bluuebunny/crossref_metadata_2025 huggingface dataset:
2297 Tyrosine Kinase Inhibitor-Induced Hepatotoxicity: A Case Series
Authors: Khurana Shruti , Herman Andrew , Dedania Bhavtosh , Younes Mamoun , Machicao Victor
Published: October 2019

INTRODUCTION:

Tyrosine kinase inhibitor (TKI) is indicated for the treatment of multiple cancers. Known side effects include vomiting, myalgia, skin rash, bone marrow suppression and mild hepatotoxicity. We report two cases of TKI-mediated hepatotoxicity with variable outcomes in patients with no prior history of chronic liver disease (CLD).

CASE DESCRIPTION/METHODS:

CASE 1: A 66-year-old Caucasian woman developed maculopapular rash, fatigue, low-grade fevers, neutropenia and significant transaminemia (hepatocellular injury) a month after initiation of Imatinib for GIST (Table 1). Workup for alternative explanation of abnormal liver function test (LFT) including autoimmune markers were unremarkable and TKI was discontinued due to presumed hepatotoxicity. A liver biopsy was performed showing features of drug-induced liver injury (DILI) with patchy perivenular, focal bridging, necrosis, mild cholestasis, portal and mild periportal fibrosis. Her LFTs worsened despite a trial of prednisone. Six months later, a repeat liver biopsy and imaging showed cirrhotic changes (Figure 1). CASE 2: A 85-year-old Hispanic woman with metastatic renal cell carcinoma was started on TKI complained of fatigue and new onset jaundice (Table 2). After a negative work-up for her abnormal LFTs, a liver biopsy was performed which showed changes consistent with drug-related hepatitis (Figure 2). Hence, systemic steroids were started with a gradual normalization of LFTs without any cirrhotic changes on imaging.

DISCUSSION:

Hepatotoxicity is a known side effect of Imatinib generally manifesting as hepatocellular injury in as many as 2.7% of patients. Cases have ranged from mild elevation in transaminases to progressive irreversible cirrhosis, which has resulted in death. Histologic features of TKI-induced hepatotoxicity include inflammation, fatty degeneration, and liver necrosis. Most hepatotoxicity improves after discontinuation of the drug with limited date on use of systemic steroids. However, cirrhosis due to TKI in-spite of drug discontinuation and treatment with prednisone is not common. Since there are no guidelines on treatment, oral steroids should be considered, apart from periodic monitoring of LFTs for patients on TKI. Infrequently, orthotopic liver transplantation in patients with decompensated cirrhosis is required. We present two cases of TKI mediated hepatocellular injury with different overall outcomes in spite of similar treatment protocol suggests different mechanisms for DILI.
2298 Novel Use of N-Acetylcysteine in the Management of Immunotherapy-Induced Acute Liver Injury
Authors: Patel Tarang , Hudhud Dania , Tarun Tushar , Krvavac Armin
Published: October 2019

INTRODUCTION:

There is limited research regarding the use of N-Acetylcysteine (NAC) to manage non-acetaminophen induced acute liver failure (NAI-ALF). NAC has an anti-inflammatory, antioxidant effect, and improves oxygenation by vasodilating microcirculation. A mortality benefit and association with lower hospitalization length has been seen when using NAC in NAI-ALF. Use of immunotherapy to treat cancer has recently increased, and acute liver injury has been reported with many agents. This case examines using NAC to manage immunotherapy induced acute liver injury (ITI-ALI).

CASE DESCRIPTION/METHODS:

Patient is a 67-year-old Caucasian female with a medical history of hyperlipidemia and well-differentiated angiosarcoma of the right breast, diagnosed in 2011. She had mastectomy and adjuvant chemo-radiotherapy resulting in remission. Surveillance abdominal CT, in 2017 showed new enhancing hepatic lesions. Abdominal MRI confirmed these concerning lesions. A cervical mass was noted, which was biopsied, and diagnostic of metastatic angiosarcoma. She was started on Pazopanib. Two weeks into therapy, she experienced darkened urine, myalgia, and abdominal pain. Labs just prior to admission showed transamninits, ALT of 522 units/L and AST of 456 units/L. Admission labs showed worsening transaminitis, ALT 1377 units/L and AST 1212 units/L. Exam showed jaundice and diffuse abdominal pain. Acetaminophen levels were undetectable. Abdominal ultrasound showed patent hepatic vasculature, normal liver size, appearance, echogenicity, and no intrahepatic ductal dilation or masses. Additionally, serologies for herpes simplex virus, Ebstein Barr virus, cytomegalovirus, viral hepatitis, anti-nuclear antibody, and anti-smooth muscle antibody were negative. Ultimately, her acute liver injury was suspected to be ITI-ALI. NAC was started and Pazopanib was held. Hepatic function was serially monitored, and her acute liver injury rapidly improved. She was discharged and repeat labs on follow-up continued showing improvement in transaminases (Figure 1).

DISCUSSION:

The use of NAC in NAI-ALF was described in a prospective study by Mumtaz, Azam, et al, and in a randomized, case-control trial by Nabi, et al. Neither studies had patients who had developed ITI-ALI. Both studies were able to conclude that using NAC in NAI-ALF reduced mortality and hospitalization length. Further prospective studies should be conducted to identify if there is a statistically significant effect on mortality and length of hospitalization by using of NAC in ITI-ALI.
2326 Primary Squamous Cell Carcinoma of the Liver: A Rarity
Authors: Mago Sheena , Rawi Sarah , Ramlal Bharat
Published: October 2019

INTRODUCTION:

Primary liver squamous cell carcinoma (PLSCC) is a very rare entity with less than 40 reported cases since 1970. PLSCC has been known for late diagnosis, high malignancy rate, and poor prognosis of less than 1 year. The exact pathogenesis of PLSCC is unclear, though various theories exist.

