Purpose of Review Hepatitis B virus reactivation (HBVr) can complicate the use of immunosuppressive, antiviral, and chemotherapeutic medications in individuals with a history of prior exposure to HBV or chronic infection. Timely management is crucial to prevent fatalities. This review focuses on the various classes of biologics linked to the risk of HBVr, with emphasis on newer immunosuppressive and immunomodulator therapies. Recent Findings Immune checkpoint inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, and chimeric antigen receptor T-cell immunotherapies are associated with a high risk of hepatitis B virus reactivation (HBVr) in patients who are hepatitis B surface antigen-positive (HbsAg-positive). This risk decreases significantly when patients start nucleoside analogue (NA) prophylaxis. It is recommended to use NA prophylaxis alongside these medications and closely monitor for reactivation upon discontinuation of NA prophylaxis. Summary To minimize the risk of reactivation when starting immunosuppressive, antiviral, and chemotherapeutic agents in individuals at high, intermediate, and low risk for hepatitis B virus reactivation (HBVr), it is crucial to employ specific strategies for risk assessment, monitoring, and management.

Introduction: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, with an annual incidence of 2%-6% in cirrhotic patients. The most common sites of metastasis are the lungs, lymph nodes, and bones. HCC metastasis to the gallbladder is rare due to HCC's infrequent invasion of the muscle layer and collagen fibers of the gallbladder wall. Here we present a case of HCC with metastasis to the gallbladder. Case Description/Methods: A 73-year-old man with a history of hypertension and diabetes presented with a 2-month history of nausea, vomiting, diarrhea, chills, and right upper quadrant pain. He denied any history of alcohol or illicit drug use, recent travel, or sick contacts. He reported a family history of colon and gastric cancer. Laboratory studies revealed an AFP of 39, WBC 12, ALT 45, AST 46, Total bilirubin 4.2, and Alk Phos 228. Hepatitis serologies and HIV were negative. CT abdomen revealed a new diagnosis of cirrhosis with chronic thrombosis of the portal vein and numerous small hepatic hypodense lesions. A follow-up MRI liver protocol was concerning for carcinoma. Endoscopic ultrasound revealed multiple hepatic lesions which were not amenable to biopsy. Four months later, the patient underwent elective cholecystectomy. Final pathology of the gallbladder revealed several tumor aggregates within the gallbladder wall and mostly within vascular structures. Immunohistochemical tumor nodules stained positively for keratin CAM 5.2, arginase, and Heppar-1, consistent with metastatic hepatocellular carcinoma to the gallbladder (Figure 1). The patient was referred to medical oncology for further management. Discussion: Metastatic HCC to the gallbladder is very rare, with an autopsy case series of 1000 patients noting the incidence to be 5.8%. The most used and recommended imaging methods are multiphasic CT and MRI. Physicians should maintain a high level of clinical suspicion as early detection is crucial for the early diagnosis and management of HCC. HCC metastasis to the gallbladder should be included in the differential diagnosis, despite its rarity. Our aim is to increase awareness, as prompt identification and timely intervention can improve patient outcomes.Figure 1.: Gallbladder biopsy. (A) Histopathological staining of the gallbladder wall reveals aggregates of tumor primarily within vascular structures (hematoxylin and eosin, 40x magnification). (B) Pathological examination of the gallbladder mucosa exhibits aggregates of tumor accompanied by a chronic inflammatory infiltrate (hematoxylin and eosin, 100x magnification). (C) Gallbladder biopsy demonstrates positive immunohistochemical staining for Arginase, confirming the diagnosis of HCC (100x magnification).

Zellweger spectrum disorders (ZSDs) are known to present with variable hepatic manifestations ranging from benign hepatosplenomegaly and elevated liver enzymes to advanced liver cirrhosis with hepatocellular carcinoma. However, the progression of liver disease in ZSD patients over time is poorly characterized due to scarcity of the disease. Herein, we report a case of newly diagnosed liver cirrhosis in a ZSD patient with rapid progression and fatal outcome to demonstrate key clinical learning points.

