Gastroenterology Grand Rounds - Baylor College of Medicine

Gastroenterology Grand Rounds - Baylor College of Medicine

Gastroenterology Grand Rounds January 22, 2015 Fellow: David Tang, M.D. Faculty: Kal Patel, M.D. Case Presentation 65 year old woman Presented to Houston area hospital in Sept 2013 with nausea, anorexia, and weight loss x

2 months Jaundice x 1 week Denied abdominal pain Abdominal ultrasound showed intrahepatic biliary dilation CT Sept 2013 Case Presentation AST

111 ALT 125 Alk Phos 341

Total Bilirubin 18.2 Direct Bilirubin 14.7 Total Protein

6.9 Albumin 2.9 CEA 1.39

CA 19-9 < 1.00 ERCP Sept 2013 Case Presentation Brush cytology Unsatisfactory for evaluation

FNA cytology Suspicious ERCP Nov 2013 Case Presentation Brush cytology Negative (scant cellularity and poor preservation)

Intraductal biopsy No tissue identified FNA cytology Indeterminate (scant cellularity) Case Presentation Diagnostic laparoscopy December 2013 Cystic duct densely adherent to duodenum and porta hepatis with significant inflammation. No

discrete mass was seen. Patient then offered extended right hepatectomy for presumed malignancy. Case Presentation Patient underwent portal venous embolization to optimize future liver remnant. But after further consideration, patient decided against hepatectomy.

She was hospitalized in August 2014 with nausea and vomiting. EGD August 2014 Case Presentation Duodenal biopsy Intestinal type mucosa with chronic inflammation Duodenal stent was then placed

EUS with FNA was then repeated Courtesy of Dr. Zarrin-Khameh, Pathology Courtesy of Dr. Zarrin-Khameh, Pathology Diagnosis Perihilar Cholangiocarcinoma (pCCA)

Clinical Questions Do advanced cytologic techniques improve diagnostic accuracy over brush cytology and transpapillary biopsy of pCCA? What are the options for tissue diagnosis of pCCA beyond brush cytology and transpapillary biopsies? How should these diagnostic modalities be integrated in the diagnosis of RFA?

Classification of CCA Intrahepatic CCA Perihilar CCA Extrahepatic CCA Distal CCA Incidence of Extrahepatic CCA Review of SEER registry from 1992 2007 However, before 1992, pCCA was not given

unique ICD-O code. Between 1992 and 2000 pCCA was only able to be linked to iCCA Tyson Dig Dis Sci 2014 The Problem with Tissue Diagnosis Rizvi Gastro 2013 The Problem with Tissue Diagnosis

Hattori BJS 2011 The Problem with Tissue Diagnosis Sensitivity Specificity Brush Cytology

23 - 100% 100% Transpapillary Biopsy 52 83% 100%

Diagnostic uncertainty leads to delay in definitive treatment and repeated procedures are costly. We should be familiar with our arsenal of diagnostic tools, including when and how to deploy them Tamada World J Gastroenterol 2011 Advanced Cytologic Techniques Fluorescence in situ Hybridization (FISH)

Diploid Trisomy Polysomy Moreno Gastro 2006 Advanced Cytologic Techniques Digitized Image Analysis (DIA)

Levy Am J Gastroenterol 2008 Advanced Cytologic Techniques 33 patients with biliary strictures underwent brush cytology, DIA, and FISH Reference standard surgical specimen or at least 9 months of follow up Moreno Gastro 2006

Advanced Cytologic Techniques 284 patients with biliary strictures underwent brush cytology, DIA, and FISH Reference standard surgical specimen or at least 6 months of follow up Cytology 1 malignant only Cytology 2 malignant + suspicious Cytology 3 malignant + suspicious + atypical FISH 1 polysomy

FISH 2 polysomy + trisomy 7 Barr Fritcher Am J Clin Pathol 2007 Single Operator Cholangioscopy (SOC) Victor World J Gastroenterol 2011 Single Operator Cholangioscopy (SOC) Study of 42 patients with biliary strictures who

underwent SpyGlass with SpyBite Reference standard surgical specimen or clinical follow up 18 patients with CCA SpyBite Sensitivity Specificity 88%

94% Manta Surg Endosc 2013 Single Operator Cholangioscopy (SOC) SpyBite biopsies in 33 patients with biliary stricture and previously

inconclusive brush cytology and/or biopsy histology Ramchandani GIE 2011 Endoscopic Ultrasound with Fine Needle Aspiration (EUS with FNA) Endoscopic Ultrasound with Fine Needle Aspiration (EUS with FNA)