CASE DESCRIPTION/METHODS:

A 72-year-old male with a history of NASH cirrhosis and hepatocellular carcinoma (HCC) status post right hepatic lobectomy 11 years prior and microwave ablation of a presumed recurrent HCC mass just 5 months prior, presented with a 2-month history of progressive fatigue, shortness of breath, lower extremity edema, and abdominal pain. He was hypotensive with an initial blood pressure of 90/54mmHg and had a distended abdomen without evidence of jaundice, encephalopathy, or acholic stools. Labs were notable for WBC 16.9 × 10^3/uL, lactic acid of 4.5mmol/L, and alpha-fetoprotein marker of 1.9ng/mL. CT Abdominal/Pelvis revealed a large burden of diffuse intrahepatic lesions spanning all lobes—findings compatible with HCC—and multiple bilateral kidney simple cysts. Patient underwent an ultrasound guided biopsy of the largest hepatic lesion measuring 2.3 × 2.0 × 2.8 cm. Unfortunately, his condition rapidly worsened with significant elevation in liver enzymes and lactic acid and he passed away. Pathology results resulted shortly after his passing and showed a partially necrotic high grade carcinoma favoring squamous cell carcinoma. It was strongly positive for immunomarkers: CK5, CK7, p40, HSP70 (non-specific), but negative for GATA3, CK20, glypican 3, Hep Par1, S100 protein.

DISCUSSION:

In this case, the patient was thought to have HCC, but its aggressive clinical course was highly unexpected. Data on the diagnosis of PLSCC is limited and the mechanism is uncertain, though it has a strong association with hepatic cysts, stones, and cirrhosis. Hepatic cysts were not clearly visualized on imaging, though studies do show a positive correlation between the incidence of kidney and hepatic cysts. As this patient had multiple benign bilateral kidney cysts, we suspect that hepatic cysts could have also been present which makes PLSCC very likely given the lack of evidence of a different primary source. A liver carcinoma with such an aggressive clinical course should increase clinical suspicion for PLSCC, however further understanding of the pathogenesis of this disease needs to be investigated.
2327 Not Just a Cyst: Rare Presentation of LUQ Pain
Authors: Henriquez Richard , Comba Isin Y. , Kumar Sundeep , Bashir Khawaja , Wallis-Crespo Maria , Qazi Omar , Bhatia Lakhinder
Published: October 2019

INTRODUCTION:

Lymphangioma is a benign congenital malformation of the lymphatic system that is relatively common in juvenile population. Rarely, it can be seen in adults and majority of the cases are reported in the head and neck region (70-75%). Typically, these malformations are asymptomatic. In this report, we present a rare case of splenic lymphangioma presenting with severe, intractable abdominal pain.

CASE DESCRIPTION/METHODS:

A 50-year-old female presented with three-month history of progressive abdominal pain located below the left subcostal margin. Initial vital signs and lab work were unremarkable. Physical exam was significant for tenderness in the left upper abdominal quadrant. Computed tomography (CT) scan of abdomen with contrast revealed a hypointense lesion measuring up to 1.8 cm in the posterior aspect of the spleen. Subsequently, a hypo-enhancing splenic mass in the corresponding location was demonstrated in T1-weighted MRI images (Image 1A). The spleen was normal-sized and there were no liver lesions. A total splenectomy was performed with resolution of the pain during the hospitalization. Histopathological examination of the lesion revealed multiple cystic cavities containing pale eosinophilic fluid (Image 1B) resembling lymph, consistent with splenic lymphangioma. The cystic cavities were lined with elongated cells with bland nuclei and scant cytoplasm (Image 1C). Immunohistochemically, the lesion stained positive with CD31 (Image 1D).

DISCUSSION:

Clinical presentation of splenic lymphangioma varies depending on the spleen size with majority of the patients being asymptomatic. The diagnosis is usually made incidentally on routine imaging studies. Based on the clinical data and imaging results, our differential diagnosis included hemangioma, complex splenic cyst, lymphangioma, lymphoma, and pseudocysts. The splenic lymphangioma was diagnosed on microscopic examination following a splenectomy which was done to avoid any further complications such as; infection, rupture, hemorrhage and pleural effusions. The treatment modality of choice was complete surgical resection in this patient given relevant history. Other therapeutic modalities such as aspiration or drainage have not shown effective results in the literature. Despite the rarity, early recognition of these lesions is important as the delay in surgical intervention can result in complications.
2357 Drug-Induced Liver Injury (DILI) Does Not Always Follow the Textbook
Authors: Ajayi Teminioluwa A. , Dawodu Ejemenare A. , Huh Won J. , Scanga Andrew E. , Izzy Manhal
Published: October 2019

INTRODUCTION:

Drug-induced liver injury (DILI) is a leading cause of acute liver injury in the US, most commonly caused by antibiotics and NSAIDS. The clinical history and biochemical pattern are often the most important clues to the diagnosis and a classic pattern can save the patient an invasive procedure such as liver biopsy. It becomes diagnostically challenging when the biochemical presentation is inconsistent with the drug reported, such as in this case.

