial for improving outcomes. After evaluating the
evidence underpinning all of the widely used modalities
for diagnosis, we intend to make a comparison of these
modalities and provide an evidence-based algorithm for
diagnosis.
The main objective of this review was to evaluate
and compare the suitability and accuracy of the current
diagnostic modalities that exist for pancreatic cancer. We
are currently lacking effective diagnostic and screening
modalities to diagnose pancreatic cancer at an early,
and therefore more likely curative stage. Therefore, it
is valuable to have a thorough understanding of the
currently available diagnostic technology, including its
benefits and limitations, in order to provide direction
for future research. Pitfalls and mimickers of pancreatic
cancers, biomarkers and the current screening programs
in high risks individuals will also be discussed.
LITERATURE SEARCH
A Medline search was conducted using the following
keywords and phrases: “pancreatic cancer, diagnosis,
imaging, biomarkers, screening, endoscopic ultrasound,
pitfalls”, with a focus on more recently published re­
search. In addition, we performed a manual review of
the reference lists of the primary and review articles to
ensure identification of all relevant articles. In particular,
large scaled meta-analyses and systematic reviews were
preferred.
RESULTS
Diagnosis relies on imaging modalities such as computed
tomography (CT), magnetic resonance imaging (MRI),
positron emission tomography (PET) and endoscopic
ultrasound (EUS) that are used along with tissue ac­
quisition. Early detection is the only way of identifying
small cancers and proceeding with curative surgery. We
describe the different diagnostic modalities that currently
exist, evidence underpinning their use and compare
the benefits and disadvantages of each. Table 1 below
provides a summary of our findings and figure 1 shows
a suggested algorithm based on our findings for the
evaluation of a patient with pancreatic cancer.
CT SCANNING
Multi-detector computed tomography (MDCT) is the
most widely available and best-validated tool for imaging
patients with pancreatic adenocarcinoma. MDCT takes
reproducible multi-planar imaging which provides good
spatial resolution and attenuation between tumour and
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 Zhang L et al . An update of current diagnostic modalities

Table 1 Benefits and limitations of pancreatic cancer diagnostic modalities

Diagnostic modalities Advantages Limitations

MDCT Most commonly available Nephrotoxicity
Best validated Radiation exposure
Cheapest
MRI Superior imaging Expensive
Depiction of local pancreatic disease Less available
Iodine-free and no radiation Contraindicated with some metal implants
EUS +/- FNA Safe and less invasive Less available in some countries
High sensitivity Operator dependent
Able to detect small lesions Inability to detect distant metastasis
Able to take histological sample
PET/CT Metastatic disease detection Expensive
Clarification of equivocal CT findings Less available
Monitoring recurrence and response to adjuvant therapy Radiation and contrast exposure

CT: Computed tomography; MDCT: Multi-detector computed tomography; MRI: Magnetic resonance imaging; EUS: Endoscopic ultrasound; FNA: Fine
needle aspiration; PET: Positron emission tomography.

Clinical suspicion of
pancreatic cancer

CT or MRI with
pancreas protocol
1
MDT review

Mass in pancreas No mass in pancreas

on imaging on imaging

No metastatic No metastatic
Metastatic disease Metastatic disease
disease disease

Biopsy confirmation Biopsy confirmation If ongoing clinical

of metastatic site of metastatic site suspicion, consider
EUS + FNA EUS +/- FNA to
confirm absence of
pancreatic cancer

Figure 1 Algorithm for the evaluation of a patient that has clinical suspicion of pancreatic cancer. 1Multi-disciplinary review should involve a panel including
gastroenterologist, surgeon, medical and or radiation oncologist, diagnostic imaging and pathologist. CT: Computed tomography; MDCT: Multi-detector computed
tomography; MRI: Magnetic resonance imaging; EUS: Endoscopic ultrasound; FNA: Fine needle aspiration.

background pancreatic parenchyma with wide anatomic
coverage, and thus allowing comprehensive examination
[8]
of local and distant disease in one single section .
Numerous international guidelines endorse the use
of CT as the initial modality in diagnosis of suspected
[9,10]
pancreatic cancer . In particular, MDCT is best
[10]
performed according to a dedicated pancreas protocol .
Despite some inter-institutional variability, the standard
MDCT pancreas protocol is a helical type scan that
takes interval images of 0.5 to 1 sub-millimetres, with
two phases: pancreatic parenchymal phase at 40 to 50
seconds and portal venous phase at 65 to 70 seconds.
The majority of modern scanners are 128 and 256
slice scanners. It includes the administration of both
intravenous high iodine concentrated contrast, injected
at a rate of 3 to 5 mL per second and ingestion of
neutral oral contrast. The pancreatic phase is described
as the intermediate between the arterial and hepatic
phase where maximal enhancement of the pancreas
is achieved to see the contrast between tumour and
pancreatic parenchyma, as well as visualization of the
[11]
peri-pancreatic arteries and veins . The image is usually
reconstructed in the following ways: (1) axial views at 2
to 5 mm thickness; (2) coronal and sagittal views with
multi-planar reformats at 2 to 3 mm thickness; and (3)
vascular evaluations with maximum intensity projections

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 Zhang L et al . An update of current diagnostic modalities
Figure 2 Axial and coronal plane view on computed tomography of a patient with a 2 cm mass in the body of pancreas (blue arrow), abutting splenic
artery (red arrow).
or three dimensional (3D) volumetric thick sections.
Pancreatic cancer appears on CT as an ill-defined
mass that enhances poorly compared to adjacent normal
pancreatic tissue; thus appearing hypodense on arterial
phase scans in 75% to 90% of cases, but may become
isodense on delayed scans. Findings which may be
predictive of pancreatic cancer include, from lowest to
highest specificity: ductal dilatation (sensitivity 50% and
specificity 78%), hypo-attenuation (sensitivity 75% and
specificity 84%), ductal interruption (sensitivity 45% and
specificity 82%), distal pancreatic atrophy (sensitivity
45% and specificity 96%), pancreatic contour anomalies
(sensitivity 15% and specificity 92%), and common bile
[12]
duct dilation (sensitivity 5% and specificity 92%) .
Figure 2 demonstrates two views on CT imaging of a
pancreatic cancer which has abutted into the splenic
artery.
When compared with other imaging modalities, CT
performs well in the diagnosis of pancreatic cancer. A
large meta-analysis comparing various imaging mo­
dalities for the diagnosis of pancreatic cancer found a
combined sensitivity and specificity of 89% and 90%
[13]
respectively for CT , which was equivalent to MRI.
There has been reported improvement in the detection of
pancreatic cancer with recent suggestions of sensitivities
up to 96% for MDCT, secondary to acquisition of thin
collimation images, improved spatial and temporal reso­
lution and use of multi-planar reconstruction and 3D
[14]
technique .
Multi-planar reconstruction on CT is important in
tumour staging; providing selective visualization of im­
portant arterial and venous structures. This allows for
precise visualization of the relationship of the primary
tumour to the superior mesenteric artery (SMA), superior
mesenteric vein (SMV) and coeliac axis thereby providing
an assessment of vascular invasion and resectability. CT
is able to distinguish abutment, encasement, narrowing,
or occlusion of the portal vein/SMV at the confluence and
allow the surgeon to determine if a venous reconstruction
[14]
is technically feasible . The accuracy of CT in assessment
of vascular invasion is not strong, with the most recent
studies showing a sensitivity of only 60% and specificity
94% when determining involvement of surrounding
WJG|www.wjgnet.com
[15]
vessels . The reason for favouring specificity over
sensitivity for vascular invasion is to avoid denying
[16]
surgery to patients with potentially resectable tumours .
Despite these values, consensus statements suggest that
preoperative evaluation of surgical resectability be based
[17]
on CT . CT is also able to provide 3D reconstruction
which can be very useful for pre-operative planning by
the surgeon.
CT also plays an important role in predicting un­
resectability. If the tumour surrounds a vessel by more
than 180 degrees and occlusion of the SMV/portal
vein without surgical options of reconstruction, then it
[14]
is deemed T4 disease and is unresectable . Recent
studies have demonstrated that CT’s sensitivity for
unresectable disease is between 52% to 91%, and
[18]
specificities of 92% to 100% . One study also showed
that different generations of MDCT equipment did not
[19]
impact these values .
CT also provides the benefit of diagnosing distant
intra-abdominal and/or lung metastasis, which is im­
portant given that diagnosis of pancreatic cancer is
often delayed. Findings of peritoneal carcinomatosis
on CT include ascites, peritoneal thickening, contrast
enhancement, nodular bowel wall thickening, and soft-
[16]
tissue infiltration of the omentum .
Whilst overall a safe, non-invasive and relatively
cheap test to perform, contrast CT is accompanied by the
risk of nephrotoxicity from the iodine-contrast agent and
as well as involving exposure to radiation. There is also
individual variability in getting parenchyma enhancement
due to technical factors such as the generation of CT
scanner, contrast material volume and concentration
and rate of injection, and patient factors such as age,
[8]
weight and cardiac output . Despite this, most centres
still endorse the use of MDCT as the first line modality
of choice for diagnosing pancreatic cancer and should
not be substituted by other more advanced imaging
modalities.
MRI
MRI of the pancreas works by evaluating the speed
of the diffusion process by random translational mole­
2050 May 21, 2018|Volume 24|Issue 19|

