Extrahepatic Biliary Ductal Dilatation Research Articles

PRIMARY SCLEROSING CHOLANGITIS AND AUTOIMMUNE HEPATITIS: OVERLAPPING CHALLENGES IN DIAGNOSIS AND TREATMENT

Abstract Overlap syndromes (OS) describe the simultaneous presentation of more than one immune-mediated liver disease in a singular patient, and present unique challenges both in diagnosis and treatment. Here we report a case of primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) OS, ultimately treated with Vancomycin. A 30-year-old female with known ulcerative pancolitis (UC) and alcoholic cirrhosis in the setting of AIH presented to the ED with severe abdominal pain, bloody diarrhea, and bilious emesis. Initial labs showed ESR 48 mm/hr, CRP 32.97 mg/L, fecal calprotectin 1131.2 µg/mg, AST 45 IU/L, and total protein 9.1 g/dL. Clostridium Difficile and stool studies were negative. Patient was admitted with concern for acute UC flare. CT scan showed mild worsening of intrahepatic and extrahepatic biliary ductal dilatation suspicious for PSC, and a cirrhotic liver with signs of portal hypertension and splenomegaly (Fig. 1a). Endoscopy revealed multiple non-bleeding duodenal ulcers and grade II esophageal varices. Colonoscopy found moderately active UC Mayo score 2, worsened from prior exam. MRCP was significant for cirrhotic liver morphology with nodular surface contour, and intrahepatic and extrahepatic biliary dilatation with beading and irregularity of the intrahepatic biliary tree and cystic duct, consistent with PSC (Fig. 1b). She was diagnosed with PSC-AIH OS and underwent treatment with Prednisone, Azathioprine, and Ustekinumab with minimal improvement. Only after the addition of Vancomycin was there normalization of biochemical markers and clinical status. Autoimmune liver disease is generally categorized into hepatic (AIH) or cholestatic (PSC and PBC) predominance. PSC is known to be associated with IBD, specifically UC. It is hypothesized that PSC evolves in UC patients due to uptake into the enterohepatic circulation of proinflammatory cells from the colon; these agents typically concentrate in the biliary system where they ultimately cause the biliary ductal damage frequently seen with PSC. By targeting enteric bacteria, Vancomycin decreases the absorption of these inflammatory biliary toxins. For PSC patients with UC and co-occurring AIH, the addition of Vancomycin could significantly reduce mortality and disease burden. Several case reports and one pilot study have investigated Vancomycin’s role in the treatment of PSC. However, it remains a vastly underutilized therapy, and its role specifically in PSC-AIH OS has not been previously reported. There remains an evident need for a large double blind randomized placebo-controlled clinical trial to further support the addition of Vancomycin to the standard treatment regimen for PSC, and to establish clear parameters on effective dosage and length of treatment. In the meantime, clinicians should be aware of the possible use of Vancomycin to treat patients with PSC +/- AIH and IBD. Figure 1a: CT abdomen pelvis with IV contrast highlighting stigmata of cirrhosis with portal hypertension and splenomegaly. Image also shows worsening of intrahepatic and extrahepatic biliary ductal dilatation in the setting of PSC given the patient’s underlying history of ulcerative colitis. Figure 1b: MRCP showing beading and irregularity of the intrahepatic biliary tree and cystic duct, in keeping with known history of primary sclerosing cholangitis. This image also highlights the dilation of the intrahepatic and extrahepatic biliary system.

S3439 Lemmel Syndrome Due to Periampullary Diverticular Food Impaction

Introduction: Lemmel Syndrome is a rare cause of mechanical biliary obstruction attributed to periampullary duodenal diverticula (PAD). It was first described in 1934 as obstructive jaundice in the absence of biliary stones or malignancy. The majority of PAD are asymptomatic, however, about 5% have symptomatic disease. We present a symptomatic case. Case Description/Methods: An 80-year-old woman with history of cholecystectomy, coronary artery disease, hypertension, and diabetes was transferred from a free-standing emergency room for acute pancreatitis. She had a one day history of postprandial epigastric pain with radiation to the back. Labs on presentation included lipase above 4000 U/L, BUN 27 mg/dL, AST 316 U/L, ALT 422 U/L, ALP 292 IU/L, total bilirubin 0.6 mg/dL. Abdominal ultrasound revealed 12mm common bile duct (CBD) with intrahepatic ductal dilatation. MRCP showed intra and extrahepatic biliary ductal dilatation with dilated pancreatic duct and a 3.6 cm fluid filled periampullary diverticulum. ERCP showed a large periampullary duodenal diverticulum with food impaction causing obstruction of the ampullary orifice which was removed with forceps. Cholangiogram revealed dilation of pancreatic, common bile, and intrahepatic ducts without any filling defects. Patient improved and was discharged home. (Figure) Discussion: The incidence of duodenal diverticula is approximately 17% with PAD being the most common type. PADs are pseudo-diverticula most commonly found in the second part of the duodenum and they pose a cannulation challenge during ERCP with an increased risk of complications. PAD in the setting of biliary obstruction is known as Lemmel Syndrome. It can cause biliary obstruction by sphincter of Oddi dysfunction, direct obstruction, or via external compression by fluid or material-filled PAD. In our case, there was biliary compression due to a food-filled PAD. Cross sectional imaging is critical for diagnosis, however, ERCP is the gold standard. Several therapeutic modalities including endoscopic extraction of entrapped food or stones, extracorporeal shock wave lithotripsy, and laparoscopic diverticulectomy have been used. Our case required endoscopic extraction of diverticular food debris and adds to the limited published cases to date. Lemmel Syndrome requires a high index of suspicion when a PAD is found in the setting of biliary obstruction.Figure 1.: A. MRCP image showing a large periampullary diverticulum packed with debris. B. ERCP image of food impacted inside periampullary diverticulum. C. MRCP image demonstrating a dilated common bile duct in absence of choledocholithiasis.