CASE DESCRIPTION/METHODS:

A 34-year old Caucasian man presented to the hospital with progressive jaundice, vomiting and malaise. Medical history is remarkable for Ankylosing Spondylitis (AS) for which he is on Secukinumab, and for acute sinusitis diagnosed 23 days prior in clinic for which he completed a 10-day course Amoxicillin-Clavulanate (AC). Liver tests from 15 months prior were normal. Liver tests on presentation were remarkable for total bilirubin of 4.5 mg/dL, AST of 163 U/L, ALT of 449 U/L, and ALP of 132 U/L and peaked at total bilirubin of 12.5mg/dL, AST of 702 U/L, ALT of 1,292 U/L and ALP of 184 U/L. Viral hepatitis panel was notable for Hepatitis A and B immunity and Hepatitis C IgG positive but with undetectable viral load. Autoimmune hepatitis markers were also normal. In view of the progressive uptrend in transaminases despite medication discontinuation, hepatocellular biochemical pattern, and history of autoimmune disease (i.e., AS), autoimmune hepatitis was suspected and a liver biopsy was done. Liver biopsy was notable for mild mixed portal inflammation and bile duct distortion. The overall impression was DILI. He resumed Secukinumab but not AC. Upon follow up one month later, his liver tests completely normalized.

DISCUSSION:

AC-DILI presents most frequently among elderly men with a cholestatic biochemical pattern and self-limited course. AC-DILI of hepatocellular pattern is rare in adult patients, although more common among pediatric patients. Our report, interestingly, describes a distinct hepatocellular biochemical pattern of AC-DILI in an adult male patient with an underlying autoimmune disease. HLA B-27 allele (class I) is a strong genetic risk factor for the development of AS. Studies have shown that predisposition to AC-DILI is influenced by certain HLA haplotypes perhaps suggesting an involvement of the adaptive immune system. However, further studies are needed to determine whether this association might increase risk for organ injury as in DILI or if it alters the pattern of presentation and expected clinical course.
2368 A Rare Case of Segmental Arterial Mediolysis in a Patient With Alpha-1 Antitrypsin Deficiency and Alcoholic Cirrhosis
Authors: Alimirah Maryam , Selim Ranya , Venkat Deepak
Published: October 2019

INTRODUCTION:

Alpha-1 antitrypsin deficiency (AAT deficiency) is a systemic disease characterized by lack of the protease inhibitor, alpha-1 antitrypsin and typically manifests as severe emphysema and/or liver disease. There are several case reports describing vascular compromise in patients with AAT deficiency, however mostly in the context of systemic vasculitis and connective tissue disease. Segemental arterial medioloysis (SAM) is a rare non-vasculitis, non-atherosclerotic arteriopathy of middle and small arteries that can lead to aneurysmal dilation or arterial stenosis. We report the first case of a patient with cirrhosis secondary to AAT deficiency noted to have arteriopathy due to SAM.

CASE DESCRIPTION/METHODS:

A 30 year old patient with end stage renal disease (ESRD) on hemodialysis, alcoholic cirrhosis and underlying AAT deficiency presented to our tertiary care center for liver transplant evaluation with a presenting MELD score of 39. Evaluation for other causes of cirrhosis revealed AAT deficiency with a homozygous ZZ phenotype and undetectable serum levels. As part of his pre-transplantation workup at our institution, he underwent computed tomography angiography (CTA) of the abdomen and pelvis which revealed severe irregular narrowing of the celiac axis. Similar narrowing was noted of the renal arteries and splenic artery and focal aneurysmal dilation of the hepatic and gastroduodenal arteries was additionally seen (Image 1). Autoimmune serologies were negative. Patient proceeded to orthotropic liver transplantation during his hospitalization. Intraoperatively, hepatic artery appeared visually vasculitic but histopathologic report was consistent with diagnosis of SAM. Due to concern for potential graft compromise that could result from the recipient hepatic artery aneurysm, an aortic conduit was performed using the donor vessels with anastomosis to the recipient supraceliac aorta.

DISCUSSION:

To our knowledge, there is only one other published report describing SAM in a patient with co-existing AAT deficiency. SAM in this case resulted in hepatic aneurysm which complicated liver transplantation, necessitating alternative graft revascularization via an aortic conduit. Although doppler evaluation 3 days after transplantation showed hepatic artery anastomosis was still patent, the rate of complications related to aorto-hepatic bypass grafts is high, and close follow up remains prudent.
2413 Another Downside for Depression: A Case of SNRI-Induced Liver Injury
Authors: Odah Tarek , Sun Lishi , Treadwell Thomas
Published: October 2019

INTRODUCTION:

Antidepressants are one of the most prescribed medications in the United States with duloxetine being reported as one of the top fifty drug prescriptions. Self-limited liver test abnormalities have been reported with duloxetine use but only a few case reports describe clinically apparent hepatitis following duloxetine use.

CASE DESCRIPTION/METHODS:

A 35-year-old African American woman with a past medical history of depression presented with few days of worsening upper abdominal pain, nausea and multiple episodes of non-bloody emesis. Initial laboratory tests revealed liver test abnormalities with ALT of 1176 U/L, AST of 596 U/L, bilirubin of 1.6 mg/dL (but with normal ALP) and INR of 1.65. Full workup including viral hepatitis, EBV, CMV, drug toxicology screen (including acetaminophen), lipase, and ceruloplasmin among others turned out to be negative. Autoimmune hepatitis markers were negative other than mild elevation of anti-smooth muscle antibody at 33 units (normal < 19). Abdominal ultrasound with Doppler showed no abnormalities without any evidence of biliary obstruction. The patient denied any alcohol or illicit drug use. Patient endorsed having a recent contact with a sick squirrel so leptospira IgM was ordered which was non-reactive. The patient denied taking any medications other than duloxetine which she was started on within the last two months but she stopped taking it when she started to vomit a few days before presentation. In the second day of hospitalization, patient's LFTs peaked with ALT above 7000 U/L and AST of 5409 U/L but it then started to decrease in the following days with normalization of her bilirubin and INR as well as improvement of her symptoms with supportive care. No corticosteroids or antibiotics were given. Patient's clinical presentation with the timeline of her duloxetine use and laboratory finding indicate that duloxetine was the likely cause of her acute hepatitis.