Purpose of Review Hepatitis B (HBV) remains a health threat around the world. Hepatitis C is closer to meeting the World Health Organization’s 2030 elimination goal compared to HBV. To achieve a successful micro-elimination and macro-elimination, there are certain objectives that need to be met. Recent Findings HBV infects more than 262 million people worldwide and is associated with significant morbidity and increased mortality. There have been previous HBV and hepatitis C virus micro-elimination trials with varying success. Micro-elimination programs should be designed to move services forward with a plethora of avenues for monitoring, testing, and treatment. Summary Ultimately, successful and maintained micro-elimination is needed to achieve macro-elimination of HBV. Here, we propose 5 core tenets of micro-elimination that can be expanded to macro-elimination; these 5-line guidelines provide for 5 pillars of HBV management that support a path to a successful global elimination of HBV.

Introduction: Acute colonic pseudo-obstruction (ACPO), referred to as Ogilvie’s syndrome, is a poorly understood condition in which there is colonic distention in the absence of underlying mechanical obstruction. ACPO may be caused by electrolyte derangements and medications that alter gut motility. Untreated ACPO can lead to devastating complications including colonic ischemia, perforation, and peritonitis. Complication risk increases directly with the duration of illness and cecal diameter. We present a case of a patient with a known history of ulcerative colitis who was found to have ACPO that failed medical therapy requiring exploratory laparotomy with subsequent total abdominal colectomy. Case Description/Methods: A 76-year-old-man with ulcerative colitis compliant with sulfasalazine, COPD, and diabetes presented with acute hypoxic respiratory failure requiring intubation, with hospital course complicated by undifferentiated shock. KUB and CT scan a day after ICU admission showed colonic distension with a cecal diameter of 12.8 cm concerning for ACPO (Figure 1). Patient was noted to have a potassium of 2.3. An NG tube was placed for decompression, electrolytes were corrected, and one dose of neostigmine was administered on the day of imaging. Unfortunately, the patient was found to have pneumoperitoneum 10 days after decompression resulting in an emergent exploratory laparotomy with subsequent total abdominal colectomy and end ileostomy. This was complicated by mucocutaneous separation of the ileostomy with subcutaneous abscess requiring ileostomy revision with I&D. The patient was subsequently discharged to a group home. Discussion: This case highlights the variability of ACPO and, to our knowledge, the first report of pneumoperitoneum complicating a course of ACPO in a patient with well-controlled ulcerative colitis. This informs the question of inflammatory bowel diseases’ association with ACPO in the setting of known compliance with home regimen. ACPO is initially managed with decompression with nasogastric or rectal tube, and correction of reversible triggers such as electrolyte abnormalities or causative medications. For those who have failed 48-72 hours of conservative measures, guidelines recommend neostigmine administration. However, some studies suggest superiority in efficacy of decompressive colonoscopy over neostigmine, although these studies have lacked power for statistical significance. Future studies clarifying the efficacy of neostigmine vs decompressive colonoscopy will be of importance.Figure 1.: A- Initial KUB revealing diffuse gaseous distention of small and large bowel loops; B- Marked gaseous distention of the large bowel 10 days after NGT decompression; C- Interval improvement in GI distention following exploratory laparotomy.

Introduction: Chronic diarrhea is most commonly seen in cases of malabsorption, chronic inflammatory processes such as inflammatory bowel disease, medication side effect, functional disorders, or persisting infections. Here we present an extreme case of constipation resulting in stercoral colitis and ultimately ischemic colitis, resulting in an unusual presentation of chronic diarrhea in the setting of constipation. Case Description/Methods: A 75-year-old woman with bipolar disorder presented with a 1-month history of abdominal pain as well as watery, nonbloody diarrhea of approximately 4 times daily. She denied recent travel, dietary changes, or sick contacts. Stool ova and parasite, culture, and PCR were all negative for infectious etiologies. Serial lactic acid recordings were normal. Abdominal CT imaging showed a thickened descending colon with significant stool burden, and the patient required an aggressive bowel regimen including enemas to relieve the stool burden (Figure 1). Subsequent colonoscopy noted segmental areas of friable and ulcerated tissue in the sigmoid colon, with random biopsies showing ulcerations and acutely inflamed granulation tissue consistent with ischemic colitis. Tissue samples were negative for granulomas, dysplasia, or malignancy. The patient had no further episodes of diarrhea following the significant bowel movement during her admission, and the patient remained without diarrhea at a 2-month follow-up. Discussion: The paradoxical presentation of diarrhea in the setting of constipation is often attributed to a phenomenon known as overflow diarrhea, where watery stool leaks around a fecalith. Overflow diarrhea is typically considered in acute, intermittent diarrhea but not chronic diarrhea, since fecaliths will eventually increase in size to seal off leaky edges and compress against colonic mucosa, resulting in inflammation of the colon known as stercoral colitis. However, stercoral colitis can rarely be complicated by ischemic colitis, which can be associated with persistent diarrhea. Our case highlights an extreme case of stercoral colitis complicated by ischemic colitis as a rare cause of chronic diarrhea, raising the importance of considering constipation as a paradoxical cause of diarrhea beyond an acute setting.Figure 1.: (A) CT imaging showing significant stool burden (B) and (C) Multiple ulcerations in the sigmoid colon noted during endoscopy.

Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease with dynamic and heterogeneous disease manifestations. Diagnosis is confirmed with elevated aminotransferases, serum antibody positivity, compatible histology, and responsiveness to steroids after exclusion of other causes. Clinical presentations of AIH can be vague, generalized, and sometimes manifestations of extrahepatic processes. Herein we present a case of AIH presenting primarily as respiratory failure with incidental findings of elevated aminotransferases. Case Description/Methods: A 23-year-old woman with no known medical history presented with dry cough, shortness of breath and right upper quadrant abdominal pain for one month. Labs on admission revealed WBC 9 k/mm3, AST 156 IU/L, and ALT 179 U/L, with increased oxygen requirements at 3L nasal cannula (baseline room air). CT imaging of the lungs revealed bilateral ground glass opacities with reverse halo sign and pleural plaques. Extensive infectious work-up including HIV, legionella, coccidioides, cryptococcus, mycoplasma, histoplasma, blastomycosis, and aspergillus was unremarkable. ANA, AMA, LKM, RF, PR3-ANCA, anti-GBM, and cryoglobulin were all negative. Mixed connective tissue diseases, scleroderma, rheumatoid arthritis were ruled out using auto-immune superpanel. ASMA was strongly positive (1:92), and atypical p-ANCA was positive 1:320. Liver biopsy was performed showing non-specific chronic inflammation. Steroids were initiated with subsequent improvement in oxygen requirements and downtrend in aminotransferases (AST 38 and ALT 85 at discharge). Discussion: AIH has a wide variety of extrahepatic manifestations; recent literature has suggested a potential involvement of the lungs through communications between the portal and pulmonary veins. Rarely, pulmonary symptoms may even be the only presenting complaint. The most sensitive and specific test for evaluation of pulmonary disease is high resolution CT scan, which may reveal non-specific interstitial or nodular changes in the pulmonary parenchyma, lung vessels, and/or pleura. As pulmonary manifestations of AIH tend to be insidious, early recognition is paramount in preventing irreversible changes secondary to pulmonary manifestations increasing mortality and morbidity in AIH (Table 1). Table 1. - 1. Fungal work up 2. Other infectious work up 3. Auto-immune work up 4. Brief metabolic work up Fungitell Negative Histoplasma Antibody Negative Coccidioides Antibodies Negative Blastomyces Antibodies Negative Crytococcal Antigen Negative Aspergillus Antibody Negative AFB Negative Bronchoalveolar lavage with fungus and respiratory culture Negative HIV-1 and HIV-2 antigen Negative Quantiferon-TB Gold Negative SARSCOV2FLURSV Negative Mycoplasma pneumoniae antibody, IgM Negative Legionella urine antigen Negative Streptococcus pneumoniae Negative Hepatitis panel Negative Rheumatoid factor Negative Auto-immune Super Panel (ANA, DNA, anti-RNP, anti-Smith, Scleroderma, SSA, SSB, Jo-1) antibodies Negative Anti-CCP antibody Negative C-ANCA and P-ANCA Negative Atypical P-ANCA Positive Anti-Smooth Muscle Antibody Strongly positive Anti-LKM Antibody Negative Myeloperoxidase Antibody Negative Anti Proteinase (Pr3) Negative Mitochondrial Antibody Negative Cardiolipin Antibody Negative Glomerular basement membrane antibody Negative Cryoglobulin Negative

(25%)werethemostcommonpriormedication.Themostcommoncorrectdiagnosiswasirritable bowel syndrome (46%) followed by solitary rectal ulcer syndrome (9.3%). The average time to correct diagnosis was 7.6 years for patients misdiagnosed with CD (range 0.6 – 25 years), and 5.4 years for those misdiagnosed with UC (range 0.3 – 14). The most common sources of diagnostic error were misinterpretation of pathology and overreliance on IBD serology testing. Conclusion: Misdiagnosis of IBD may extend for years, sometimes decades, and a quarter of patients are unnecessarily exposed to immunosuppressive medications. Irritable bowel syndrome is by far the most common diagnosis mislabeled as IBD. This study underscores the importance of careful re-evaluation of an IBD diagnosis to reduce unnecessary treatment and potentially serious consequences of mislabeling patients. To our knowledge, this study represents the fi rst detailed investigation of patients who were misdiagnosed with IBD (Figure 1).