S1694 IgG4-Related Sclerosing Cholangitis - An EUS Diagnosis

Introduction: Sclerosing cholangitis is a heterogenous disease associated with choledocholithiasis, biliary tumor or infection. The participation of IgG4 subclass in the pathology of sclerosing cholangitis is typically associated with autoimmune pancreatitis (60%), sialadenitis (34%), tubulo-interstitial nephritis (23%) and peri-aortitis (20%). Isolated lower duct IgG4 related sclerosing cholangitis (IgG4-Sc) is extremely uncommon and we present one such rare case. Case Description/Methods: A 73-year-old former smoker presents with complaints of yellowish discoloration of the skin and decreased appetite for a month. He has lost 44 lbs and endorses diarrhea. His family history is remarkable for lung cancer and kidney disease. Laboratory data shows cholestatic jaundice- total bilirubin of 14.2 mg/dL, AST 61 U/L, ALT 60 U/L and Alkaline phosphatase 328 U/L. CT Abdomen and Pelvis shows intra and extra-hepatic biliary ductal dilatation with common bile duct distension up to 1.4 cm. Subsequent MRCP notable for focal wall thickening involving the mid and lower portion of the common bile duct causing severe stenosis, concerning for CBD malignancy. ERCP shows proximal dilatation of the CBD with stricture of the distal end of bile duct. Biopsies obtained from the stricture were negative and tumor markers showed CEA 2.4 and CA 19-9 212. ANA screen was positive with high DsDNA antibody and elevated IgG4 at 761 mg/dL. Serum lipase was normal, anti-smooth muscle antibody and anti-mitochondrial antibody were negative. He subsequently underwent EUS/ERCP, and the CBD stricture and peri-portal lymph nodes were biopsied. Pathology from CBD stricture showed fibrosis and chronic inflammation with increased IgG4 positive plasma cells by immunohistochemistry. Hence, the patient was diagnosed with IgG4-related sclerosing cholangitis and initiated on 40 mg of Prednisone. Discussion: IgG4 related disease is a multiorgan fibro-inflammatory disease that involves infiltration of IgG4 positive plasma cells into multiple organs. IgG4-Sc is observed in elderly men who present with obstructive jaundice. HISORt criteria is used to make the diagnosis and was initially designed for diagnosis of autoimmune pancreatitis. Radiographically, Type 1 IgG4-Sc involves stenosis of only the lower bile duct and may resemble cholangiocarcinoma. Additionally, IgG4 levels may be normal further confounding the diagnostic picture. A high degree of clinical suspicion and biopsy (via EUS guidance or cholangioscopy) is imperative in making a diagnosis.Figure 1.: Endoscopic ultrasound revealing pancreatic body pseudocyst measuring 11x10 cm in diameter.

S1499 Large Pancreatic Cyst in Von Hippel-Lindau (VHL) Syndrome Causing Bile Duct Obstruction

Introduction: Von Hippel-Lindau (VHL) syndrome is a rare autosomal inherited disorder characterized by the development of multiple tumors, the most common of which is renal cell carcinoma, hemangioblastomas, pheochromocytomas, and solid and cystic tumors of the pancreas. Morbidity and mortality in VHL are more commonly related to renal and central nervous system pathologies. Extrahepatic biliary obstruction secondary to pancreatic cysts is rare in patients with VHL. We present a case of extrahepatic biliary obstruction secondary to pancreatic cysts in a patient with a history of VHL syndrome successfully managed endoscopically. Case Description/Methods: 35-year-old woman with history of VHL and course complicated by clear cell renal cell carcinoma status post partial nephrectomy, cervical/medullary/fourth ventricle hemangioblastomas status post resection, and serous cystic pancreatic adenoma status post distal pancreatectomy and splenectomy with subsequent development of insulin-dependent diabetes mellitus type 2, presented with three days of right upper quadrant abdominal pain. MR Cholangiopancreatography revealed the residual pancreas was completely replaced by multiple cystic lesions with a dominant cyst in the head of the pancreas measuring 6.2 cm causing mass effect on the portal vein and mid to distal common bile duct with resultant intrahepatic, extrahepatic biliary ductal dilatation, and gallbladder distension. Using EUS with fine-needle biopsy of the cyst was done. Intraprocedural cholangiogram during ERCP revealed 14mm dilation of proximal extrahepatic biliary duct and non-opacification of the distal extrahepatic bile duct in the region of the pancreatic head, consistent with a stricture. CBD brushings were sent for cytology and a straight plastic biliary stent was successfully deployed across the stricture. After the endoscopic procedure, the patient demonstrated clinical improvement. Discussion: The pancreatic manifestation of VHL can present as a cystic, solid, or combined lesion. The management is complex because of the challenge in the differentiation of benign cystic lesions from malignant lesions. This case highlights the fact that pancreatic involvement leading to acute biliary obstruction, although uncommon, can occur in patients with VHL syndrome. Conservative management with endoscopic biliary stent placement and endoscopic surveillance (for secondary manifestations - portal hypertension) may be helpful in these patients, however eventual surgical management may be needed.Figure 1.: (Top left) Stricture/obstruction in ERCP, (Bottom left) EUS with biopsy, (Right) MRI showing cyst, CBD, and distended gallbladder.