DISCUSSION:

Few cases described clinically evident hepatotoxicity following duloxetine treatment. Most duloxetine-induced hepatotoxicity was seen in females with symptoms starting in the first few months following initiation of duloxetine. Typically there was an elevation of ALT > AST and with some cases having bilirubin elevation as well as elevation of one of the autoimmune hepatitis markers in some cases. Clinicians should be vigilant toward possible hepatotoxicity following initiation of antidepressant even in patients with no pre-existing chronic liver disease or alcohol abuse history.
2419 Fatal Outcome Associated With Herbal Supplements
Authors: Ahmad Minhaz , Chowdhury Nazif , Saleem Atif
Published: October 2019

INTRODUCTION:

Herbal and dietary supplements are widely used without prescription and used by the public as harmless remedies for a variety of ailments. It is difficult to determine causal relationships between herbal preparations and hepatotoxicity. We present a case of fulminant hepatic failure from over-the-counter hair regrowth supplements containing Polygonum multiflorum.

CASE DESCRIPTION/METHODS:

A 71-year-old male presented to the ER with complaints of abdominal discomfort and jaundice, associated with nausea and vomiting. He went to the ER ten days prior for abdominal discomfort and nausea, labs showed total bilirubin 1.8, ALP 141, AST 267, ALT 85, platelet 70, BUN 31 and Creatinine 1.2. CT abdomen showed duodenitis and was discharged with Metoclopramide. His symptoms continued to worsen. 12 weeks prior, he started a hair regrowth supplement which contained Polygonum multiflorum. Pertinent labs were-Total Bilirubin 9.8, AP 280, AST 445, ALT 156, platelet 49, BUN 85, creatinine 3.4 and INR 1.82. CT abdomen showed mild hepatic steatosis, mild peripancreatic and periduodenal inflammatory changes. Ultrasound of the gallbladder showed no gallstones or cholecystitis. Normal CBD and common hepatic duct. Hepatitis A, B, C, Anti-smooth muscle antibodies, anti-mitochondrial antibodies, smear for parasites and tick borne were negative, IgG, IgM, IgA – normal, Ceruloplasmin 45. Acetaminophen level <10. He was getting supportive treatment. Day 3 labs showed AST 556, ALT 151, AP 278, total bilirubin 15.1, direct bilirubin 14.6, PT 23.7, INR 2.03. platelets 24, BUN 97, creatinine 2.5. He was started on Acetylcysteine and Lactulose, then transferred to a hospital with a liver transplant facility, where toxicology screening was positive for P multiflorum. He was not a candidate for liver transplant and labs continued to worsen. Shortly thereafter he coded while getting an HD catheter for dialysis and expired. Liver biopsy after autopsy showed diffuse necrosis of hepatic cells.

DISCUSSION:

The mechanism of hepatotoxicity of P multiflorum is unknown but it is known to have anthraquinones including chrysophanol, emodin, and rhein which can induce hepatotoxicity. The pattern of enzyme elevations is typically hepatocellular or mixed and the clinically resembles acute viral hepatitis. The latency to onset ranges from a few days to as long as 6 months. Liver biopsies show changes typical of acute hepatitis. The course is usually self-limited but there are also a small number of patients with liver failure and even death.
2439 Cystic Fibrosis Liver Disease: A Curious Case of Atypical Cystic Fibrosis Diagnosed in Adulthood
Authors: Harriss Patrick B. , Jogimahanti Anusha , Herlevic Vincent , Samant Hrishikesh , Morris James D. , Jordan Paul
Published: October 2019

INTRODUCTION:

Cystic fibrosis (CF) poses considerable morbidity and mortality. Largely identified in children with “typical” pulmonary problems, some present past adolescence and instead display “atypical” complaints. CF liver disease (CFLD) has a significant disease burden as a leading cause of death in CF. Symptom variation makes diagnosing CF in adults difficult. Our case report describes a diagnosis of atypical CF and CFLD in adulthood after nearly two decades of inconclusive findings. The case highlights hepatic sequelae of CF, disease diversity, and the impact of delayed diagnosis.

CASE DESCRIPTION/METHODS:

We present a 32-year-old African American female first noted to have elevated liver function tests (LFTs) on routine labs at age 16, yet was asymptomatic. Despite numerous clinical encounters over 17 years - including chemistry panels, imaging, and biopsies - the etiology remained unclear. In adulthood, she began experiencing chronic abdominal pain, and was later found to have critically low magnesium levels resulting in a seizure. The differential was expanded, and sweat chloride testing was positive, though genetic testing was negative. Given clinical history of high LFTs with abdominal pain and hypomagnesemia, appearance of symptoms past age 18, and unfixed results, she qualified for the diagnosis of atypical CF with CFLD. Her delayed diagnosis was further masked by unconventional misnomers not typically seen in CF. The patient was enlisted by our CF team for treatment and surveillance, and her LFTs improved.

DISCUSSION:

Our patient's clinical course made the diagnosis of CF less obvious, including: age, race, lack of family history, absence of pulmonary complications, presence of fertility, and vagueness of complaints. While sweat chloride testing was positive, genetic testing was negative. Retrospectively, each result lends itself to the diagnosis of atypical CF, which may show negative genetics despite sweat testing. The presence of a positive sweat test and clinical history is consistent with non-classic CF, and the chronically elevated LFTs and abdominal complaints were indicative of CFLD. Formal declaration of CFLD is important, as it leads to biliary cirrhosis and portal HTN, imposing high mortality. No gold standard modality exists for CFLD, further making diagnosis difficult in lieu of typical CF features. Our case emphasizes the importance of identifying both atypical CF and CFDL, how limited findings confound diagnosis, and the role of a multi-disciplinary team approach for CF patients.
2468 Humeral Fracture as the Only Presenting Symptom of a Metastatic Intra-Hepatic Cholangiocarcinoma: A Rare Cancer With Rare Presentation
Authors: Mehmood Asif , Ullah Waqas , Iqbal Umair , Patel Pranav , Essrani Rajesh
Published: October 2019

INTRODUCTION:

Cholangiocarcinoma (CCA) is a malignant tumor which originates from the epithelial cells of bile ducts. Abdominal pain and jaundice are the most common presenting symptoms. It commonly metastasizes through lymphatics to regional lymph nodes, followed by involvement of liver, lungs and peritoneum via blood. Bone metastasis is very rare although it has been reported. We are presenting an unusual case with initial presentation of appendicular bony metastatic disease without any GI symptoms.