A B
D E
Figure 3 Multimodal imaging techniques utilised for a patient with 2.8 cm head of pancreas cancer (blue arrow) with portal vein and superior mesenteric
vein invasion. A: Hypodense mass on coronal view on CT; B: T1-weighted coronal view on MRI; C: T1-weighted axial view on MRI; D: MRCP view with dilated CBD
and PD (double duct sign); E: Axial view on PET CT imaging showing marked FDG avidity. CT: Computed tomography; MDCT: Multi-detector computed tomography;
MRI: Magnetic resonance imaging; PET: Positron emission tomography; MRCP: Magnetic resonance cholangiopancreatography; FDG: Fluorodeoxyglucose.
cular motion which differs between extracellular and
intracellular components of tissue, as well as differences in
[20]
tissue cellularity and cell density . The pancreas protocol
for MRI includes several sequences: T2-weighted single-
shot fast spin-echo (SSFSE), T1-weighted in-phase and
opposed-phase gradient echo (GRE), T2-weighted fat-
suppressed fast spin-echo (FSE), and diffusion-weighted
imaging (DWI) all provide an axial plane with less than
[21]
6mm thick slices . There is also the option to have pre-
and dynamic post- IV contrast administration (gadolinium)
3D T1-weighted fat-suppressed gradient- echo (in
pancreatic, portal venous, and equilibrium phases) which
provides an axial plane but with the thinnest possible
[21]
slices of 2 to 3 mm . Pancreatic adenocarcinomas
normally appear hypo-intense to normal pancreas on
precontrast T1-weighted images and hypointense or
[16]
isointense on post-contrast T1-weighted images , as
seen in Figure 3.
MRI theoretically allows tumour detection at an
earlier stage by providing a comprehensive analysis of
the morphological changes of the pancreas parenchyma,
as well as that of the pancreatic duct. Despite this, in
meta analyses, MRI has only been shown to be equally
sensitive and specific in diagnosing and staging pan­
creatic cancer as CT; with a combined sensitivity and
[13]
specificity of 89% and 89% respectively . This is
likely due to the difficulty in demonstrating a significant
benefit when the sensitivity and specificity of CT are
already relatively high. For this reason, MRI is not widely
used as the primary imaging modality in most centres
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Zhang L et al . An update of current diagnostic modalities
C
[9]
due to issues of its cost and availability . Most experts
nevertheless acknowledge the added utility of MRI over
CT in certain situations; including the main benefit in
differentiating iso-attenuating pancreatic lesions and in
characterization of indeterminate liver lesions identified
[9]
at prior CT examinations . MRI is also valuable in
patients with impaired renal function or patients with
sensitivities to iodinated contrast. Furthermore, other
specific situations MRI seems to have an advantage over
CT is in differentiating pancreatic tumours from mass-
forming pancreatitis, for tumours less than 2 cm, in
the presence of hypertrophied pancreatic head or focal
[22]
fatty infiltration of the parenchyma . In the authors’
experience, MRI is often used as a second-line test when
there is a high clinical suspicion of pancreatic tumour
despite none being visible on CT.
EUS WITH FINE NEEDLE ASPIRATION
EUS is performed under sedation and involves an upper
gastrointestinal endoscopic examination with the use
of an echoendoscope. The echoendoscope transducer
is positioned in the stomach, in direct proximity to the
pancreas so that it enables detailed high-resolution
imagines of the pancreas and surrounding vessels,
lymph nodes and left lobe of the liver. EUS is a safe,
well-tolerated procedure and has the added benefit of
allowing fine needle aspiration to be performed in order
to obtain a cytopathological diagnosis. It is particularly
ideal for lesions less than 2 cm or when there is a clinical
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 Zhang L et al . An update of current diagnostic modalities
A B
Figure 4 Endoscopic ultrasound images of (A) a small pancreatic adenocarcinoma in the head of the pancreas (1.8 cm) not seen on other modalities; and (B)
a 3.1 cm pancreatic adenocarcinoma in the tail of the pancreas.
suspicion of pancreatic cancer but other modalities have
failed to identify a mass and for obtaining a confirmatory
biopsy. Figure 4 demonstrates the appearance of
pancreatic cancers on EUS imagining.
In large meta-analyses EUS with fine needle aspi­
ration (EUS-FNA) was found to be highly accurate in
not only diagnosing malignancy but also in diagnosing
the correct aetiology for solid pancreatic masses, with
[23-26]
sensitivity of over 85% and specificity of 96%
Longitudinal studies have also observed a significant
increase in diagnostic accuracy over time, likely reflecting
an increase in operator proficiency with experience
and better visualisation with newer echoendoscopes.
The increase in the diagnostic accuracy was seen from
1995-2000 to 2001-2010, with pooled sensitivity of
83.0% increasing to 87.8%, while the pooled specificity
[23]
remained high at 96.6% and 95.6% . EUS is also used
as a reliable tool for local staging, as studies have shown
a sensitivity and specificity of 72% and 90% respectively
for T1-2 staging, 90% and 72% respectively for T3-T4
staging, and 87% and 92% respective for vascular
[27]
invasion .
The evidence suggests that EUS may have distinct
advantages in pancreatic cancer diagnosis when com­
pared with other modalities. Comparative studies with
CT have demonstrated the superiority of EUS in primary
tumour detection and staging with the absence of a focal
mass lesion on EUS reliably excluding pancreatic cancer
irrespective of clinical presentation with a negative
[28]
predictive value of 100% . It has also been shown
that the diagnostic accuracy of EUS when no identifiable
[29]
mass was found on spiral CT was 92% . In a recent
meta-analysis, CT scan showed lower sensitivity than
EUS for nodal staging (24% vs 58%) and vascular
invasion (58% vs 86%); however, the specificities for
nodal staging (88% vs 85%) and vascular invasion
(95% vs 93%) were comparable in studies where both
[30]
imaging techniques were performed . EUS has its
greatest benefit over CT and MRI for small pancreatic
neoplasms (less than 2 cm), having a sensitivity of 94%
[31]
compared with 69% for MDCT and 83% for MRI .
Still, perhaps the clearest demonstration of the
benefits of EUS-FNA is its ability to obtain a tissue biopsy.
Large meta-analyses have demonstrated supe­riority
of EUS-FNA, with pooled sensitivity of more than 85%
WJG|www.wjgnet.com
to 92% and pooled specificity of 94% to 100% in the
[23-25,28]
diagnosis of pancreatic lesion . EUS is also shown
to be the best imaging modality for detecting vascular
(especially portal vein) invasion, with a reported accuracy
[29]
of 82%, compared with CT’s accuracy of 79% . The
[32]
overall complication rate of EUS-FNA is very low 0.85%
(including infection, self-limiting pancreatitis) and if the
tumour is in the head of pancreas, the needle tract will
. be part of the resected specimen thus minimising the
risk of tumour seeding. Tumour seeding during EUS-FNA
is a rare but important complication to be considered,
[33,34]
with only a few case reports ever documented . Apart
from this, other major complications such as perforation,
[24]
are extremely rare with a risk of 1:2500 .
Fine needle aspiration technique
Different techniques in retrieving samples have been
investigated for EUS including “fanning”, “slow pull” and
the “wet suction” technique (WEST). Randomised trials
comparing “fanning”, which involves sampling multiple
areas within a lesion with each pass, with standard
technique found that fanning was superior and fewer
[35]
passes were required to establish the diagnosis .
There was however no difference in diagnostic accuracy,
[35]
technical failure or complication rates . As for the “slow
pull” technique, where minimum negative pressure is
provided by removing the stylet from the needle slowly
and continuously, lower scores for contamination with
blood were found, with a higher sensitivity of diagnosis
[36]
of malignancy . Lastly, the WEST technique, which
involves flushing the needle with 5 mL of saline solution
to replace the column of air within the lumen of needle
to improve the quality of aspirate, also resulted in
significantly better cellularity and specimen adequacy
in cell blocks and specimen adequacy, but had no
[37]
difference in the amount of blood contamination .
On-site cytopathologist
The presence of an on-site cytopathologist has a bene­
ficial effect on the diagnostic yield of EUS FNA, by sig­
nificantly lowering the number of inadequate samples,
and increasing the diagnostic sensitivity and overall
[38,39]
accuracy for malignancy . Studies demonstrated the
cost effectiveness of having an on-site cytopathologist
where the same accuracy of 87% was achieved with
2052 May 21, 2018|Volume 24|Issue 19|