HIV as A Cause of Acute Liver Injury

While hepatitis is the most common infectious cause of acute liver injury, although rare, acute human immunodeficiency virus (HIV) infection should be considered in the workup for infectious causes of acute liver injury. We present a case of a 36 year old woman with no past medical history who presented to the hospital for 8 days of abdominal pain and nausea worsened with food. Labs were significant for lymphocytopenia, transaminitis, elevated alkaline phosphatase, and direct bilirubinemia. Viral hepatitis serologies were negative and imaging showed nonspecific gallbladder wall thickening, no gallbladder stones, no intra or extra-hepatic biliary ductal dilatation. No evidence of congestive heart failure. Serologies for cytomegalovirus (CMV), Epstein Barr virus (EBV), rickettsia, enterovirus, adenovirus, and parvovirus were negative. Workup for autoimmune liver disease was also negative. Liver biopsy was notable for a focus of granulomatous necrosis, suggestive of infectious or drug induced etiology. During this admission, patient was also found to have a new diagnosis of HIV with CD4 count of 235. Patient was started on bictegravir, emtricitabine, and tenofovir alafenamide with progressive improvement and eventual resolution of AST, ALT, alkaline phosphatase, and bilirubin elevation since starting anti-retroviral therapy.*++

S1547 When and Where to Look? Hepato-Biliary Malignancy in Lynch Syndrome

INTRODUCTION: Patients with Lynch Synrome have well established germline mutations in DNA mismatch repair genes that put them at higher risk for the development of multiple different types of malignancy. Risk of development of colorectal cancer is probably the most well described followed by associations with endometrial, stomach, renal pelvis, brain, skin, amongst others. Current guidelines recommend screening based on probability of these malignancies. CASE DESCRIPTION/METHODS: A 34 year old male known to carry the mutation for Lynch Syndrome was admitted with generalized fatigue. The patient reported feeling progressively worse and described associated symptoms of pruritus, dark urine and light colored stools. As part of his surveillance for Lynch Syndrome, he undergoes a colonoscopy every 2 years and an EGD every 4 years; both of which were recently normal. He otherwise has no other past medical history and takes no medications. Exam notable for normal vital signs, scleral icterus and jaundice. Labs significant for AST 112 IU/L, ALT 299 IU/L, ALP 137 IU/L, total bilirubin 8.3 mg/dL, direct bilirubin 5.4 mg/dL. A CT scan showed moderate intra and extra hepatic biliary ductal dilatation, pancreatic ductal dilatation, and an ampullary lesion. Ampullary mass seen and biopsied via ERCP, pathology showing moderately differentiated adenocarcinoma of pacnreatobiliary type. He was treated with Whipple surgery and FOLFIRINOX chemotherapy regimen. DISCUSSION: Lynch Syndrome is diagnosed in patients and families with germline mutations in DNA mismatch repair genes. This mutation puts patients at much higher risk of developing multiple types of cancer. Our case describes a patient with pancreatobiliary type adenocarcinoma of the ampulla. Small intestinal cancer is thought to affect a small population of patients with Lynch syndrome (anywhere from 0.4-12%) and society guidelines differ on appropriate screening with some recommending periodic capsule endoscopy. Routine screening for pancreatic cancer is only recommended in patients and families with Lynch syndrome who have a family member or members diagnosed with pancreatic disease. As patients with Lynch Syndrome are at risk for malignancy in virtually any location, data on less common presentations and development of noninvasive testing will be more and more valuable.

S1380 A Rare Case of Pancreatic Plasma Cell Myeloma Presenting as Obstructive Jaundice: A Case Report and Review of Literature

INTRODUCTION: Hematological malignancies affect the pancreas very rarely, with lymphomas being the most common. Pancreatic plasma cell myeloma (PCM) is exceptionally uncommon. We present a case of obstructive jaundice in a patient due to pancreatic PCM. CASE DESCRIPTION/METHODS: A 50-year old man with a history of hypertension, hyperlipidemia, and nephrolithiasis presented to the emergency department with a 3-month history of worsening mid-epigastric pain, weight loss, and jaundice. Initial laboratory workup showed low hemoglobin (11.0 g/dL), hyperbilirubinemia, and elevated protein gap. C-reactive protein and erythrocyte sedimentation rate were elevated, while vitamin B-12 and folate levels were found normal. Computed tomography revealed intra and extrahepatic biliary ductal dilatation and a hyperenhancing mass within the pancreas and porta hepatis with portal vein compression (Figure 1). Multiple enlarged retroperitoneal lymph nodes, splenomegaly, and lytic lesions in the right pubic bone were also noted. Prostate-specific antigen (PSA) and carcinoembryonic antigen (CEA) levels were normal, while CA-19-9 was found to be 191 (Normal: 0-37 U/mL). Endoscopic retrograde cholangiopancreatography (ERCP) and stenting were performed for a malignant appearing common bile duct stricture (Figure 2). Urine protein electrophoresis (UPEP) revealed a monoclonal M spike (4.7 g/dL) and gamma globulins with lambda light chains in the urine. Immunofixation confirmed the monoclonality and demonstrated IgG lambda protein. Quantitative testing showed a high level of IgG at 6.5 g/dL (Reference range: 0.7-1.6 g/dL) with decreased IgA and IgM. Biopsy of pancreatic mass and bone lesions revealed plasmacytoma with lambda light chain restriction. Bortezomib and dexamethasone were initiated with the resolution of the biliary obstruction (Figure 3). The presence of extramedullary plasmacytoma (EMP), lytic bone lesions, anemia, and monoclonal immunoglobulin production was suggestive of multiple myeloma. DISCUSSION: Pancreatic PCM typically presents with obstructive jaundice, but pancreatitis, gastrointestinal bleeding, and nausea can also occur. Pancreatic PCM offers a diagnostic challenge and should not be overlooked when evaluating hyperbilirubinemia due to obstructive jaundice if retroperitoneal lymphadenopathy and osteolytic lesions are present.Figure 1.: Arrow pointing towards pancreatic mass.Figure 2.: Arrow pointing towards common bile duct stricture.Figure 3.: Arrow pointing towards resolution of common bile duct stricture.