CASE DESCRIPTION/METHODS:

59-year-old non-smoker male with past medical history of obstructive sleep apnea initially presented to ER with right arm pain while standing from a chair and felt crack in his arm. Physical exam was unremarkable except right mid arm mild swelling and tenderness. Right arm x-ray showed an acute comminuted fracture of proximal humeral shaft with minimal displacement. A CT scan was obtained due to the low energy nature of this injury to rule out pathologic etiology, but this was negative. Blood work up was positive only for normocytic anemia with hemoglobin of 10 g/dl. He was placed in a sling and scheduled to follow-up with orthopedics as outpatient. Four weeks follow up x-ray showed persistent fracture and prominent bone resorption concerning for its pathological nature. Patient was referred to oncologist. Patient remained asymptomatic except right arm pain and some swelling. Extensive work up was initiated. Laboratory investigation showed elevated LFTs with cholestatic pattern. CT CAP with contrast showed significant metastatic abdominal lymphadenopathy, ill-defined mass in the right lobe of the liver and splenomegaly. A bone scan showed uptake in the right mid humerus but no additional findings. Patient underwent CT guided bone biopsy which was consistent with metastatic intrahepatic CCA. Given aggressive growth in short duration and refractory pain, intralesional debulking and metallic end prosthetic segmental reconstruction of the right humeral diaphysis was performed followed by radiation therapy. Oncology recommended to start chemotherapy although prognosis is grim.

DISCUSSION:

CCA is an aggressive tumor with poor prognosis. The pattern of metastasis is usually through lymphatics and further spread via hematogenous route. Appendicular bone metastasis is very rare phenomena and only few cases reported so far. Physicians should have low threshold to investigate low energy injuries leading to bone fractures, in depth for pathological fractures and possibly underlying malignancy.
2481 Severe Transaminitis in Intrahepatic Cholestasis of Pregnancy: An Atypical Presentation
Authors: Randhawa Tejinder , Almoghrabi Anas , Agrawal Rohit , Omar Yazan Abu , Vohra Ishaan
Published: October 2019

INTRODUCTION:

Intrahepatic cholestasis of pregnancy (ICP) is a self-resolving hepatic condition noted during the second and third trimesters of pregnancy. ICP is a relatively benign condition. However in severe cases ICP can influence fetal outcomes resulting in prematurity and rarely intrauterine fetal demise. Diagnosis of ICP is clinical and suspected when pregnant patients present with moderate to severe pruritus and concomitant elevation in serum aminotransferases and/or bile acids. Total bile acid levels can rise by 10- to 25-fold, however aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels do not characteristically increase more than two times the upper limit of normal. The mainstay of treatment, ursodeoxycholic acid (UDCA) offers symptomatic relief of pruritus and may benefit fetal outcomes. Delivery of the fetus is followed by resolution of pruritus and normalization of transaminases and bile acids. Our case describes a rare presentation of ICP with marked 10-fold increase in AST and nearly 30-fold increase in ALT.

CASE DESCRIPTION/METHODS:

A 31-year-old female at 28 weeks gestation was admitted for two-day history of generalized pruritus and abnormal transaminases on surveillance testing. Past histories remarkable cholecystectomy following gallstone pancreatitis. Physical examination was benign and was without scleral icterus or jaundice. Investigations were remarkable for: alkaline phosphatase (ALK) 172, gamma glutamyl transferase (GGT) 20, AST 465, ALT 1023, and total bile acids 48.7. Further evaluations revealed negative hepatitis serologies and chronic liver disease work-up, liver doppler ultrasound without occlusion, MRCP without choledocholithiasis or other features of pancreaticobiliary pathology. The patient was started on UDCA and continued follow-up with Gastroenterology and Obstetric Clinics. Shortly after initiation of UDCA, transaminases began a steady down trend. After delivery of a healthy fetus, the patient's transaminases returned to baseline levels.

DISCUSSION:

Classically ICP presents with mild AST and ALT elevations no more than two times the upper limit of normal. In cases of ICP presenting with marked transaminitis it is important to exclude other causes of cholestasis and hepatic disease including viral hepatitis, gallstones, preeclampsia, and HELLP syndrome. With close multi-disciplinary monitoring, even severe cases of ICP can lead to favorable fetal and maternal outcomes including complete resolution of transaminitis and uncomplicated fetal delivery.
2532 Lynch Syndrome With Lung Adenocarcinoma and Their Response to Nivolumab
Authors: Tambe Ajay , Benjamin Sam , Badrinath Madhuri
Published: October 2019

INTRODUCTION:

Lynch syndrome is caused by mutations in mismatch repair genes which cause microsatellite instability (MSI). Patients with Lynch syndrome are at high risk for developing synchronously and metasynchronously developing colorectal, uterine, ovarian, stomach, small bowel, pancreatic, kidney and brain cancers; however, the risk of lung cancer is same as that of general population. Programmed death-1 (PD-1) inhibitors such has nivolumab have shown good overall response rate in patients with mismatch repair-deficient non-colorectal cancers.