only 2.1 passes, compared to the 4 passes needed when
[40]
real-time evaluation of specimens was not available .
Contrast-enhanced EUS
Contrast-enhanced EUS (CE-EUS) is a technique in which
during the EUS, a second-generation low mechanical
index microbubble ultrasound agent (UCA) is injected
peripherally. Due to its small size (2 to 10 µm), it detects
very slow flow and provides real time perfusion imaging
without the burden of Doppler-related artefacts .
[41]
Observational studies have demonstrated more accu­
rate characterization of solid pancreatic lesions seen
on EUS by estimating their vascularity after injecting a
contrast agent. It was also found that a hyper-enhancing
lesion on CE-EUS was highly specific (more than 98%)
for excluding adenocarcinoma, while a hypo-enhancing
and hypo-echoic lesion was highly sensitive (more than
[41]
86%) for adenocarcinoma . It also helps differentiate
between a pancreatic adenocarcinoma (because of
lower uptake of contrast, or hypoenhancement) and
neuroendocrine tumours (NET), lymphoma, metastasis,
and pseudo-papillary tumours that mimic cancer but
show hyper-enhancement on CE-EUS. CE-EUS is bene­
ficial in confirming that small pancreatic lesions are NET
(hypervascular lesions with early arterial enhancement),
characterisation of a mural nodule and malignant
[42]
transformation of intrapapillary mucinous neoplasms
and in providing further information on solid masses in
patients with chronic pancreatitis. There is also potential
to utilise CE-EUS for targeted EUS FNA to improve the
accuracy of biopsy by avoiding necrotic tissue and by
selecting the most adequate target. There are minimal
studies available assessing this and so this poses a
potential topic for future research.
Despite these findings, CE-EUS is not yet widespread
in all centres around the world. CE-EUS should not be
used in patients with unstable angina and there is a
small chance of an allergic reaction to the contrast.
EUS fine needle aspiration versus fine needle biopsy
There has been recent research looking into techniques
to increase the amount of tissue acquisition to improve
the diagnostic accuracy of samples. Fine-needle biopsy
needles (EUS-FNB) have been designed in order to allow
core biopsies with preserved architecture which would
enable histological analysis, by shearing tissue from the
target lesion. Initially, 19-gauge calibre needles were
utilised but the mechanical friction caused by the torqued
echoendoscope limited its use for evaluating pancreatic
[43]
head masses . Studies assessing Trucut needles
showed that there was no significant difference between
the diagnostic accuracy of 19-gauge Trucut needle and
EUS-FNA needle, with a reported accuracy of 78% and
[44]
89% in one study . However, there were more technical
issues experienced with Trucut needle.
Newer 19-gauge, 22-gauge 25-gauge EUS needles
with reverse bevel technology (Pro-core, Cook Medical;
Winston Salem, NC, United States), Franseen type needles
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Zhang L et al . An update of current diagnostic modalities
(Acquire, Boston Scientific, Marlborough, MA, United
States) and fork-tip needles (Shark Core, Medtronic,
Minneapolis, MN, United States) were developed to
overcome the technical issues which allowed acceptable
histological core samples and cytology aspirates, with
[45]
diagnostic accuracies of more than 90% .
A study comparing 22-gauge FNA and FNB needles
showed diagnostic cytologic specimens in 89.3% of
patients and histologic specimens in 80% of patients
[43]
with solid pancreatic mass lesions . Similarly, a recent
meta-analysis showed no significant difference in dia­
gnostic adequacy (75.2% vs 89.0%), or diagnostic
accuracy (85.8% vs 86.2%) between biopsy and
[46]
aspiration needles . Most recently, a small retrospective
study showed better results with a 25-gauge core biopsy
needle reporting a combined cytological and histologic
sensitivities of 85%, specificities of 100% and accuracies
[47]
of 86% with a single pass and minimal complications .
If the FNB needle design can be further improved
and be routinely shown to provide diagnostic yields high
enough to eliminate the need for on-site cytopathological
evaluation, then this could also lead to a significant re­
duction in the costs of pancreatic cancer.
EUS elastography
EUS elastography measures tissue elasticity in real time
using a dedicated software during an EUS examination.
Elasticity is depicted using a colour map, where hard
tissue is shown in dark blue, medium hard tissue in
cyan, tissue with intermediate hardness in green,
medium soft tissue in yellow and soft tissue as red.
Pancreatic malignancy appears as a heterogenous blue
predominant mass, whereas normal pancreas appear
as homogeneous green and inflammatory pancreatic
masses have a heterogeneous, green-predominant
[48]
appearance . The sensitivity and specificity of EUS
elastography to differentiate benign from malignant
pancreatic lesions has been reported as 92.3% and
80.0%, respectively, compared to 92.3% and 68.9%,
[49]
respectively, for the conventional EUS B-mode images .
Elastography is mainly used in Europe. It does have
limitations, as colour pattern provides a subjective
determination and has intra-observer and inter-observer
variability. Other studies reviewing elastography has not
been strong and so more research is required to make
conclusions regarding its benefits.
While elastography and CE-EUS provide additional
benefits to standard EUS, the combination of elas­
tography and CE-EUS does not significantly increase
the diagnostic accuracy of either of the techniques
[50]
performed alone . Each modality has its benefits in
selected cases.
PET
PET with F-18-fluorodeoxyglucose (18FDG) has no
additional benefit in diagnosis of pancreatic cancer.
However, a more recent triple phase enhanced 18FDG-
2053 May 21, 2018|Volume 24|Issue 19|
 Zhang L et al . An update of current diagnostic modalities
PET has been combined with CT to produce one fusion
image, as seen in Figure 3. At this point in time, experts
do not recommend PET/CT as a substitute for high-
quality contrast-enhanced CT because its role is still
[9]
being established . Despite this, the research has
been promising with the use of PET/CT for staging. A
meta-analysis has shown that the pooled sensitivity of
PET in diagnosis, in evaluating N staging and in liver
metastasis were 91%, 64% and 67% respectively; and
the corresponding specificities were 81%, 81% and
[51]
96% respectively . These values are higher than CT
alone. However, as a diagnostic tool, PET/CT performs
similarly to CT alone and hence adds no benefit over the
current primary diagnostic tools in diagnosing pancreatic
[52]
cancer .
Though the value of PET/CT alone for diagnosing
pancreatic cancer has not been shown to be better,
some studies have investigated its combined use with
other techniques. A meta-analysis has shown that the
combination of PET/CT plus endoscopic ultrasonography
is useful for suspected pancreatic cancer because of
the high sensitivity of PET/CT and the high specificity
[53]
of endoscopic ultrasonography . While initially it was
hoped that PET/CT will be able to differentiate between
mass-forming chronic pancreatitis and pancreatic cancer,
this is not the case due to considerable overlap between
the Standardised Uptake Value (SUVmax) values of
[54]
these two diseases . FDG PET/CT has been shown to
provide additional benefit in detecting distant metastasis,
[55]
particularly bone metastasis .
PET/CT shows promising role in assessing tumour
response to chemo-radiation therapy with the measure­
ment of the change in SUV pre- and post- treatment,
which could potentially serve as a trial for preoperative
[56,57]
neoadjuvant therapies .
In conclusion, at the present stage, PET/CT has no
role in routine diagnosis of pancreatic cancer but can be
used as an adjuvant modality in selected cases.
ULTRASOUND AND
ENDOSCOPIC RETROGRADE
CHOLANGIOPANCREATOGRAPHY
The pancreas is a retroperitoneal organ and hence
the sensitivity of transabdominal ultrasound is poor in
detecting pancreatic cancer and is not used in diagnosis
[58]
or staging of pancreatic cancer . The sensitivity ac­
cording to studies vary between 48% and 89% with
lower specificity and accuracy, with variation in these
rates with the size of the tumour and operator’s level of
[59]
experience .
Given the excellent modern imaging, Endoscopic
retrograde cholangiopancreatography (ERCP) plays a less
[60]
prominent role in diagnosis of pancreatic cancer , and
is mainly used as a therapeutic modality due to potential
complications such as pancreatitis and perforation .
[61]
ERCP remains an important modality to provide biliary
drainage in obstructing head of the pancreas cancer
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and can provide biliary and pancreatic duct brushing
[62]
cytology in patients with invasive pan­creatic cancer .
Pancreatogram obtained during the ERCP can show
pancreatic duct stenosis, obstruction, narrowing and
abnormal branching of the main pancreatic duct,
obstruction and encasement of the common bile duct.
There are few studies that looked at ways to attain
cytological samples during ERCP through the use of an
endoscopic naso-pancreatic drainage (ENPD) tube which
is placed in the main pancreatic duct to collect pancreatic
juice repeatedly - a technique known as serial pancreatic-
juice aspiration cytologic examination or “SPACE” .
[63]
Only small-scale studies have examined the use of this
technique with relatively promising results
[63-65]
, but more
research is required prior to recommendation of its use.
BIOMARKERS
At present, there is no reliable diagnostic biomarker
for pancreatic cancer. A number of potential tumour
markers have been evaluated, but the most extensively
studied for diagnosing pancreatic cancer is carbohydrate
antigen 19-9 (CA 19-9). CA 19-9 is however expressed
and shed in a number of pancreatic and hepatobiliary
diseases, as well as other malignancies. CA 19-9 may be
falsely positive in cases of biliary infection, inflammation,
or obstruction (regardless of aetiology) and does not
[66]
necessarily indicate cancer or advanced disease . For
these reasons, it performs poorly as a screening tool,
[66]
with a low positive predictive value of 0.5% to 0.9% .
However, CA 19-9 does have a role as a prognostic
[9]
marker and for monitoring for recurrence after resection .
It performs better in symptomatic patients, with a
sensitivity and specificity of 79% to 81% and 82% to
90% respectively for the diagnosis of pancreatic cancer
[67,68]
in this setting ; with a CA 19-9 serum level of 100 U/mL
[67]
suggestive of unresectability or metastatic disease .
As well as its issues with specificity, CA 19-9 sensitivity
is also suboptimal; for example, CA 19-9 may be
undetectable in Lewis antigen-negative individuals and
hence can be negative in patients with advanced cancer.
There are a number of potential pancreatic cancer
biomarkers that are being investigated. in particular, serum
macrophage inhibitory cytokine 1 (MIC-1) is a promising
biomarker whose levels in the serum are typically elevated
in patients with pancreatic adenocarcinoma. Though
performing sub-optimally when used on its own, it has
been shown to produce improved diagnostic accuracy
[69]
when combined with CA 19-9 . Other studies have also
studied single research biomarkers such as CECAM-1,
Span-1, DUPAN-2, Alpha4GnT, PAM4, and combined
[70,71]
biomarkers with CEA, CA 19-9, and CA 242 , but none
demonstrating sufficient diagnostic accuracy to be used as
a screening test at this stage.
More recently, a combined panel of protein and
microRNAs serum exome for pancreatic cancer have
emerged as potential diagnostic tools with improved
sensitivities and specificities but have yet to have testing
2054 May 21, 2018|Volume 24|Issue 19|