1338 A Rare Case of Duodenal Windsock Diverticulum; Simultaneous Biliary, and Small Bowel Obstruction

INTRODUCTION: Windsock intraluminal duodenal diverticulum (IDD) is rare congenital anomaly due to incomplete recanalization of foregut during embryogenesis. Most of the IDD are found incidentally and rarely cause symptoms. More common symptoms associated with IDD are nausea, abdominal pain and abdominal fullness. Rarely IDD can cause small bowel obstruction (SBO), pancreatitis and biliary obstruction. CASE DESCRIPTION/METHODS: This is the first reported case in literature of a windsock diverticulum causing SBO and biliary obstruction. A 44 year old man with no prior medical and surgical history presented to our hospital with acute onset abdominal pain, nausea, vomiting and inability to pass flatus or bowel movement for 3 days. Patient was clinically jaundiced and initial lab work up showed a total bilirubin level of 13.0 mg/dl. A CT abdomen and pelvis showed complete duodenal obstruction with suspected etiology of duodenal intussusception as well intra and extrahepatic biliary ductal dilatation (Figure 1). After NG decompression, patient underwent an upper endoscopy and small bowel enteroscopy with findings of a false lumen in second portion of duodenum showing focal areas of mucosal ulcerations but no intussusception was seen (Figure 2). An EUS was performed which did not show any intramural or extraluminal mass lesions. An ERCP was attempted for biliary obstruction but was unsuccessful due to lack of localization of ampulla of vater. Later during the endoscopic procedure, large amount of fresh bile flow was noted in the distal portion of duodenum. False lumen mucosal biopsies were reported negative for malignant cells. Patient's bilirubin level quickly and persistently trended down toward normal range post EGD. Clinically, his symptoms of bowel obstruction resolved completely. He underwent an upper GI series which showed contrast filling of large duodenal diverticulum which further confirmed the diagnosis of large windsock duodenal diverticulum (Figure 3). DISCUSSION: Windsock diverticulum is a true intraluminal diverticulum. In rare cases it can cause serious complications including SBO and biliary obstruction. ERCP can be challenging in case of ampullary proximity to diverticulum. Timely recognition and intervention is necessary for improved clinical outcomes. Endoscopic intervention for diagnosis and management is necessary. Endoscopic diverticulectomy can be a less invasive option for prevention of recurrence of IDD related complications especially especially in case of close proximity of ampulla to IDD.

Incidentally detected biliary ductal dilatation on contrast-enhanced CT: what is the incidence of occult obstructing malignancy?

The purpose of this study was to determine the incidence of occult obstructing malignancy in the setting of asymptomatic biliary ductal dilatation incidentally detected and without identifiable cause on contrast-enhanced CT. A retrospective search identified patients with biliary ductal dilatation on contrast-enhanced CT from March 30, 2007 to November 1, 2017. Patients with biliary symptomatology or clinical concern for an obstructing process, an explanation for biliary ductal dilatation on index CT, intrahepatic without extrahepatic biliary ductal dilatation, concurrent pancreatic ductal dilatation, and inadequate follow-up were excluded. A reference standard of at least 1year of imaging follow-up or 2years of clinical follow-up was used to exclude occult obstructing malignancy. 156 patients were included; 120 patients met imaging follow-up criteria and 36 patients met clinical follow-up criteria. No cases of occult malignancy were identified as the source of biliary ductal dilatation (95% CI 0.0-1.9%). LFTs were available for 131 patients, of which 36 were elevated (27%). One case demonstrated a 1.2-cm ampullary adenoma on endoscopic retrograde cholangiopancreatography (occult on follow-up MRI, normal LFTs at the time of the index CT). Asymptomatic biliary ductal dilatation incidentally detected and without identifiable cause on contrast-enhanced CT is likely benign in patients with normal LFTs, and further workup may not be warranted.

84-Year-Old Male With Obstructive Jaundice Due to IGG-4 Related Sclerosing Cholangitis