CASE DESCRIPTION/METHODS:

A 72-year-old female with 57-pack-year history of smoking was diagnosed with stage IV adenocarcinoma of the transverse colon in 2007. She underwent resection of the transverse colon followed by chemotherapy. In 2016, she was diagnosed with stage IV duodenal carcinoma with metastasis to the liver. A 14.4 mm right lower lobe nodule was also seen on computed tomography (CT) scan (Figure 1). This nodule was suspected to be metastatic from the duodenal carcinoma, however, biopsy of this nodule showed it to be poorly differentiated adenocarcinoma of the lung. Staining was positive for TTF-1 and CK7 confirming it to be a primary lung cancer. Since this was a stage 1 adenocarcinoma, testing for PD-L1 expression was not done. EGFR, ROS, ALK-1 and BRAF mutations were negative. The patient's mother had breast cancer, father had lung, stomach and liver cancer while her sister had lung cancer with metastases to the brain. Given this history, familial cancer syndrome was suspected and microsatellite instability was tested. Loss of MSH2 and MSH6 was detected via immunohistochemistry (IHC) in duodenal cancer, making it a high-frequency MSI (MSI-H) tumor. Immunotherapy with Nivolumab was started in April 2017 and CT scans 8 months later showed markedly decreased size of the duodenal mass and the hepatic metastases while the lung nodule was reduced to 9.7 mm (Figure 2).

DISCUSSION:

As per the results of CHECKMATE-142 trial, immunotherapy with Nivolumab has shown durable response and disease control in pre-treated patients with DNA mis-match repair deficient/MSI-H metastatic colorectal cancer. PD-L1 tends to be expressed at higher levels in MSI-H cancers than in microsatellite-stable cancers. Even though lung adenocarcinoma was not tested for PD-L1 expression, it was likely to be high given its response to Nivolumab. The findings of this case suggest that lung adenocarcinoma in patients with Lynch syndrome may be susceptible to immune check-point blockade.
2606 Primary Immunodeficiency Manifesting as Chronic Diarrhea
Authors: Kalantri Shreyas , Shrimanker Isha , Nair Sujit , Rathi Pravin
Published: October 2019

INTRODUCTION:

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease described by reduced concentrations of immunoglobulins, mainly IgG, IgA and/or IgM. CVID affects both humoral and cell-mediated immunity, resulting in a myriad of infections. Gastrointestinal infections form the second most prevalent infections.

CASE DESCRIPTION/METHODS:

A 24-year-old Asian male presented with chronic watery stools associated with borborygmi, fatigue, and weakness since 10–12 years. He complained of increased frequency of stools, 5–6 episodes during the day and around 1–2 episodes at night. The stools were large in volume, occasionally foul-smelling but without any mucus or blood. He denied any urgency, tenesmus, precipitancy or bloating. He had an unintentional weight loss of 15 kgs in the past five years but denies loss of appetite. On arrival, he had a pulse of 82 beats/minute blood pressure of 110/70 mm Hg. Physical exam was not significant for any abnormality. Laboratory investigations showed hemoglobin of 9.7 gm/dl, sodium of 140 mEq/l, potassium of 3.2 mEq/l, calcium of 7.6 mg/dl, phosphorous of 3.3 mg/dl, total protein of 4.6 g/dl with albumin of 3.1 g/dl, alkaline phosphatase of 241 U/L. Workup for viral markers was negative. Immunoglobulin levels were IgA < 6.67 mg/dl, IgM of 42 mg/dl and IgG of 788 mg/dl. Esophagogastroduodenoscopy revealed diffuse nodularity in D1 and D2 (Figure 1) regions along with mild antral gastritis. Biopsy of the duodenal nodule revealed acute on chronic duodenitis with marked lymphoid aggregates (Figure 2) and also antral biopsy was suggestive of moderate chronic antral gastritis with lymphoid aggregates with detection of Helicobacter pylori 1 +. Colonoscopy up till the terminal ileum did not reveal any abnormality. Computed tomography of the abdomen with enterography revealed redundant sigmoid colon resulting in displacement of small bowel loops in the right half of the abdomen along with mucosal thickening and irregularity in the distal pylorus. The patient was treated with multivitamins along with replenishment of fat-soluble vitamins. He had a resolution of symptoms and was followed up on an outpatient basis.

DISCUSSION:

Patients with CVID have greater susceptibility to develop gastrointestinal malignancies and infectious and inflammatory conditions. Physicians should thus remain vigilant regarding chronic diarrhea and think of broad differential diagnosis including primary immunodeficiencies.
2612 Gastrointestinal Stromal Tumor Causing Obscure Gastrointestinal Bleeding: An Uncommon Way of Diagnosing an Uncommon Disease
Authors: Dziadkowiec Karolina N. , Satiya Jinendra , Katz Aviv
Published: October 2019

INTRODUCTION:

Gastrointestinal stromal tumors (GISTs) are neoplasms which arise from the tissue of the gastrointestinal tract or, rarely, from other intra-abdominal tissues. CT angiography can be utilized as an alternative imaging study when endoscopic and colonoscopy results are non-diagnostic. We report a case of a 59 year-old-female who presented with recurrent episodes of obscure overt gastrointestinal bleeding and was found to have a GIST.