[72]
within larger cohorts . There has also been early
research reviewing the use of inorganic nanomaterials
such as gold and carbon nanotubes which can be tar­
geted towards specific pancreatic cancer cells, in early
[73]
detection and diagnosis .
SCREENING PROGRAMS
Pancreatic cancer screening is not feasible in the general
population due to the low incidence of pancreatic cancer
and lack of a cheap, easy and accurate screening test.
However, approximately 5% to 10% of pancreatic
cancers are due to a known genetic mutation and/or
have familial aggregation. As pancreatic cancer patients
become symptomatic later in the course of the disease,
early detection programs have been developed in
asymptomatic people at high risk of pancreatic cancer
(individuals with a 5% or more lifetime risk of pancreatic
cancer). The high-risk groups include familial pancreatic
cancer (members of a family with at least 2 first
degree relatives with pancreatic cancer) and inherited
pancreatic syndromes including Peutz-Jeghers syndrome
(lifetime risk of pancreatic cancer 36%), familial atypical
multiple mole melanoma syndrome (lifetime risk 17%),
hereditary pancreatitis (lifetime risk 49%), PALB2
mutation, known BRCA2 carrier with a first degree with
pancreatic cancer, Lynch syndrome with a first degree
[74]
with pancreatic cancer . In these high risk groups, the
International Cancer of the Pancreas (CAPS) Consortium
recommends starting screening at age 50, with yearly
surveillance if no pancreatic lesions are detected at
[75]
baseline assessment . EUS and MRI are the imaging
modalities of choice for screening as they have sufficient
sensitivities and specificities to detect small lesions (or
early cancer) and do not carry the risks of radiation
exposure. In these high risk groups, the overall yield for
detecting premalignant and malignant lesions using EUS
[76]
is 20% and using MRI/MRCP is 14% . EUS performs
better for small solid lesions and MRI for cystic lesions.
The current data from prospective observational studies
indicate that the diagnostic yield of neoplastic pancreatic
lesions varies significantly, depending if pre-cancerous
lesions (such as cysts, branch duct IPMN, main duct
IPMN) are included or not in the analysis, the screening
modality and the target population, being between
5% to 43%, whereas the detection rate for pancreatic
cancer is 2%. These data are consistent with the findings
from a recent systematic review of 542 high-risk indi­
[76]
viduals screened . Currently, screening programs are
recommended to be conducted only by experienced
clinicians in a research setting with prospective data
collection and close international collaboration.
PERILS, PITFALLS AND SUBTLETIES
IN THE DIAGNOSIS OF PANCREATIC
CANCER
With the use of multimodal imaging techniques and tissue
acquisition as described above, a definitive diagnosis of
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Zhang L et al . An update of current diagnostic modalities
pancreatic cancer can be made in the majority of patients
when suspicion arises. Nevertheless, there are a number
of situations where diagnostic findings are difficult
to distinguish from other benign conditions affecting
the pancreas. Accurate diagnosis in these settings is
crucial given the disparate therapeutic implications, and
generally relies on identifying and recognising radiological
or endoscopic subtleties, emphasising the importance of
close collaboration with expert centres.
Focal chronic pancreatitis
Focal chronic pancreatitis is a common mimicker
of pancreatic cancer. It can form a focal mass and
subsequently can cause pancreatic and biliary duc­
tal obstruction which may be indistinguishable in
[14]
appearance to that caused by ductal adenocarcinoma .
Standard imaging techniques including CT, MRI can be
inconclusive to distinguish the two in selected cases.
Depending on the degree of inflammation and fibrosis,
CE-EUS and elastography could help distinguish between
pancreatic adenocarcinoma and pseudotumoural chronic
pancreatitis. In these cases, EUS guided biopsy is
important and very close monitoring is recommended in
biopsy negative cases.
Autoimmune pancreatitis
Autoimmune pancreatitis clinically can present in a
similar fashion to pancreatic cancer; both most often
occurring in older persons typically aged over 60 years
and presenting as painless jaundice, new-onset diabetes
mellitus, and raised levels of serum tumour markers .
[77]
Serum IgG4 is frequently increased in autoimmune
pancreatitis, but occasionally can be mildly raised in 4%
[78]
to 7% of pancreatic cancers . However, the specificity
of IgG4 to autoimmune pancreatitis is strong, especially
when the serum IgG4 level is significantly raised to
[79]
at least twice the upper limit of normal . Typical CT
findings for autoimmune pancreatitis include a smooth,
diffusely enlarged homogenous gland with delayed
[78]
enhancement and capsule-like rim as seen in figure
5. However, autoimmune pancreatitis can also appear
[14]
as a mass on CT if there is focal involvement . PET/CT
with 18FDG has been shown to help differentiate these
two diseases, with diffuse pancreatic uptake of FDG and
concomitant uptake by salivary glands more suggestive
[80]
of autoimmune pancreatitis . Histopathologic evidence
from a biopsy via EUS-FNB can produce the most
definitive confirmation by demonstrating typical features
of autoimmune pancreatitis such as lympho-plasmacytic
sclerosing pancreatitis, abundant IgG4 positive cells,
idiopathic duct centric pancreatitis and/or granulocyte
[81]
epithelial lesion in the pancreatic duct . IgG4 staining
of the ampulla biopsy is also suggestive of autoimmune
pancreatitis. Finally, autoimmune pancreatitis is usually
sensitive to treatment with steroids, so a positive
therapeutic trial can be helpful in excluding pancreatic
[77]
cancer in equivocal cases .
Solid pseudopapillary neoplasm of the pancreas
Solid pseudopapillary neoplasm (SPN) is a rare indolent
2055 May 21, 2018|Volume 24|Issue 19|
 Zhang L et al . An update of current diagnostic modalities
A B
Figure 5 Multimodal imaging techniques demonstrating autoimmune pancreatitis in a patient. A: Diffuse enlargement “sausage shape” of the tail axial view on
CT; B: Head of the pancreas axial view in arterial phase on MRI; C: Tail of the pancreas T1-weighted axial view on MRI; D: Homogenous restricted diffusion on DWI
axial view MRI. CT: Computed tomography; MRI: Magnetic resonance imaging; DWI: Diffusion-weighted imaging.
neoplasm that has a low malignant potential and can be
cured with resection but can be difficult to differentiate
[82]
radiologically from pancreatic adenocarcinoma . SPN
usually occurs in younger women and is located in the
tail of the pancreas. MRI is better than CT in detecting
this tumour, with typical findings of an encapsulated
mass with solid and cystic components, as well as
[81]
haemorrhage without an obvious internal septum .
The typical EUS appearance is of mixed solid cystic lesion
with a median tumour size of 4.2 cm but sometimes it
can present as a solid mass. The diagnostic yield of CT
alone is 23%, EUS is 41% with a combined diagnostic
yield of 52%. EUS FNA significantly increased the
[83]
diagnostic yield to 82% .
It is also important to not incorrectly diagnose ade­
nocarcinoma in patients with SPN as there is a 5-year
survival rate of 96.9% post resection for SPN regardless
of the size of the tumour .
[82]
Annular pancreas
Annular pancreas is a rare congenital migratory
abnormality, with a reported incidence rate of up to 1 in
1000, and is due to incomplete rotation of the ventral
anlage around the duodenum that leads to the pancreas
[84]
encircling the second part of the duodenum . These
patients are asymptomatic and it is usually an incidental
finding on CT or MRI. An experienced radiologist
should be able to distinguish an annular pancreas from
a pancreatic mass, as a normal enhancing pancreas
and pancreatic duct encircling the second part of the
duodenum.
Pancreatic lipomatosis
Sometimes fatty replacement of the anterior portion
of the pancreatic head is seen in diabetes, obese or
elderly people. This can mimic a hypodense mass on
CT, however an MRI with in and out phases can exclude
the presence of a true mass by showing the presence of
[85]
intracellular fat .
PERSPECTIVES AND FUTURE
DIRECTIONS
Future research should focus on improving outcomes
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C D
in pancreatic cancer through the development of new
diagnostic techniques with higher diagnostic accuracy.
We should also aim to develop better tools to assess risk
for developing cancer thereby facilitating better targeting
of screening programs and better selection of patients
for surgery.
Apart from those already discussed, examples of
other promising novel diagnostic techniques that are
under research include needle based confocal laser endo­
microscopy (n-CLE), where a probe is passed through a
19-gauge EUS needle for real-time visua­lization of the
tissue at the microscopic level in the pancreatic cysts,
[86]
thus providing an optical biopsy . Similarly, probe
based confocal laser endomicroscopy (p-CLE) can be
used during an ERCP for indeterminate pancreato-biliary
[87]
stricture .
An ideal FNB needle design has not been found yet.
A recent study showed that fork tip needle had a higher
histologic yield than bevel needle but further studies are
[88]
needed to compare all types of FNB needles . Obtaining
adequate histological samples of the tumour during the
EUS is very attractive, as it can lead to enough samples
for DNA extraction, comprehensive whole exome
sequencing and next generation sequencing (NGS) of the
pancreatic tumour. A large amount of DNA will facilitate
preoperative genomic profiling and chemotherapy testing
and will play a role in individualised cancer treatment.
Mutation of the KRAS oncogene is present in 75%
to 95% of pancreatic cancer tissues. Combining EUS-
FNA cytology with KRAS mutation analysis on the biopsy
material can increase the pancreatic cancer accuracy
[89]
from 85% to 94% . This study shows promising results
particularly as EUS-FNB needles will continue to improve
and more material is obtained during the biopsy.
Detection of TP53 mutations in secretin-stimulated
pancreatic juice samples collected from the duodenum
of the patients with high grade dysplasia and pancreatic
[90]
cancer opens a new area of future research in diag­
nosis and potential screening for early pancreatic cancer.
EUS guided sampling of portal venous blood for circu­
lating tumour cells may enhance the ability to detect
occult metastatic disease, allowing improved patient
[91]
selection for surgery . Advances in these fields will be
most beneficial in improving the outcomes of patients
with pancreatic cancer.
2056 May 21, 2018|Volume 24|Issue 19|

Whole genome sequencing of pancreatic adeno­
carcinoma has found chromosomal rearrangements
leading to gene disruption and new candidate drivers
[92]
in pancreatic carcinogenesis . The development of
focus panel testing for pancreatic cancer is already
underway which will potentially allow tumour subtyping,
and may aid in the development of tumour specific
[93]
targeted therapies . These and other advances in
genetic understanding, including the identification of
several microRNAs involved in regulation of aberrant
cell replication, render them potential biomarkers for
diagnosis and prognosis .
[94]
CONCLUSION
While the early diagnosis of pancreatic cancer remains
challenging, improvements in diagnostic technology
and methodologies in the last decade will hopefully
translate into improved outcomes. Screening of high-
risk individuals using EUS and/or MRI is recommended
and shows promise in early detection. In patients with
suspected pancreatic cancer we propose the use of CT or
MRI as first-line investigations, with the choice between
the two being determined by cost, availability and local
expertise. Such cross-sectional imaging modalities
remain the gold standard for staging, both of the
primary lesion and detection of distal metastases. EUS
has become a powerful diagnostic modality and should
be used in adjunct, being superior in the detection of
small lesions and having the ability to obtain a tissue
diagnosis. While research is ongoing, at present there
is no role for the use of any routine biomarker in the
diagnosis of pancreatic cancer. Atypical cases can occur
and differentiation of malignant from benign pancreatic
lesions can be challenging; in these cases, opinion from
a radiologist with pancreato-biliary expertise should be
sought.
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 Ultrasound in Med. & Biol., Vol. 44, No. 6, pp. 1145–1154, 2018
Copyright © 2018 World Federation for Ultrasound in Medicine & Biology. All rights reserved.
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0301-5629/$ - see front matter

https://doi.org/10.1016/j.ultrasmedbio.2018.02.016

● Review

ULTRASOUND-GUIDED PERCUTANEOUS CORE NEEDLE BIOPSY FOR THE

DIAGNOSIS OF PANCREATIC DISEASE
Ying Huang, Jingwen Shi, Yun-Yun Chen, and Kao Li
Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China
(Received 20 October 2017; revised 21 February 2018; in final form 26 February 2018)

Abstract—Few studies have evaluated the performance of percutaneous core needle biopsies of the pancreas. This
article is an overview of the advantages, disadvantages, predictive power and complications associated with per-
cutaneous ultrasound-guided core needle biopsies of pancreatic lesions. A comprehensive literature search of Medline
(using PubMed as the search engine) and EMBASE was done to identify suitable studies up to March 2017. A
study of quantitative pre-operative pancreatic biopsy data was reported. Lesion location, mean or median number
of passes, inadequate tissue or technical failures and complications were assessed for all cases by reviewing clin-
ical notes and post-procedural imaging. The analysis included 13 studies, mostly of a retrospective nature. The
sensitivity (mean: 94.42%, range: 90%–100%) and specificity (mean: 97.94%, range: 94.7%–100%) of the pro-
cedure were high, and the mean accuracy of diagnosis was 95.76 (range: 91–100). Furthermore, the procedure
had a high negative predictive value of approximately 76.26%. Of the 13 reported studies, 7.3% were inade-
quate or technical failure cases. The mean rate of complications was 2.08%, which seemed similar to the lower
limit of this rate for endoscopic ultrasound-guided fine-needle aspirations. The risk of tumor seeding with ultrasound-
guided core needle biopsies was not reported in the included articles. With the development of technology, ultrasound-
guided percutaneous core needle biopsy for pancreatic lesions is increasingly available and has optimal diagnostic
power in pancreatic neoplasms. (E-mail: huangying712@163.com) © 2018 World Federation for Ultrasound in
Medicine & Biology. All rights reserved.
Key Words: Biopsy, Large-core needle, Pancreatic, Percutaneous, Ultrasonography, Interventional.