Patient is 83 y.o. male with history of DM type 2, hypertension, CAD, was hospitalized with 2 weeks of progressive fatigue and jaundice, bilirubin 11.2 mg/dL; ALT 227 U/L and AST 150 U/L, alkaline phosphatase 842 U/L and normal CA 19-9 U/mL. CT abdomen showed intra and extrahepatic biliary ductal dilatation with abrupt tapering of the common bile duct (CBD) at the level of the pancreatic head, prominent pancreas. ERCP revealed normal pancreatic duct and distal CBD stricture; pancreatic and biliary stents were placed, biopsies of the stricture were non diagnostic. Repeat ERCP 1 month later showed resolution of distal biliary stricture and formation of new strictures in the CBD, left hepatic duct and intrahepatic bile ducts. CA 19-9 was mildly elevated at 44 U/mL. Strictures were dilated and additional stricture biopsies were obtained. Pathology showed mild increase in numbers of IgG4 plasma cells up to 28 IgG4 positive plasma cells per 400 per high power field (HPF). Liver biopsy showed a dense peribiliary plasma cell-rich inflammatory infiltrate in a setting of fibrotic background, variable presence of eosinophils within the infiltrate, absence of prominent lymphocytic infiltration of the biliary epithelium, canalicular cholestasis without significant ductular proliferation; mild sinusoidal lymphoplasmacytic infiltrate. An immunohistochemical stain for IgG4 showed numerous peribiliary plasma cells (over 70 IgG4-expressing plasma cells per 400x microscopic field), compatible with IgG4-associated cholangitis. (Figure 1 and 2) IgG4 level was 214.2 mg/dL. Patient was started on 40 mg daily of prednisone which lead to resolution of symptoms and normalization of liver tests. Discussion: IgG4-related disease is an increasingly recognized immune-mediated condition which is comprised of a collection of disorders that share particular pathologic, serologic, and clinical features. It has slight predominance in middle age and older males as we see in our case. IgG4 — related sclerosing cholangitis ((IgG4-SC) may present as a distal or proximal-type disease with or without autoimmune pancreatitis. In some cases diagnosis may be challenging. It can mimic primary sclerosing cholangitis and cholangiocarcinoma due to elevation in CA 19-9 level. High serum immunoglobulin G4 (IgG4 level) is an important feature. Liver biopsy can aid in the prompt diagnosis. High level of suspicion and awareness of this condition can lead to prompt diagnosis and correct treatment.1251_A.tif Figure 1: No Caption available.1251_B.tif Figure 2: No Caption available.

Finding a Signet Ring in the Biliary System

65 year old female comes in with painless jaundice and weight loss of greater than 40 lbs in the past year, Patient found to have signet ring carcinoma of the stomach with metastasis to the ampulla of vater. SRCC in the ampulla of vater is a rare entity.1 While the incidence of gastric cancer is decreasing, the incidence of signet ring cell carcinoma (SRCC) is only increasing with about a 10-fold increase from 1970 to 2000.2 65 yo F with PMH of HTN, DM, non-ischemic cardiomyopathy s/p AICD 2013 (EF 45% 9/2015), CVA with expressive aphasia, cervical cancer s/p hysterectomy admitted for painless jaundice (total bili of 21) and unintentional weight loss (about 40lbs within the past year). CT abd/pelvis w/out contrast and RUQ ultrasound showed intrahepatic and extrahepatic biliary ductal dilatation (Image 1,2 and 3). EUS was significant for wall thickening in the entire body and antrum of the stomach with wall thickness measuring 14mm in the antrum and 19mm in the body; impression consistent with Linitis plastica or infiltrating gastric cancer. EUS guided FNA showed signet ring carcinoma of stomach with local metastasis to ampulla of vater. ERCP unable to be performed due to edematous mucosa; had percutaneous biliary drain placed through IR. Bili trended downward after placement of drain. She had surveillance CT chest and abdomen/pelvis w/ contrast for further staging (negative for any metastasis or lymphadenopathy). Patient was not a candidate for chemotherapy/RT/surgery. Only 26 cases previously have been described with SRCC in the ampulla of vater.1 Prognosis in early gastric cancer is better in SRCC compared to non SRCC gastric carcinomas while prognosis is less clear between SRCC and non-SRCC gastric cancers in advanced gastric cancer.2Prognosis with SRCC in the ampulla is even less clear, with >5 year survival reported in only 4/26 cases.1 Our patient was advanced gastric cancer of SRCC and given metastasis and poor functional status was not a candidate for further therapeutic measures.21365_A.tif Figure 1: No Caption available.1365_B.tif Figure 2: No Caption available.1365_C.tif Figure 3: No Caption available.

Pancreatic Head Mass: A Textbook Case

Pancreatic Cancer is one of the deadliest malignancies, accounting for over 330,000 deaths per year. Unfortunately, due to its vague symptoms, the diagnosis is often initially missed. Thus it is important to be familiar with some of the classic findings associated with this malignancy. Here we report an interesting case of a patient with a textbook presentation of pancreatic cancer. A 51-year-old male with no significant past medical history presented with dehydration, jaundice, pruritus and loose, grey bowel movements (Image 1) that began 3 weeks prior to presentation. The patient reported severe pruritus leading to scratching and extensive excoriations involving his entire body. He reported 2-3 episodes of “explosive” clay-white diarrhea daily. He denied hematochezia, melena, nausea, vomiting, unexpected weight loss, fevers, and chills. He reported drinking 4 beers a night and has a 45-pack year smoking history. On physical exam, the patient was ill appearing with moderate scleral icterus and jaundice. Initial lab work revealed elevated alkaline phosphatase, total and direct bilirubin, and lipase levels. CT abdomen and pelvis showed significant intra- and extrahepatic biliary ductal dilatation with a distended gallbladder and dilated pancreatic duct known as the “double duct sign” (Image 1). ERCP was performed and a biliary stent was placed for symptomatic relief. Biopsy from this procedure was highly suspicious for pancreatic adenocarcinoma. Given lack of metastasis, the patient underwent a pancreaticoduodenectomy to remove the mass and plans were made chemoradiation. Pancreatic adenocarcinoma is a highly morbid condition that can present with painless jaundice, pruritus, and Thomas' Sign (Image 2). Thomas' sign is the production of silver stool from combination of acholic stool and melena. This is diagnostic for pancreatic cancer that also affects the ampulla of vater. 5 year survival for patients who undergo surgery is 34.5%. Treatment options include surgical resection of the tumor, chemotherapy, radiation therapy or a combination of all of these. Given the poor prognosis in these patients, early identification of signs and symptoms such as the triad seen in this patient is important in allowing for prompt diagnosis and initiation of treatment.1306_A.tif Figure 1: No Caption available.1306_B.tif Figure 2: No Caption available.