74 patients with extrahepatic CCA who underwent EUS with FNA Reference standard surgical specimen or unequivocal malignancy on cytology or clinical course Overall Sensitivity 79% EUS with FNA

Sensitivity in proximal CCA 59% Sensitivity in distal CCA 81% Mohamadnejad GIE 2011 Endoscopic Ultrasound

44 patients with potentially resectable hilar masses suspicious for pCCA with previous negative brush cytology and/or histology Reference standard surgical specimen or clinical course EUS with FNA Sensitivity Specificity

PPV NPV 83% 100% 100%

57% Fritscher-Ravens Am J Gastroenterol 2004 EUS with FNA and Risk of Tumor Seeding Incidence of tumor seeding is difficult to assess: Tumor seeding may deposit cells that are undetected in the surgical specimen or deposited outside of field of resection

Inability to differentiate between tumor recurrence versus tumor seeding Levy Curr Opin Gastroenterol 2012 EUS with FNA and Risk of Tumor Seeding 191 patients with unresectable pCCA enrolled for neoadjuvent chemotherapy and radiation before liver transplant.

16 patients had trans-peritoneal FNA before neoadjuvent therapy All patients had staging laparotomy after neoadjuvent therapy Prevalence of metastasis on laparotomy staging Trans-peritoneal FNA No FNA 6/16 (37.5%)

14/175 ( 8%) Heimbach HPB 2011 Intraductal Ultrasound (IDUS) Malignant Heterogeneous echo poor lesions with irregular margins

Benign Homogeneous echo rich lesions with smooth margins Domagk Gut 2002 Intraductal Ultrasound (IDUS) Prospective study of 60 patients with biliary strictures undergoing IDUS Reference standard surgical specimen

Domagk Gut 2002 Proposed Strategy for Tissue Diagnosis Brush cytology + FISH or DIA and/or Intraductal Biopsy Non-resectable Resectable

Cholangioscopic Biopsy MRCP + CA 19-9 Surgical Specimen EUS FNA

IDUS Summary Brush cytology may suffer from low diagnostic yield due to scant tumor cellularity and desmoplasia. Advanced cytologic techniques (DIA and FISH) improve on cytology sensitivity. Cholangioscopic biospies may be an option after negative brush cytology or transpapillary biopsy.

EUS with FNA results in improved sensitivity but suffer from risk of tumor seeding. IDUS may be sensitive but cannot sample tissue Follow Up Tumor board decision for chemotherapy follow by radiation. Seen in Surgical Oncology clinic and deemed not a candidate for resection due to poor nutritional status and morbidity of

hepatectomy and Whipple. EGD September 2014 EGD September 2014 Treatment of pCCA Lobar hepatic resection with regional lymphadenectomy and hepaticojejunostomy Neoadjuvant chemoradiation followed by liver

transplant Tumor less than 3 cm in diameter No metastasis Unresectability Systemic chemotherapy Razumilava Clin Gastro Hepatol 2013 Photodynamic Therapy (PDT) Photosensitizer is administered via IV and

accumulates preferentially in tumor tissue Tumor is exposed to light of a certain wavelength which activates photosensitizer resulting in damage to tumor tissue Depth of necrosis is between 4 to 6 mm Major side effect of systemic photosensitivity Ortner Best Pract Res Clin Gastroenterol 2004 Photodynamic Therapy (PDT) Randomized controlled trial between 31 patients with

unresectable CCA randomized to stenting alone vs stenting + PDT. Median survival time was 493 days in stenting + PDT group compared with 98 days in stenting only group (p < 0.0001). Ortner Gastro 2003

Intraductal Radiofrequency Ablation Dolak Surg Endosc 2013 Intraductal Radiofrequency Ablation 58 patients treated with intraductal RFA over two years. Overall, median survival was 10.6 months from the time of the first RFA and 17.9 months from the time of initial diagnosis. The median stent patency after the last electively

performed RFA was 170 days and was almost significantly different between metal and plastic stenting (218 vs. 115 days; p = 0.051) One major complication of partial liver infarction thought to be thermal injury of a hepatic artery Dolak Surg Endosc 2013 FISH and DIA in Negative Cytology and Histology

Levy Am J Gastroenterol 2008 Courtesy of Dr. Zarrin-Khameh, Pathology

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