INTRODUCTION Biopsy can be performed intra-operatively (Ingram

et al. 1978; Moossa and Altorki 1983), endosonographically
Pancreatic cancer is a fatal disease with a poor progno-
(Brugge and Van Dam 1999) or percutaneously under com-
sis, which is due partly to delayed diagnosis because of
puted tomography (CT) (Harter et al. 1983) or
the late onset of symptoms (Jemal et al. 2009). So early
ultrasonography (US) guidance, respectively (Hancke et al.
detection and accurate staging are vital in choosing the
1975; Mitchell et al. 1989). US-guided percutaneous biopsy
appropriate treatment.
is often used and is suitable for the diagnosis of pancre-
Solid pancreatic lesions detected by imaging exami-
atic pathology or the rejection of pancreatic allograft for
nations include cancer, focal pancreatitis, tuberculosis,
four reasons (Atwell et al. 2004). First, on sonography, real-
lymphoma and metastases. However, some of these lesions
time imaging and multiplanar monitoring are displayed as
cannot be easily distinguished by laboratory testing and
the biopsy needle traverse tissues along the path to the
imaging (Neff et al. 1984; Podolsky et al. 1981). Even so,
lesion. Second, the high spatial resolution of US imaging
pre-operative staging must provide reliable information on
has led to its ever-increasing use in pancreatic interventional
the extent of the cancer. In this case, pancreatic biopsy is
procedures. Third, compared with endoscopic ultra-
often required for initial diagnosis of pancreatic masses
sound (EUS), percutaneous US scanning can reveal a wider
before chemotherapy or radiotherapy (Hartwig et al. 2009;
observed area in a single view without gas interference.
Itani et al. 1997).
Similarly, EUS-guided biopsies may not be suitable for
lesions in the body (Kahriman et al. 2016), tail or deep
regions of the pancreas (Hartwig et al. 2009), which are
inaccessible with the high-frequency probe and cannot be
Address correspondence to: Ying Huang, Department of Ultrasound,
Shengjing Hospital of China Medical University, Shenyang, 110004, China. evaluated (Wei et al. 2015). Fourth, unlike CT, which is
E-mail: huangying712@163.com time consuming and exposes both patients and radiologists

1145
1146 Ultrasound in Medicine & Biology
to significantly increased radiation doses, US may be more
convenient and its widespread adoption not limited.
On the other hand, tissue acquisition is important in
confirming the diagnosis and guiding the treatment of a
pancreatic mass. Despite its extensive use, fine-needle as-
piration (FNA) is limited because it only provides a
cytologic specimen with few histologic structures, which
prevents a complete tissue analysis for diagnosis and clas-
sification (Hebert-Magee 2015). Another limitation of FNA
is the uncertain number of passes required to acquire suf-
ficient sample without a standby cytopathologist (Kedia
et al. 2013). A core needle biopsy (CNB) specimen can
theoretically overcome FNA-related limitations and have
higher diagnostic accuracy, because it provides well-
preserved tissue structure for histologic evaluation.
Percutaneous CNBs have been performed since 1980;
however, few studies have evaluated their performance. In
addition, there exists a dilemma in that the potential com-
plications of percutaneous biopsy such as hemorrhage,
pancreatitis, tumor seeding and fistulas outweigh its po-
tential benefits. This relative paucity of data makes it
difficult to compare CNB results directly with the results
of EUS-guided biopsy.
What follows is a review of the advantages, disad-
vantages, predictive power and complications related to
percutaneous US-guided CNB of pancreatic lesions.
SEARCH STRATEGY AND STUDY SELECTION
A comprehensive literature search of Medline (using
PubMed as the search engine) and EMBASE was done
to identify suitable studies up to March 2017. The search
was based on the following combinations of Medical
Subject Heading terms, EMtree terms and text words and
was restricted to English publications: “biopsy” AND (“ul-
trasonography” or “ultrasonics” or “ultrasound” or
“echography”) AND (“pancreas” or “pancreatic”) AND
“percutaneous.” The bibliographies of retrieved articles were
searched manually to identify relevant studies.
Study selection
All stages of study selection and data abstraction were
conducted independently by two reviewers (Y.H. and J.S.).
Search findings were screened for potentially qualified
studies. Abstracts and full articles were obtained for de-
tailed evaluation; qualified trials were included.
Data extraction
The search initially identified 282 potential titles and
abstracts; of these, 192 irrelevant citations were ex-
cluded after an initial review of titles, and the remaining
90 references were retrieved as full-text articles for further
assessment. An additional 56 had to be excluded by ab-
stract review for a variety of reasons. Two records were
Volume 44, Number 6, 2018
included by manual search references or by use of the
related articles function in PubMed. Twenty-three studies
were excluded after in-depth review, leaving 13 studies that
fulfilled the criteria for inclusion (Fig. 1).
Four studies evaluated the diagnostic accuracy of per-
cutaneous US-guided core needle biopsy of pancreatic
masses (Bhatti et al. 2016; Kahriman et al. 2016; Mitchell
et al. 1989; Yang et al. 2015). One of the four studies di-
rectly compared the tolerability and efficacy of US-
guided core biopsy versus FNA (Yang et al. 2015). One
study evaluated percutaneous biopsy of the pancreas under
contrast-enhanced ultrasound (CEUS) guidance (Wei et al.
2015). Eight studies provided data on percutaneous US-
guided biopsy of pancreas allograft (Atwell et al. 2004;
Gaber et al. 1992; Klassen et al. 2002; Kuo et al. 1997;
Lee et al. 2000; Malek et al. 2005; Stephens et al. 2012;
Wong et al. 1996).
Quantitative data on the respective sensitivity, speci-
ficity, negative predictive value and accuracy were extracted
from five primary studies. Date of publication, country of
origin, prospective or retrospective design, number of
centers, length of study, age, gender, needle types and
sample size were tabulated systematically (Table 1). Further
information extracted from each article included lesion lo-
cation, mean or median number of passes, inadequate tissue
or technical failures and complications for all cases.
All included studies were published between 1989
and 2016. The samples analyzed contained 12 to 250 par-
ticipants. Two trials were prospective, randomized
comparisons. The remaining studies were based on pre-
dominantly retrospective analyses of prospectively collected
data or on retrospective identification of biopsy samples
of patients who underwent biopsy. All reports contained
results of single-center series.
US-GUIDED PERCUTANEOUS PANCREATIC
BIOPSY TECHNIQUES
Compared with CT-guided biopsy (Lee et al. 1998),
in US-guided percutaneous biopsy, the insertion points in
the skin through which the pancreas is accessed can be
chosen more freely, either sagittally or transversely. To avoid
damage to important structures, such as the gallbladder
and hepatic and gastroduodenal arteries, the ideal inser-
tion point, especially for diagnostic purposes, is the left
upper quadrant, left of the midline. Manual compression
is often applied to the abdominal wall to avoid needle access
into hollow organs. Transgastric passage is commonly used;
transcolonic passage should be avoided. However, the in-
sertion points for other therapeutic interventional aims
should be chosen based on the location of each individ-
ual lesion.
Two types of probes are used for interventional pro-
cedures: those with lateral support and those with
 Percutaneous CNBs for pancreatic disease diagnosis ● Y. Huang et al. 1147

Fig. 1. Flowchart of the process of selection of eligible studies in the systematic review. FNA = fine needle aspiration,
US = ultrasound.

Table 1. Characteristics of the selected studies

Duration Age range No. of Needle
Authors Year Country Design Center (y) (mean) Gender biopsies/persons (gauge)

Bhatti et al. 2016 UK R 1 12 (2003–2015) 34–85 (68) 78 M/75 F 153 B/153 P 16–20
Kahriman et al. 2016 Turkey R 1 6 (2009–2015) 16–88 (64.3) 150 M/100 F 250 B/250 P 18
Yang et al. 2015 Canada R 1 10 (2001–2011) 29–87 (66) 43 M/45 F 88 B/88 P 18
Mitchell et al. 1989 UK R 1 NR 36–74 19 M/14 F 33 B/33 P 18
Wei et al. 2015 China P 1 4 (2009–2013) 27–82 (56.1) 28 M/23 F 53 B/51 P 18
Stephens et al. 2012 UK NR 1 2 (2008–2010) NR NR 25 B/15 P NR
Malek et al. 2005 USA NR 1 1 (2002) NR NR 120 B/54 P 18
Atwell et al. 2004 USA R 1 4 (1998–2002) 20–61 (39) 43 M/45 F 232 B/88 P 18 (98.3%)
Klassen et al. 2002 USA NR 1 8 (1992–2000) NR NR 426 B/183 P 18 G
Lee et al. 2000 USA R 1 5 (1993–1998) 22–52 (39.1) 12 M/9 F 42 B/21 P 18 G, 20 G
Kuo et al. 1997 USA R 1 2 (1993–1995) NR NR 55 B/35 P NR
Wong et al. 1996 USA P 1 2 (1993–1995) 24–57(37.9) 21 M/15 F 51 B/36 P 18 G
Gaber et al. 1992 USA NR 1 NR NR NR 15 B/12 P 18 G

P = prospective, R = retrospective, B = biopsy, P = person, NR = not reported.

discontinuous crystals and central support. The needle sup-
ports are fixed laterally or centrally are different in caliber
and have different insertion points or positions, which cor-
respond to the angle chosen on the basis of imaging. If
the puncture access is not straight or to avoid some im-
portant organs during the process of puncture, the curve
access is more flexible without guide kits for the free-
hand technique. Any tracks can be used to reach the target
in the safest possible manner.
ROLE OF PERCUTANEOUS BIOPSY IN
VARIOUS PANCREATIC PATHOLOGIES
Diagnostic procedures for pancreatic mass: Benign or
malignant
The discussion that follows considers the evidence
available from published trials and series that have as-
sessed the sensitivity, specificity, negative predictive value
and accuracy of pancreatic biopsies (Table 2).
1148 Ultrasound in Medicine & Biology Volume 44, Number 6, 2018

Table 2. Sensitivity, specificity, negative predictive value and accuracy of percutaneous ultrasound-guided core needle biopsy
of pancreatic masses: Results of studies published since 1989*
Authors Year No. of biopsies Inadequate/AS (%) Sensitivity (%) Specificity (%) NPV (%) Accuracy (%) Diagnostic rate (%)

Bhatti et al. 2016 153 3.9 90 95 42 91 92

Kahriman et al. 2016 250 8 99 94.7 94.7 98.4 92
Wei et al. 2015 53 3.8 90.48 100 84.6 96.08 96.23
Yang et al. 2015 88 4.5 92.6 100 60 93.3 93.3
Mitchell et al. 1989 33 6 100 100 100 100 94
Median 115.4 5.24 94.416 97.94 76.26 95.756 93.506

Inadequate/AS = inadequate tissue or technical failure/atypical or suspicious, NPV = negative predictive value.
* Diagnostic performance (with 95% confidence intervals) derived from the 2 × 2 tables of individual studies.