Diffuse Large B Cell Lymphoma Presenting With Obstructive Jaundice

Diffuse Large B cell Lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin's lymphoma(NHL). Although jaundice occurs in a fair number of patients with lymphoma, it is rarely seen as a presenting complaint. We present a case of DLBCL presenting with biliary obstruction.Figure: ERCP showing dilated right, left hepatic ducts and common hepatic duct. There is narrowing of common bile duct.Figure: CT scan of the abdomen/pelvis showing a new intrahepatic and extrahepatic biliary ductal dilatation.A 62 year old male presented to the emergency room with jaundice and was found to have a total bilirubin of 13.2 and a direct bilirubin of 8.1. CT abdomen and pelvis showed new intra hepatic and extra hepatic biliary ductal dilatation, new extensive lymphadenopathy within the lower chest and upper abdomen. The patient underwent ERCP which showed a biliary stricture due to compressive lymphadenopathy. A retrievable plastic stent was placed after endoscopic balloon dilation. Patient was also noted to have extensive inguinal lymphadenopathy. A right inguinal lymph node biopsy favored a diagnosis of diffuse large B cell lymphoma. He was started only on rituximab and prednisone chemotherapy initially. After biliary stent placement, total bilirubin reduced to 4 and direct bilirubin to 1.7. Doxorubicin based chemotherapy was delayed until total bilirubin was 4, due to its excretion through bile. R-CHOP chemotherapy regimen was started at this time. A follow up PET scan in three months showed interval improvement in the lymphadenopathy and the biliary stent was removed. There is a paucity of treatment guidelines due to infrequent initial presentation of DLBCL with jaundice. Role of biliary stent placement is controversial as it provides relief of obstruction and symptoms but does not cure underlying disease. Our case highlights excellent response of DLBCL with sequencing and dosing of chemotherapeutic agents preceded by biliary drainage. Jaundice in patients with lymphoma can be due to direct hepatic/biliary involvement, extra hepatic bile duct obstructions, toxic hepatitis due to drug treatment or tumor related hemolysis. Although a rare cause of obstructive jaundice, NHL should be considered in the differential diagnosis.

Painless Jaundice Leading to Rare Entity of Signet Ring Cell Carcinoma in Ampulla of Vater

65 year old female comes in with painless jaundice and weight loss of greater than 40 lbs in the past year, Patient found to have signet ring carcinoma of the stomach with metastasis to the ampulla of vater. SRCC in the ampulla of vater is a rare entity.1 While the incidence of gastric cancer is decreasing, the incidence of signet ring cell carcinoma (SRCC) is only increasing with about a 10-fold increase from 1970 to 2000.2 65 yo F with PMH of HTN, DM, non-ischemic cardiomyopathy s/p AICD 2013 (EF 45% 9/2015), CVA with expressive aphasia, cervical cancer s/p hysterectomy admitted for painless jaundice (total bili of 21) and unintentional weight loss (about 40lbs within the past year). CT abd/pelvis w/out contrast which showed intrahepatic and extrahepatic biliary ductal dilatation. EUS was significant for wall thickening in the entire body and antrum of the stomach with wall thickness measuring 14mm in the antrum and 19mm in the body; impression consistent with Linitis plastica or infiltrating gastric cancer. EUS guided FNA showed signet ring carcinoma of stomach with local metastasis to ampulla of vater. ERCP unable to be performed due to edematous mucosa; had percutaneous biliary drain placed through IR. Bili trended downward after placement of drain. She had surveillance CT chest and abdomen/pelvis w/ contrast for further staging (negative for any metastasis or lymphadenopathy). Patient was not a candidate for chemotherapy/RT/surgery. Only 26 cases previously have been described with SRCC in the ampulla of vater.1 Prognosis in early gastric cancer is better in SRCC compared to non SRCC gastric carcinomas while prognosis is less clear between SRCC and non-SRCC gastric cancers in advanced gastric cancer.2 Prognosis with SRCC in the ampulla is even less clear, with >5 year survival reported in only 4/26 cases.1 Our patient was advanced gastric cancer of SRCC and given metastasis and poor functional status was not a candidate for further therapeutic measures.2

Painless Jaundice: A Happy Ending

Significantly elevated serum bilirubin can predict malignancy. The following case discusses a patient with a very high bilirubin and our search for its cause. A 58-year-old female presented with painless jaundice. There were no new medications, supplements or weight loss. Physical exam revealed jaundice and scleral icterus. Laboratory analysis showed a total bilirubin 40.1 mg/dL, AST 110 U/L, ALT 134 U/L and alkaline phosphatase 1665 U/L. Computed tomography revealed intra and extra-hepatic biliary ductal dilatation, tapering of the common bile duct (CBD) within the pancreatic head, and no pancreatic head mass. ERCP showed two stones in the CBD, the largest being 13.4 mm in diameter (Fig. 1, Fig. 2). Three biliary stents were placed to bypass the obstructing stones and liver tests subsequently normalized. Follow-up ERCP with cholangioscopy and electrohydraulic lithotripsy successfully removed the obstructing stones (Fig. 3) and the patient underwent cholecystectomy. Choledocholithiasis commonly presents with abdominal pain and elevated liver tests. These are often modestly elevated in a cholestatic pattern, but dramatic elevations of total bilirubin (>10 mg/dL) have been described1. Elevations of this magnitude are concerning for primary liver disease or malignancy, often leading to delays in diagnosis and extensive testing. Levels of bilirubin elevation in obstructive jaundice correlate with underlying pathology, and significant elevation (>11 mg/dL) may predict malignancy2. Painless choledocholithiasis occurs in about 24% of patients. It is more likely in patients >65 years old with diabetes mellitus, hypertension, atherosclerosis, coronary artery disease and/or cerebrovascular disease. It is associated with higher morbidity and mortality3. Multiple small (< 8mm) stones are more often found with painless presentation, whereas few (< 4) large stones (>8mm) may produce typical pain. Our patient's presentation was concerning for underlying neoplasm. Thankfully, her painless jaundice had a happy ending.Figure: ERCP showing an obstruction in the common bile duct.Figure: ERCP showing a large common bile duct stone (approximately 13.4 mm in diameter).Figure: ERCP showing free flowing contrast in the common bile duct after placement of three plastic biliary stents.