CASE DESCRIPTION/METHODS:

A 59-year old woman with history of gastro-esophageal reflux disease presented to the emergency room with bright red blood per rectum and lower abdominal pain for one month. She reported one episode of melenic stool. Physical examination was unremarkable. Laboratory findings revealed a hemoglobin of 9.4 g/dL and a positive fecal occult blood test. Esophagogastroduodenoscopy (EGD) was non-diagnostic. Colonoscopy revealed fresh blood with clots at the terminal ileum, but no evident source of bleeding was identified. As the source of bleeding could not be accurately diagnosed with routine colonoscopy and EGD, an abdominal computed tomography angiography (CTA) was obtained. Abdominal CTA revealed a large exophytic, necrotic mass with hypervascularity to the right of the uterine fundus along with extensive vessels within the bowel wall. The mass, distal portion of the distal jejunum, portion of the terminal ileum were resected. Postoperative pathological examination revealed gastrointestinal stromal tumor (high grade, spindle cell variant). The patient is doing well at a four-month follow-up.

DISCUSSION:

Patients with GISTs can often be asymptomatic leading to a missed initial diagnosis. When symptomatic, patients often present with bleeding, anemia, mucosal ulceration or mass effect, depending on location. Occasionally they are discovered as incidental findings in radiologic imaging or as incidental findings during surgery or autopsy. Bleeding is the most common presenting symptom and is attributed to the erosion of the gastrointestinal tract lumen with tumor invasion, resulting in hematemesis, melena or anemia. This case offers a unique perspective of GIST diagnosis. In cases where a colonoscopy and EGD along with abdominal series is undiagnostic and capsule endoscopy/balloon enteroscopy are not available - CT angiography can be considered an alternative imaging procedure for the management of GIST tumors. In our case, CT angiography provided exact tumor location preoperatively allowing for appropriate surgical resection.
2638 Intestinal Pseudo-Obstruction Associated With Seropositive Myasthenia Gravis, Thymoma, and Positive CV-2 Antibodies
Authors: Gonzalez Adalberto , Castillo Michael , Rajagopalan Rajaganesh , Castaneda Daniel , Castro Fernando
Published: October 2019

INTRODUCTION:

Intestinal pseudo-obstruction (IPO) is a rare condition characterized by signs and symptoms of bowel obstruction without an identifiable mechanical cause. Antibody-mediated paraneoplastic syndromes and autoimmune diseases have been reported as two potential etiologies. We report a unique case of IPO presenting with thymoma, myasthenia gravis (MG), and positive CV-2 antibodies.

CASE DESCRIPTION/METHODS:

A 43 year old previously healthy female presented to the ED with abdominal pain, nausea and vomiting. This was her third visit to the ED in the past week for similar symptoms. On admission, laboratory studies were normal. A CT of the abdomen revealed marked gastric and small bowel distention, fecal impaction, and a mediastinal soft tissue density (Figure 1). She was initially managed medically with restriction of oral intake, intravenous fluids, and a nasogastric tube. Since she did not improve after several days, she was taken to the operating room for a diagnostic laparoscopy, which did not show evidence of mechanical obstruction. A CT chest with contrast done to investigate the mediastinal soft tissue density revealed an anterior mediastinal mass.A chest MRI had changes suggestive of a thymoma. This was subsequently confirmed by biopsy. Given the suspicion for a paraneoplastic process, multiple serologic markers were ordered. Acetylcholine receptor (AChR) antibodies and CV-2 antibodies were positive (Table 1). She was diagnosed with paraneoplastic intestinal pseudo-obstruction. The patient was treated with IV methylprednisolone and pyridostigmine with marked improvement in symptoms.

DISCUSSION:

The association of IPO as a paraneoplastic syndrome of thymoma and myasthenia gravis has been reported in only a few cases. The pathophysiology involves AChR antibodies targeting the neuronal nicotinic acetylcholine receptors present on autonomic ganglia. Our patient had positive AChR antibodies. She had no other symptoms of MG, indicating isolated autonomic dysfunction. IPO has also been associated with malignancies such as small cell lung cancer, which may be mediated by a variety of autoantibodies. Anti-Hu antibody has been most commonly implicated but was negative in this case. Anti-CV2 antibody was positive, which was reported in only one previously published case. In summary, patients with thymomas or MG should have testing for paraneoplastic antibodies; they tend to respond to treatment with immunosuppression and acetylcholinesterase inhibitors.
2647 A Case of Potentially Three Recurrences of Gallstone Ileus
Authors: Loudin Michael , Koprowski Steven T.
Published: October 2019

INTRODUCTION:

Gallstone ileus is rare in the general population; however, the proportion is much higher in older populations and one third of the affected patients suffer from serious medical comorbidities. Literature on intervention strategies are limited to retrospective reports with optimal intervention remaining unclear. Recurrence of gallstone ileus reaches 5%, which provides a unique dilemma for treatment approaches in patients already at higher peri-operative risk.

CASE DESCRIPTION/METHODS:

A 68-year-old male with prior history of hypertension and GERD presented with abdominal pain, nausea, bilious emesis, reduced flatus over 4 days. He had experienced a similar episode a few weeks prior that spontaneously resolved. Exam showed sinus tachycardia, but other vitals were normal. The abdomen was distended, tympanic, and moderately tender in the epigastrium without evidence of peritonitis. Labs were pertinent for a mild acute kidney injury, but were otherwise within normal limits. A CT abdomen/pelvis showed findings of small bowel obstruction with pneumobilia (Figure 1a). He ultimately underwent enterolithotomy yielding a 4 cm gallstone at the site of intestinal obstruction. Six months later, he returned with a similar presentation and was found with recurrence of gallstone ileus, this time with a 3 cm gallstone in the same location. He then underwent bowel resection with side-to-side jejunal anastomosis. Within two weeks of his second procedure, his symptoms returned and repeat CT showed recurrence of gallstone ileus at the former anastomosis site with a 2.0 cm partially obstructing gallstone. Given the recent surgical intervention, conservative measures were trialed and he was discharged on a full liquid diet. He was admitted two months later for cholecysectomy and resection of prior jejuno-jejunal anastomosis. The post-operative course was complicated by subhepatic fluid collection that was drained. At his 1-year follow-up, he was symptom free.