In general, the sensitivity (mean = 94.42%, range:
90%–100%) and specificity (mean = 97.94, range: 94.7%–
100%) of the tests were high, and the mean accuracy of
diagnosis was 95.76% (range: 91%–100%). The diagnos-
tic rate (mean = 93.51%, range: 92%–96.23%) depends not
only on the expertise of the pathologist, but also on the
adequacy of the samples provided. Furthermore, percu-
taneous CNB has been associated with a high negative
predictive value of approximately 76.26%. The predic-
tive power of percutaneous US-guided core needle biopsies
of pancreatic lesions was very good.
Percutaneous US-guided biopsy of pancreas allograft
It is difficult to monitor pancreatic allograft rejec-
tion, especially in patients who have undergone
transplantation of only the pancreas and patients who have
undergone pancreas transplantation after kidney trans-
plantation. In these patients, renal function cannot be used
as a measure of pancreatic allograft status, unlike in pa-
tients undergoing simultaneous pancreas and kidney
transplantations. Laboratory tests of pancreatic function,
including serum and urinary levels of amylase and serum
levels of glucose, are non-sensitive and non-specific for
rejection, and hyperglycemia usually occurs only in late
rejections (Allen et al. 1991; Casanova et al. 1993; Munn
et al. 1990). Because of the lack of sensitivity and speci-
ficity associated with other rejection measurements, the
pancreas is usually assessed by histologic biopsy.
Percutaneous US-guided biopsy for histologic ex-
amination is a recognized technique. The method was
described by Allen et al. (1991), and researchers have con-
tinued to have good success rates in obtaining allograft
tissue. Lee et al. (2000) achieved an overall success rate
with US-guided biopsy alone; sufficient tissue was ob-
tained in 89% of the procedures. Klassen et al. (2002)
reviewed 426 US-guided biopsies performed by
nephrologists at their institution. By rigorously defining
tissue adequacy, they achieved a success rate of 88% using
an 18-gauge (G) biopsy needle.
In addition to rejection, other important clinical en-
tities can be diagnosed by percutaneous pancreas allograft
biopsy, such as islet cell toxicity caused by tacrolimus and
cyclosporine, cytomegalovirus allograft pancreatitis and
lymph proliferative disease after pancreas allograft
(Drachenberg et al. 1998, 1999; Klassen et al. 2000). These
uncommon clinical entities are important to consider in
the diagnosis and treatment of pancreas allograft
dysfunction.
New application of contrast-enhanced ultrasound in
pancreas biopsy
There have been some new applications of percuta-
neous core needle biopsy of the pancreas. As is known,
the guidance provided by B-mode US may not be suit-
able for large tumors with non-liquid necrotic tissue, hypo-
echoic severe fibrosis, pancreatic local swelling or poorly
visible small lesions. Therefore, the injection of contrast
medium to identify the viable portion of a pancreatic tumor
is considered useful when performing a diagnostic biopsy
(Wei et al. 2015). Wei et al. (2015) used CEUS to depict
tumor angiogenesis and neo-angiogenesis, which better vi-
sualized pancreatic lesions not clearly observed by gray-
scale US (Piscaglia et al. 2012). Their results indicated that
percutaneous CEUS-guided biopsy of the pancreas is fea-
sible for targeted pancreatic lesions that are not definitively
positioned by gray-scale ultrasound.
EFFECT OF THE POSITION OF THE
PANCREATIC LESION ON PERCUTANEOUS
BIOPSY ACCURACY
The accuracy of percutaneous diagnostic proce-
dures reported in the literature also varies according to the
location of the lesion: 93%–94% accuracy is reported for
lesions in the body and tail of the pancreas, slightly higher
than what is reported for pancreatic head lesions (83%–
84%) (Brandt et al. 1993; Mallery et al. 2002). However,
in a series of 135 percutaneous diagnostic procedures per-
formed in 2004 (D’Onofrio et al. 2007), 113 (84%) of the
samplings were positive. Of the 22 non-diagnostic sam-
plings, 16 (73%) were of lesions located in the head or
the uncinate process and 6 (27%) were in the body or tail.
The percutaneous biopsy technique has been pro-
posed as the easiest and most sensitive for detecting
 Percutaneous CNBs for pancreatic disease diagnosis ● Y. Huang et al. 1149

malignancies when the lesion is large and located in the

Accuracy

89.25
(%)

90.5
pancreatic body or tail (Brandt et al. 1993). However, Yang

88
et al. (2015) found no statistically significant difference
in any of the parameters between samples obtained from
the head and neck and those from the body and tail

NPV

11.5
(%)

23
0
(p > 0.05).
From the evidence available in published papers, it

Specificity
is clear that the diagnostic rate, sensitivity, specificity, neg-

97.5
(%)
ative positive value and accuracy for percutaneous biopsy

95
100
of lesions in the pancreatic head are higher than the values
for biopsy of the pancreatic body and tail (Table 3).

Sensitivity

88.75
(%)

90.5
DIFFERENT NEEDLES USED IN

87
PERCUTANEOUS PANCREATIC BIOPSY

Table 3. Accuracy of percutaneous core needle biopsy according to lesion site in pancreas*
Needles used in the diagnosis of pancreatic lesions

Diagnostic
rate (%)
differ for cytologic and histologic samplings. For biop-

95.2
88.1
81
sies of the pancreas, needles ranging from 14G to 25G are
commonly used. FNA needles, with a 23G to 20G caliber,
have an internal stiletto that can be removed so that the

(body/tail)
Location
material is suctioned by capillarity or aspiration effect. FNA

21
13
17
samples are suitable for cytologic evaluation, whereas 14G
to 19G needles (core biopsies) are used to obtain tissue
samples for histopathological analysis. Devices for core
biopsies include cutting needles, which are manually trans-

Accuracy

* Diagnostic performance (with 95% confidence intervals) derived from the 2 × 2 tables of individual studies.
93.8
93.4
(%)
ferred back and forth within the lesion to obtain histologic

93
samples, and automated “biopsy guns.” Because core biopsy
samplings are always longer than 1 cm, lesion diameter
should be at least 1 cm, preferably 2 cm. Care should be

56.35
NPV
(%)

66.7
taken not to pass samples through medium-size arteries 46
or the colon, which may lead to an increased bleeding, peri-
tonitis or abscess formation. Thus, FNA is generally
Specificity
(%)

100
100
100

preferred when sampling sites adjacent to major bloods

vessel or passing needles through the bowel wall.
The different needles used in biopsy differ in diag-
nostic ability. Some researchers have pointed out that
Sensitivity

91.95

although more tissue is usually acquired in core biopsy

(%)

92.9
91

than in FNA, the rates of diagnosis of most malignan-

cies have not been reported to be superior (Amin et al.
2006; Karlson et al. 1996; Stewart et al. 2002; Zech et al.
Diagnostic
rate (%)

2002). Others argue that core needle biopsy is more sen-

93.8
93.9
94

sitive than FNA in the diagnosis of a pancreatic lesion

(Brandt et al. 1993; Tyng et al. 2015). Previous studies
reported that percutaneous US-guided pancreatic CNB and
Location

FNA are both tolerable and effective methods for the di-
(head)

88.5
132
45

NPV, negative predictive value.

agnosis of pancreatic lesions, with sensitivities as high as

93% for CNBs (Elvin et al. 1990; Jennings et al. 1989;
Karlson et al. 1996; Matsubara et al. 2008; Paulsen et al.
2016
2015
Year

2006; Yang et al. 2015) and 67% to 99% for FNAs (Bhatia
et al. 2008; Bret et al. 1986; Di Stasi et al. 1998;
Hall-Craggs and Lees 1986; Mallery et al. 2002; Matsubara
Bhatti et al.
Yang et al.

et al. 2008; Volmar et al. 2005; Yang et al. 2015; Zamboni

Authors

Median

et al. 2009). However, no large study comparing these two

techniques in pancreatic lesions has been identified.
1150 Ultrasound in Medicine & Biology Volume 44, Number 6, 2018

Table 4. Passes, inadequate/AS and major complications of percutaneous ultrasound-guided core needle biopsy of
pancreatic masses
Incidence
of major
No. of Inadequate/AS complications
Authors Year biopsies Passes (%) (%) Description of major complications

Bhatti et al. 2016 153 1 (83%) 3.9 2 1 death from overwhelming hemorrhage
2 patients with morbidity (hematoma and cerebrovascular
accident)
Kahriman et al. 2016 250 NR 8 1.6 1 pseudoaneurysm of the gastroduodenal artery
3 cases of acute pancreatitis
Wei et al. 2015 53 3 3.8 1.9 1 biliary peritonitis
Yang et al. 2015 88 NR 4.5 0 None
Stephens et al. 2012 25 NR 8 4 1 case of mild, self-limiting allograft pancreatitis
Malek et al. 2005 120 1–3 15 1.7 1 patient with bleeding that required admission and transfusion
of 3 units of packed red blood cells, but no surgical intervention
was necessary
1 patient with pancreatic fistula that healed with non-operative
management
Atwell et al. 2004 232 2 (84.5%) 3.9 2.6 3 cases of intra-abdominal hemorrhage
1 case each of gross hematuria, allograft pancreatitis and severe
pain requiring overnight hospitalization; 2 of the 4 bleeding
complications occurred while patients were receiving
therapeutic aspirin
Klassen et al. 2002 426 2.3 (1–11) 12 2.8 Including 8 episodes of bleeding, 5 of which required surgical
intervention and one possible extra-graft exocrine leak
Other complications included inadvertent liver (1), kidney (1) and
small bowel (1) biopsy
Lee et al. 2000 42 2.6 (1–4) 7.1 2.4 Local, mild bleeding at the biopsy site in 1 case
Kuo et al. 1997 55 NR 11 0 None
Wong et al. 1996 51 1 or 2 0 2 1 patient (1 y from transplant) developed acute abdominal pain
and was found at laparoscopy to have bled from an omental
vessel adherent to the pancreas; the bleeding resolved
spontaneously without further treatment
Gaber et al. 1992 15 NR 13.3 0 None
Mitchell et al. 1989 33 NR 6 6.1 2 severe abdominal pain
Median 118.6923077 7.423076923 2.084615385

Inadequate/AS = inadequate tissue or technical failure/atypical or suspicious.