Analyzing Abnormal Liver Enzymes in a Patient With Renal Cell Carcinoma

Introduction: Targeted agents have greatly improved the prognosis of patients with advanced-stage renal cell carcinoma (RCC). However, tyrosine kinase inhibitors (TKI) may induce liver injury, which may present a challenge in diagnostic evaluation. Case Description: A 75-year-old male patient with metastatic RCC presented with new-onset nausea, decreased appetite, and jaundice, in association with abnormal liver profile testing. Metastatic sites included the ribs, thoracic vertebrae, and pancreas. He started treatment with pazopanib six weeks prior, during which liver enzymes and synthetic function tests were normal. Acetaminophen use was not significant; the patient denied the use of herbal supplements. On physical examination, he was jaundiced, and the abdomen was soft, non-tender, non-distended, without ascites or hepatosplenomegaly. He exhibited no stigmata of advanced liver disease. Labs showed ALT 484 U/L, AST 277 U/L, alkaline phosphatase 562 U/L, total bilirubin 7.9 mg/dL, direct bilirubin 6.2 mg/dL, albumin 3.3 g/dL, and INR 1.02. Abdominal ultrasound did not reveal hepatobiliary abnormalities. Abdominal MRI/MRCP did not show intrahepatic or extrahepatic biliary ductal dilatation. Laboratory testing for ANA, anti-smooth muscle antibody, anti-LKM-1 antibody, anti-mitochondrial antibody, serum ceruloplasmin, ferritin/iron profile, and viral hepatitides (A, B, and C) were unrevealing. Serum IL-6 levels were elevated. After nine days, the ALT and AST improved to 183 U/L and 186 U/L, respectively, although the total bilirubin continued to gradually increase from 7.9 g/dL to 16.1 g/dL. The patient did not develop signs or symptoms of acute liver failure. Liver biopsy showed moderate inflammatory infiltrate in portal tracts, with predominance of lymphocytes, admixed with eosinophils and neutrophils, as well as cholestasis without cirrhosis. The patient was diagnosed with pazopanib-induced hepatotoxicity, and supportive care was offered. Discussion: Pazopanib is a VEGF-receptor TKI approved for use in patients with advanced RCC. In clinical trials, incidence of hepatotoxicity was as high as 53%. Patients with a diagnosis of RCC may encounter scenarios that would require clinician interpretation of abnormal liver tests, whether as a result of therapy such as pazopanib, or a paraneoplastic syndrome of cholestasis, namely Stauffer's syndrome. Careful analysis of history and exclusion of other causes of hepatitis may allow for a more confident diagnosis.Figure: Liver biopsy: Cholestatic hepatitis with portal and lobular mixed lymphocytic and neutrophilic inflammation (H&E stain, 100X).Figure: Liver biopsy: Expansion of portal tract with inflammatory infiltrate (H&E stain, 200X).Figure: Liver biopsy: Cholestasis, mild steatosis, and inflammatory infiltrate involving the lobule (H&E stain, 200X).Table: Table. Liver enzymes and hepatic function laboratory results relative to day of pazopanib administration

Intraductal oncocytic papillary neoplasm: a benign hepatic cystic neoplasm

A 61-year-old Asian man presented with severe right upper quadrant pain which had been worsening for several months. Laboratory results indicated elevated aspartate aminotransferase and alanine aminotransferase. The subsequent ultrasound,...

Malpositioning of Biliary Stent Caused by a Very-Low-Inserted Cystic Duct: A Case Report

A 92-year-old female with history of Atrial fibrillation presented to our emergency department with the complaint of scant hemoptysis of 1-day duration. She reported a 1-week history of 4-pound unintentional weight loss, but denied fever, chills, night sweats, abdominal pain, light-colored stools or dark urine. She was found to have minimal jaundice. Laboratory workup showed total bilirubin of 7.8, alkaline phosphatase 570, ALT 364. CA19-9 was 339. A Commuted tomography scan showed a 1.8 x 1.6 cm mass arising from the head of the pancreas with intra and extrahepatic biliary ductal dilatation with double duct sign. Endoscopic Ultrasound demonstrated that the main pancreatic duct terminated in the minor papilla consistent with pancreas divisum. Fine needle aspiration (FNA) of the pancreatic mass was performed. She underwent Endoscopic Retrograde Cholangiopancreatography (ERCP) with sphincterotomy and stent placement (Figure 1). Paradoxically, her total bilirubin increased to 14.2. ERCP was repeated and it showed a stent placed in a very low-inserted cystic duct (LICD) at the level of the papilla (Figure 2). The stent was removed, and a new bare metal stent was inserted in the true common bile duct (CBD), or more accurately, the common hepatic duct (CHD). Flow is demonstrated in the biliary tree and to bypass the gallbladder (Figure 3). Total bilirubin improved to 2.6. Pathology from the FNA was suspicious for adenocarcinoma. The patient was discharged in good condition with plans for outpatient follow-up with surgery and oncology. The cystic duct's union with CHD can be abnormally proximal (near the porta hepatis or into the right hepatic duct), or distal (lower third of the CBD, intrapancreatic, or intraduodenal). ERCP is the gold standard tool for identifying anatomic variants of the biliary tree. In a recent study of patients with clinical biliary symptoms, the rate of LICD was found to be 5.4% by ERCP. An LICD, just above the level of the pancreas, causing malpositioning of a biliary stent, has been reported in the literature and is very rare. Here, we demonstrate a similar case of inadvertent placement of a biliary stent in an accessory cystic duct that joined the CHD at the level of the duodenal papilla. This case highlights the importance of verification of contrast flow into the biliary tree after stent placement. In our case, this complication occurred despite contrast flow into the biliary tree due to back flow of contrast into the true CBD.Figure 1Figure 2Figure 3