DISCUSSION:

Recurrence of gallstone ileus is not common and it is important for the medical team to consider underlying comorbidities of this population before proceeding with a complicated/multi-step surgical procedure. After review of the literature, enterolithotomy alone is the most recommended strategy for initial intervention. If a patient has minimal pre-existing co-morbidities, a staged, elective cholecystectomy and resection of chole-enteric fistula can be effective in preventing/treating recurrence.
2651 Secrets of the Ampulla: A Rare Neuroendocrine Tumor
Authors: Bofill Aliana , Mirza Zeyn , Estremera Rodolfo , Martin Jose
Published: October 2019

INTRODUCTION:

Neuroendocrine tumors (NETs) of the ampulla of Vater represent less than 0.3% of gastrointestinal NETs and less than 2% of all periampullary malignancies. There are approximately 139 cases in literature, making this rare condition a diagnostic challenge. Jaundice is the predominant symptom followed by abdominal pain. Acute pancreatitis as the initial presentation has seldom been reported. Herein we report a case of a patient who presented with acute pancreatitis and biliary obstruction secondary to an ampullary NET.

CASE DESCRIPTION/METHODS:

Case of a 74-year-old male with hypertension who reported burning epigastric pain. Denied fever, vomits, weight loss, diarrhea, flushing or dyspnea. Physical examination with epigastric tenderness. Laboratories showed elevated alkaline phosphatase 398 U/L, total bilirubin 3.4 mg/L, lipase 594 U/L and amylase 216 U/L. Contrast abdominopelvic CT showed a duodenal periampullary mass with common bile duct measuring 1.1 cm and intrahepatic and extrahepatic dilatation. Endoscopic retrograde cholangiopancreatography (ERCP) revealed an irregular, ulcerated ampullary mass. Biopsy showed poorly differentiated carcinoma. Immunostains were positive for chromogranin, synaptophysin, CK7, weakly positive for CDX-2. Negative for TTF-1 and CK20. Octreotide scintigraphy with no uptake. Somatostatin, chromogranin, and 5-hydroxy-in-dole acetic acid were normal. Patient underwent surgical treatment with pancreaticoduodenectomy.

DISCUSSION:

The rarity of ampullary NETs and its proliferation under an intact mucosa makes it difficult to detect in biopsy. Most of the time the diagnosis is based on histology and preoperative diagnosis may be challenging since they clinically present like adenocarcinoma. The usual presentation of jaundice and abdominal pain places this diagnosis low on the differential. In our case, the unusual morphologic appearance likely facilitated obtaining an assertive pre-operative diagnosis. Our patient presented with obstructive jaundice and acute pancreatitis, which occurs in less than 6% of cases. The clinical picture of ampullary NETs is easily confounded given the associated symptoms and biopsy challenges. A high index of suspicion is paramount to ensure this rare diagnosed is not missed. Pancreaticoduodenectomy has been advocated as the treatment of choice regardless of size due to high risk of occult nodal metastases. Considering this diagnosis within the differential is important given the drastically different outcomes for patients if caught early.
2675 A Rare Case of Bleeding Isolated Gastric Varices in the Setting of Non-Cirrhotic Portal Hypertension
Authors: Gonzalez Hector H. , Ohanisian Levonti , Bank Michael , Sidhu Simran
Published: October 2019

INTRODUCTION:

Non-cirrhotic portal hypertension (NCPH) is a rare manifestation of non-cirrhotic etiology, with gastric varices reported to occur in less than 10% of cases. Current literature hopes to identify cases in order to specify future diagnosis modalities and treatment. We present the second patient in the english literature to present with NCPH causing isolated Gastric Varices (IGV) in the absence of an identifiable etiology.

CASE DESCRIPTION/METHODS:

A 53 year old male with past medical history of diverticulitis presented to the emergency department with hematemesis and melena. He denied alcohol abuse or NSAID use. Physical exam showed BP 81/49 mmHg and non-radiating epigastric tenderness. Labs showed Hb10.4, platelet count 144,000, and BUN 39. Lipase, liver function and coagulation panel were normal. Ethanol, tylenol, and drug screen were negative. Viral hepatitis panel was negative. Patient was started on IV fluids, PPI, octreotide, and transfused two units PRBC. Emergent esophagogastroduodenoscopy (EGD) showed no bleeding source with adherent clot in fundus of stomach. Computed tomography (CT) of the abdomen with contrast showed a patent portal vein. Repeat EGD later showed moderate-sized IGV type I in fundus and GE junction ulceration. The varices were banded and ulceration clipped. Patient was treated with IV ceftriaxone, octreotide, and PPI. MRI of the abdomen showed 1.9 cm nodule in posterior hepatic dome, with portal hypertension. A nuclear scan of liver and spleen showed no colloid shift. Ultrasound of hepatic vessels showed no evidence of portal vein thrombosis with hepatopetal flow. Patient responded well to therapy, was initiated on beta blockers, and given appropriate outpatient follow up.

DISCUSSION:

Isolated Gastric Varices (IGV) are typically associated with thrombosed splenic vein, and occur most commonly in patients with portal hypertension. There are two main subtype: IGV1 located in the fundus, and IGV2 located in pylorus, body, and cardia. It is important to consider all possible etiologies attributable to portal hypertension when evaluating gastric varices on EGD. Despite the fact that they occur more frequently than esophageal varices, IGV carry a higher likelihood of mortality. Current treatment modalities include: airway protection, hemodynamic stabilization, somatostatin analogues, prophylactic antibiotics, and early endoscopic intervention. Additional studies are needed to further advance the knowledge of IGV, and establish a consensus on appropriate treatment modalities.