Fine-needle aspiration of the pancreas is a simple, cost-
effective, relatively low-risk and high-accuracy diagnostic
procedure (Dodd et al. 1997). However, its diagnostic ac-
curacy is limited by the availability of an onsite
cytopathologist (Ecka and Sharma 2013; Roy et al. 2016;
Song et al. 2010), and it is less sensitive in the diagnosis
of malignant tumors associated with chronic pancreatitis
(Varadarajulu et al. 2005). In addition, tumors such as lym-
phomas and stromal cell tumors may be difficult to
diagnose because of the need for accurate pathologic as-
sessment of tissue structure and morphology (Levy and
Wiersema 2005).
In studying different core needle types, the 20G needle
was found to be highly efficient (Lee et al. 2000). Twenty-
gauge needles had slightly higher success rates in acquiring
sufficient tissue for pathologic assessment (83%) and were
associated with lower complication rates (7%). Eighteen-
gauge needles were slightly less effective in acquiring
adequate tissue (76%) and were associated with higher
complication rates (15%). Although incomplete, the data
on 20G needles do indicate that the smaller 20G needle
can be as effective as the 18G needle in sampling pan-
creatic tissue, with a lower incidence of complications. But
so far, the 18G core needle is the dominant type used for
percutaneous biopsy of the pancreas.
Thirteen studies reported 7.42% cases of inadequa-
cy or technical failure (Table 4). There is no doubt that
larger-caliber needles designed specifically to acquire more
tissue would facilitate subsequent molecular biological anal-
ysis and histologic grading.
HISTOLOGY AND CYTOLOGY
Once the pancreatic lesion has been reached, the cy-
tologic sampling needle is moved in and out with very small
amplitude from the center point. When suction is neces-
sary, a 10-mL syringe suitable for aspiration is applied to
the needle. To be most effective, percutaneous imaging-
guided FNA requires experienced radiologists and
cytopathologists (Harter et al. 1983). In addition, the pres-
ence of a cytologist allows for the immediate preparation
and reading of the sample. Immediate responses on sampled
 Percutaneous CNBs for pancreatic disease diagnosis ● Y. Huang et al.
material determine the subsequent steps of the diagnos-
tic procedure: If the material is insufficient, the FNA must
be repeated or a biopsy performed. However, even expe-
rienced personnel find it challenging to diagnose pancreatic
adenocarcinoma from cytologic samples (Gazelle and
Haaga 1991). In addition, if the specimens are not repre-
sentative, percutaneous FNA is associated with a
considerable false-negative rate of approximately 30%
(Spier et al. 2009). Therefore, the negative predictive value
of percutaneous pancreatic biopsy must be recognized.
As an alternative, percutaneous automated core needle
biopsy can eliminate the need for experienced
cytopathologists at the time of the procedure. A core needle
biopsy is superior in diagnostic quality and provides more
tissue compared with an FNA sample, avoiding the need
for more needle passes. Tissue biopsy is usually per-
formed to confirm the histopathologic features of a lesion
before palliative treatment, especially when molecular or
hereditary oncologic therapies are used.
COMPLICATIONS OF NEEDLE BIOPSIES
With the percutaneous biopsy technique, there is a
greater risk of complications, including intra-abdominal
hemorrhage, macrohematuria, allograft pancreatitis, exo-
crine leak and inadvertent biopsy of other organs (Atwell
et al. 2004; Gaber 2007; Klassen et al. 2002; Lee et al.
2000). Bleeding is usually self-limiting and merely re-
quires transfusion. Although most cases are mild, acute
pancreatitis may delay surgery, meaning the originally re-
sectable tumor could not be removed (Eloubeidi et al.
2004).
Theoretically, the size of the needle and the number
of passes made may also affect the overall risk of com-
plications. At present, there is insufficient research to assess
definitively whether needle passes can affect the risk of
adverse events. From the data, most commonly one or two
needle passes made in percutaneous biopsy (Table 4). It
is recommended that the diagnosis be made with the least
number of passes to avoid unnecessary risks.
Similarly, greater tissue trauma is expected when using
a cut needle instead of a suction needle. The incidence of
complications rates for core needle and FNA biopsies
ranged from 2.6% to 21% (Elvin et al. 1990; Matsubara
et al. 2008; Paulsen et al. 2006) and from 1.5% to 20%
(Di Stasi et al. 1998; Matsubara et al. 2008; Zamboni et al.
2009), respectively, in the different studies. However, Brandt
et al. (1993) reported that in their series, both thick-
gauge and thin-gauge needles caused minor complications
and that the use 21G and 22G needles may lead to major
complications. The effect of needle gauge on the likeli-
hood of complications might be related to the sampling
mechanism. According to this view, the average inci-
dence of complications of percutaneous core needle biopsy
1151
is very low, 2.08%, which is similar to the lower limit of
EUS-guided FNAs (Table 4).
The risk of tumor seeding with US-guided CNB was
not reported in the articles included in this review, though
several layers of other tissue structures are traversed in the
percutaneous approach (Table 4). In the largest cohort study
(Bhatti et al. 2016) to date, biopsies were used mainly to
determine palliative treatment for malignant tumors, and
there was no evidence of peritoneal seeding in patients in
the cohort. In addition, a coaxial technique may be pref-
erable to reduce the number of punctures and the risk of
implantation by separating the adjacent tissue from the
needle (Maturen et al. 2006).
The National Comprehensive Cancer Network
(NCCN) guidelines state that EUS-guided FNA is supe-
rior to CT-guided FNA in patients with resectable disease
because of the better diagnostic yield, better tolerability,
and potentially lower risk of peritoneal seeding with EUS-
FNA compared with the percutaneous approach (Brugge
et al. 2014; Micames et al. 2003; Okasha et al. 2013).
However, on the basis of recent research results and with
the development of the technique, US-guided percutane-
ous core needle biopsy for pancreatic lesions is promising.
OVERVIEW
Many clinicians believe that histologic assessment
cannot be recommended because of the risks of bleeding
and tumor seeding. Appropriate pre-planning, patient prep-
aration and compliance with strict procedures can minimize
the risks associated with biopsy. For the seeding problem,
tissue sampling was performed using either a coaxial or
tandem needle technique. The coaxial needle is com-
posed of an outer cannula and an inner stylet, which are
inserted into the lesion together, after which the inner
stylet is removed and the smaller needle is introduced
into the larger needle. Thus, the inner biopsy needle is
used to acquire the samples needed. In the tandem needle
technique, the biopsy needle reaches the lesion parallel
to the piercing needle which was placed next to the lesion
earlier. The samples are acquired through the cannula after
removal of the inner stylet of the biopsy needle (Fig. 2).
Both techniques avoid the risk of seeding (Hahn et al.
1995).
The risk of bleeding increases with needle size, but
biopsy techniques are heavily dependent on the experi-
ence of the interventional radiologist, and a veteran could
overcome the corresponding biopsy risk. Therefore, with
the development of technology, US-guided percutaneous
core needle biopsy for pancreatic lesions is increasingly
available and has optimal diagnostic power in pancreatic
neoplasms.
As targeting of small masses with US-guided per-
cutaneous biopsy is difficult, and this is an advantage of
1152 Ultrasound in Medicine & Biology Volume 44, Number 6, 2018

Fig. 2. Schematic summaries of the coaxial and tandem needle techniques. The coaxial needle was composed of an outer cannula
and an inner stylet, which were inserted into the lesion together. After placement in the lesion, the inner stylet was removed,
and a smaller needle was introduced inside the larger one. Thus, the inner biopsy needle was used to acquire the samples needed
(upper panels). In the tandem needle technique, the biopsy needle reaches the lesion parallel to a piercing needle that had been
introduced next to the lesion earlier. Samples were obtained through the cannula after removal of the inner stylet of the biopsy
needle (lower panels).

EUS guidance over US guidance as small masses are some-
times concealed by gases.
Acknowledgments—The study was supported by grants from the Na-
tional Natural Science Foundation of China (No. 81371552).
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PROCEDURES PRO > DIAGNOSTICS / SURGERY > PEER REVIEWED

Pancreatic Biopsy

J. Brad Case, DVM, MS, DACVS

W. Alexander Fox-Alvarez, DVM
University of Florida

Antemortem diagnosis of pancreatic
disease is a challenge. Histopathology
remains the gold standard of diagnosis
for pancreatic neoplasia and pancreatitis.
Pancreatic biopsy provides a definitive
diagnosis of pancreatitis, assuming a rep-
resentative sample is obtained. An open
or laparoscopic approach can be made to
collect samples.
Open approaches require only standard
surgical equipment and allow easy man-
ipulation of tissue and visualization of the
entire pancreas (important when sam-
pling focal disease involving the left limb).
However, open surgery results in greater
tissue injury and pain compared with a
laparoscopic approach and may not be
favored by some clients or in some cases.
Studies in both human and veterinary
medicine have demonstrated laparoscopic
procedures to have less tissue trauma and
systemic inflammation, lower pain indi-
ces, and reduced patient convalescence
when compared with analogous proce-
dures performed using an open approach.
This decrease in the healing and inflam-
matory demand postoperatively may be

continues

What You Will Need A

Guillotine Biopsy via Laparotomy
n Basic surgery pack (ie, needle
B C D
holders, DeBakey thumb forceps,
mosquito hemostats, Metzenbaum
scissors)

Laparoscopic Biopsy
n Videolaparoscopy tower (A), camera
(B), insufflation tubing (C), and light E
cable (D)
n 2 5-mm trocars and cannulas (E)

n 5-mm laparoscopic clamshell biopsy

forceps (F)
n 5-mm laparoscope 0° (G)

n 5-mm laparoscopic blunt probe (H)

F
Both Methods
n Sterile sample cups for separate
diagnostic samples (histopathology,
culture) G
n Culture media
H
n 10% formalin for histopathology

n Microscope slides for impression

cytology

March 2015 • Clinician’s Brief 19

PROCEDURES PRO

particularly important in patients with STEP-BY-STEP n GUILLOTINE METHOD VIA LAPAROTOMY

delayed healing from metabolic derange-
ments, such as hypoproteinemia, second- STEP 1
ary to their pancreatic disease. While this
Place patient in dorsal recumbency position and follow standard aseptic
approach provides a magnified, illumi-
nated view of the right limb of the pan- preparation.
creas, the left limb of the pancreas is
difficult to evaluate laparoscopically and
may require dissection of the omental
bursa and repositioning of the patient
(beyond the scope of this article). In addi-
tion, laparoscopy requires the use of spe-
cialized equipment and may take slightly
longer to perform for learning practi-
tioners; however, once the procedure can
be completed with confidence, the time
required can be comparable with that for
an open method.