A Rare Case of Biliary Intraepithelial Neoplasia Presenting as Biliary Stricture

Introduction: Cholangiocarcinoma (CC) of the intrahepatic and extrahepatic biliary tree develops through a step-wise histopathological sequence that is preceded by premalignant neoplastic lesions. The two major precursors to invasive cholangiocarcinoma are biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB). A better understanding of the mechanism of malignant transformation of biliary epithelium into CC and early identification of precursor lesions is important in order to improve long term survival. Case: A 64 year old male presented for evaluation of jaundice and generalized malaise of three weeks duration. He reported subjective weight loss and anorexia, but denied abdominal pain or diarrhea. Physical exam was remarkable for jaundice and icterus. Lab studies were significant for elevated liver chemistry consistent with obstructive cholestasis. Tumor markers, hepatitis and autoimmune profile were normal. Abdominal ultrasound and MRCP revealed intrahepatic and extrahepatic biliary ductal dilatation, with CBD measuring 9 mm at the level of the porta hepatis with abrupt narrowing and a biliary stricture and no evidence of gallstones or choledocholithiasis. Patient underwent exploratory laparotomy with cholecystectomy, common bile duct resection, Roux-en-Y hepaticojejunostomy with jejunojejunostomy. Histopathology results showed segment of bile duct with focal low-grade dysplasia (BilIN 1), and focal acute and chronic inflammation. Discussion: BilIN refers to microscopic flat or low-papillary dysplastic lesions, often seen in association with primary sclerosing cholangitis, hepatolithiasis and choledochal cysts. BilIN is further graded based upon the degree of cellular and structural atypia: BilIN-1, BilIN-2 and BilIN-3. The natural history of BilIN, its progression to invasive CC and treatment guidelines are not fully characterized. The lesions are mostly asymptomatic, unless they enlarge to cause biliary obstruction, thus making early recognition challenging. Furthermore, radiological recognition of early precancerous lesions is not feasible, unless associated with biliary stricture, as in our case. If detected early, patient can benefit from early curative surgery.Figure 1Figure 2

A Rare Case of Oriental Cholangiohepatitis

Introduction: Oriental cholangiohepatitis is commonly seen in Asian with prevalence of < 1% in Western countries. It is thought to be secondary to parasitic infection of bile system with concomitant biliary infection that leads to production of beta-glucuronidase that play key roles in bilirubin precipitation, stone and stricture formation. Case: A 73 year-old caucasian female with history of diabetes mellitus presented with nausea, vomiting, epigastric abdominal pain, diarrhea for 1 week. Reported 70-lb weight loss over past year. CT scan was concerning for possible pancreatic mass, omental metastasis, numerous tumor nodules in mesentery and possible thrombus in portal vein. Labwork showed ALP 230, albumin 1.6, CA 19/9 45.2. US Liver showed moderate intrahepatic biliary dilation, dilated proximal common duct measuring 1.4cm. MRCP showed moderate intra and extrahepatic biliary ductal dilatation with multiple large filling defects within both intrahepatic and extrahepatic bile ducts, consistent with stones (Fig 1). EUS was done which showed normal visual exam, diffuse pancreas with mixed echogenicity. FNA of pancreatic head/body negative for malignancy. ERCP showed CBD of 1.8 cm with atleast 4 (˜1cm stones) with largest being ˜1.2cm (Fig 2). Biliary sphincterotomy was performed followed by mechanical lithotripsy, balloon extraction. A 10 Fr 9cm plastic biliary stent was placed in CBD proximal to retained stones. Repeat ERCP was done in OR with laser lithotripsy and residual stone removal in 2-3 weeks.Figure 1Figure 2Discussion: It is a serious condition owing to its intractability, frequent recurrence and predisposition of cholangiocarcinoma. Presenting symptoms include abdominal pain, jaundice, cholangitis and can lead to production of strictures and liver abscesses. US liver is first diagnostic modality as it can clearly show intrahepatic stones and biliary dilation. MRCP is the best non-invasive imaging that shows intrahepatic stones, biliary strictures and hepatic abscess. Direct cholangiography remains the gold standard with sensitivity of almost 100% in the detection of obstruction. The goals of treatment include treating cholangitis (fluids/antibiotics), preventing recurrence, clearance of stones, correction of strictures, restoration of biliary drainage and to stop the progression of the disease. There is no definitive treatment owing to the complicated nature of the disease. Urgent endoscopic biliary decompression prevents patient from going into shock. Hepatic resection has shown to reduce the risk of recurrence of stones, since it removes not only intrahepatic stones but also the associated pathological bile ducts damaged by strictures. Liver transplantation is usually the only treatment option in cases of diffuse liver parenchyma involvement and development of cirrhosis.Table 1: Grading the severity of hepatolithiasis