STEP 2
When biopsying the pancreas, if not tar-
geting a specific lesion, the distal aspect Surgical approach. If only the pancreas is to be evaluated, a midline cra-
of the right or left limb of the pancreas is nial abdominal approach can be made. Neoplasia is a differential diagnosis
preferred to decrease the risk for damag- for pancreatic disease, and it is usually advisable to explore the entire
ing important vascular and pancreatic abdomen to evaluate for evidence of pathology in other organs.
structures. Care should be taken to avoid
major blood vessels (eg, caudal pancreati-
coduodenal artery and its branches).

Pancreatic biopsy is a safe procedure.

Despite concerns for adverse sequelae
after pancreatic biopsy, studies suggest
that significant clinical or biochemical
abnormalities are uncommon postopera-
tively.1-4 Patients should be monitored
closely for signs of pancreatitis.

Cranial abdominal approach to the pancreas.

20  cliniciansbrief.com • March 2015

 STEP 3

Exploration and pancreatic biopsy. Evaluate the abdominal viscera and perito-
neal surfaces. Abnormal tissue should be sampled for histopathology. The right
pancreatic limb is contained within the mesentery of the duodenum, which is
used for indirect manipulation of the pancreas. Expose the pancreas and evalu-
ate for gross abnormalities. Isolate a 5-mm area of the pancreatic lesion or distal
right limb (if diffuse disease), and place an encircling ligature in guillotine fashion
(similar to liver biopsy; A and B).
Alternatively, the omental bursa can be opened and the epiploic foramen
entered to access the left pancreatic limb for biopsy. To gain access to the left
pancreatic limb, retract the stomach ventrally, using an assistant’s fingers or a
pair of atraumatic Babcock forceps. The entire pancreas (left limb, angle, and
right limb) can be revealed if the spleen is retracted in a ventral and cranial direc-
tion. Once the desired pancreatic location has been selected, tighten the ligature
to crush the pancreatic parenchyma and to ligate small pancreatic vessels. If dif-
fuse pancreatic disease is present, use the distal tip of the left limb for sampling
to avoid pancreatic ducts. Collect the biopsy specimen transecting tissue distal
to the ligature with a scalpel blade.

A B

Guillotine suture being placed (arrow). Handle biopsy sample gently to Pancreatic biopsy has been removed and no bleeding is observed.
avoid crushing.

STEP 4

Control hemorrhage and close. Hemorrhage is typically avoided because of the Author Insight
encircling ligature. If residual bleeding occurs, it can be controlled using 3 to 5 Large malleable retractors and
minutes of steady digital pressure or a plug of hemostatic gelatin foam. Evaluate laparotomy sponges are useful to
the abdomen for hemorrhage. Close the abdomen routinely. retract the visceral surface of the
stomach to improve exposure during
biopsy of the left pancreatic limb.

continues

March 2015 • Clinician’s Brief 21

PROCEDURES PRO

STEP-BY-STEP n CLAMSHELL BIOPSY FORCEPS METHOD VIA LAPAROSCOPY

STEP 1

Position patient. Reverse Trendelenburg position (ie,
dorsal recumbency, body tilted with head up and feet lower
than head, at approximately 15 degrees) with leftward
obliquity is the authors’ preferred position for descending
limb pancreatic biopsy.
Many endoscopists, however, prefer a right lateral approach
as it provides an immediate view of the pancreas. The
major disadvantage of the right lateral approach is the lack
of ability to view the entire liver, which is often indicated
given the possibility of concomitant inflammatory or neo-
plastic disease and limitations of ultrasonography.
The approach described here can provide excellent visual-
ization of the duodenum, liver, extrahepatic biliary system,
right kidney, and right limb of the pancreas. The left limb of
the pancreas is challenging to view laparoscopically and
should not be attempted without significant training and
experience.

Reverse Trendelenburg and left lateral oblique position. Black lines represent the patient’s position in reverse Trendelenburg and left lateral obliquity.

STEP 2

Surgical approach. Place the initial port 1 to 2 cm caudal to the umbilicus. Port Author Insight
placement is achieved after making an incision through the skin no longer than
Following initial port insertion,
the diameter of the cannula. Continue the incision to the linea alba. A Veress nee-
place all subsequent ports under
dle, 5-Fr catheter, or Hasson method can be used to achieve pneumoperitoneum.
laparoscopic visualization. Once both
Place apposing stay sutures at the margins of the linea. Use a number 11 blade to ports have been placed, reduce the
make a 2- to 3-mm deep stab incision into the linea alba. If a Veress needle is
insufflation pressure to 8 mm Hg to
used, insert it through the incision, being sure to angle the tip approximately 30°
reduce cardiovascular and pulmonary
caudal and to the right of midline to minimize risk of splenic puncture. If a Veress
needle is not available, or if preferred, a modified Hasson method can be per-
effects of pneumoperitoneum.
formed at this point, whereby the blunt trochar and cannula unit are placed into
the incision into the abdomen at the same angle recommended for Veress needle
placement. Alternatively, the catheter technique can be used. A mosquito hemo-
stat is used to insert the tip of a 5-Fr malleable catheter into the abdominal cav-
ity. Once the catheter is inserted, flush 3-mL sterile saline through the catheter to
ensure that no resistance is felt (resistance is an indication of catheter malposi-
tion). If resistance is felt, withdraw the catheter and reinsert. Once saline is

22  cliniciansbrief.com • March 2015

flushed without resistance, attach CO2 insufflation tubing to
the catheter to pressurize the peritoneal cavity to a maxi-
mum of 10–12 mm Hg. The same procedure is performed if
using a Veress needle. Subsequent to pneumoperitoneum,
remove the catheter (or Veress needle) and insert a blunt
trocar-cannula assembly or threaded screw in cannula via
the original stab incision. In some cases, minimal extension
(1–2 mm) of the incision may be needed to facilitate inser-
tion of the cannula.
Trocars should also be inserted in a caudolateral orientation
to reduce the risk of splenic injury. Insert the laparoscope
into the cannula and observe the peritoneum to ensure no
iatrogenic trauma or hemorrhage has occurred. Place a sec-
ond 5-mm instrument cannula under laparoscopic visualiza-
tion 5 cm craniad in a similar fashion to the initial port.

Correct orientation of the Veress

needle during insertion.

Image of correct port position.

STEP 3

Exploration and pancreatic biopsy. Evaluate the perito-

neal cavity by pivoting the laparoscope clockwise around
the port site. Insert the blunt probe under laparoscopic visu-
alization. The laparoscope is used to visualize and guide the
probe into the cranial abdomen.
Inspect the liver and the gall bladder to document any sec-
ondary changes from the pancreatic disease. Evaluate the
pancreas carefully, looking closely for evidence of nodules
or masses. Use the blunt probe to manipulate the duode-
num, omentum, stomach, or spleen as needed to improve
visualization of the right pancreatic limb.
If distinct lesions are noted, plan to biopsy these areas. If no
gross disease or if diffuse disease is present, plan to take 1
Isolation of the distal right limb of the pancreas.
or 2 samples from the distal tip of the right pancreatic limb.

continues

March 2015 • Clinician’s Brief 23

PROCEDURES PRO

After determining an avascular location for biopsy, insert the clamshell

biopsy forceps in place of the blunt probe.
Position the forceps to isolate the desired biopsy site, then close the for-
ceps and maintain pressure for 60–90 seconds. Gentle axial rotation of
the forceps will help release the biopsy sample from the parenchyma. A
caudal tug on the sample while keeping the forceps closed will remove
the sample. Observe the biopsy site for hemorrhage. Repeat this step as
desired for sample collection.

Author Insight A blunt probe is used to retract the duodenum, provid-

If an avascular location at the tip of the right limb cannot be ing better exposure of the pancreas.
identified, consider an open approach with biopsy of the distal
left limb.

Author Insight
The clamshell forceps can be held open and the lower jaw can be
used to gently manipulate the pancreas into position for biopsy.

Clamshell biopsy forceps ready to engage chosen

biopsy sample.

STEP 4

Control hemorrhage and close. Hemorrhage is typically

minimal, and the biopsy site should be observed for 3 min-
utes to ensure hemostasis. If minor hemorrhage occurs,
place a small piece of hemostatic foam into the biopsy
site. Evaluate all biopsy sites for hemorrhage and photo-
document hemostasis and lesions. Release residual gas
from the peritoneal cavity prior to closure. Remove all ports
and close incisions routinely. n cb

References
1. Prospective evaluation of laparoscopic pancreatic biopsies in 11
healthy cats. Cosford KL, Shmon CL, Myers SL, et al. JVIM 24:104-113,
2010. Laparoscopic image after biopsy showing adequate hemostasis at the
2. Laparoscopic diagnosis of pancreatic disease in dogs and cats. biopsy site.
Webb CB, Trott C. JVIM 22:1263-1266, 2008.
3. Evaluation of pancreatic forceps biopsy by laparoscopy in
healthy beagles. Harmoinen J, Saari S, Rinkinen M, Westermarck E.
Vet Ther 3:31-36, 2002.
4. Effect of pancreatic tissue sampling on serum pancreatic
enzyme levels in clinically healthy dogs. Cordner AP, Armstrong PJ,
Newman SJ, et al. J Vet Diagn Invest 22:702-707, 2010.

24  cliniciansbrief.com • March 2015