Background and Aims: Fecal microbiota transplantation (FMT) has been increasingly studied in the inflammatory bowel disease (IBD) population. However, most studies have focused on the adult population, and the safety and efficacy of FMT in a pediatric population is less well understood. This systematic review and meta-analysis investigates the safety and efficacy of FMT in a pediatric IBD population. Methods: A comprehensive literature search of publications published prior to 30 June 2022 was undertaken. Safety data, IBD-related outcomes, and microbiome analysis were obtained from these studies when accessible. Individual estimates of each study were pooled, and sensitivity analysis was conducted. Results: Eleven studies satisfied our eligibility criteria. The calculated pooled rate of adverse events was 29% (95% confidence interval [CI]: 15.0%, 44.0%; p < 0.001; I2 = 89.0%, Q = 94.53), and the calculated pooled rate of serious adverse events was 10% (95% confidence interval [CI]: 6.0%, 14.0%; p = 0.28; I2 = 18.0%, Q = 9.79). One month after FMT, clinical response was achieved in 20/34 (58.8%) pediatric IBD patients, clinical remission was achieved in 22/34 (64.7%), and both clinical response and remission were achieved in 15/34 (44.1%) pediatric IBD patients. Conclusions: FMT can be a safe and effective treatment in the pediatric IBD population and may demonstrate improved safety and efficacy in the pediatric population compared to the adult population. However, our results are limited by a lack of established protocol as well as long-term follow-up for FMT in a pediatric IBD population.

Background and Aims: There is a high prevalence of gastrointestinal-related (GI) symptoms among children with autism spectrum disorder (ASD), which is associated with the severity of behavioral symptoms. Fecal microbiota transplantation (FMT) is a proposed therapeutic strategy that aims to address the dysregulation of the gut microbiome among children with ASD. Our study performed the first systematic review aimed to evaluate the benefits of FMT on the behavioral and gastrointestinal symptoms of pediatric patients with autism. Methods: A literature search was performed using variations of the keywords “pediatrics” and “fecal microbiota transplantation” in PubMed, EMBASE, CINAHL, Cochrane, and Web of Science from inception to 30 June 2022. Four studies that met the eligibility criteria were included in the systematic review. The efficacy of FMT on behavioral symptoms was measured by the difference in Aberrant Behavior Checklist (ABC) and Child Autism Rating Scale (CARS) scores before and after FMT. Results: We found a statistically significant improvement (p < 0.05) in ABC and CARS scores following FMT, with a statistically significant decrease in scores observed across all studies. In addition, substantial improvements in gastrointestinal symptoms were observed across all studies. Conclusion: Our findings suggest that FMT may offer a promising intervention for treating both behavioral and gastrointestinal symptoms in pediatric patients with autism.

Introduction: Inflammatory bowel disease (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC) may be challenging to diagnose. Because its presentation is often non-specific, numerous other intestinal conditions can mimic IBD, leading to misdiagnosis. In this retrospective, single-center study we investigated a series of patients misdiagnosed with IBD, aiming to describe the variables relating to the diagnostic error made. Methods: The study population was derived from consecutive patients presenting to a gastroenterology community clinic between 2016-2021. Patients ≥18 years old were included if they presented with a prior established diagnosis of IBD, had received at least one IBD specific prescription medication, had all relevant prior medical records pertaining to the time of diagnosis, and were, based on our analysis, subsequently diagnosed with another non-IBD diagnosis. The prior IBD diagnosis was removed if clinical criteria for IBD were not sufficient to establish the diagnosis. We identified the errors that led to the IBD misdiagnosis (lack of chronic inflammation on pathology, misinterpretation of laboratory tests, and overreliance on serology testing). Descriptive statistics were used to analyze the data. Results: 50 patients (54% women) met inclusion criteria. The mean age of original IBD diagnosis was 37 years (range 16-71). More patients had been misdiagnosed with CD (60%) than UC. Mesalamine/5-aminosalicyclic-acid (56.25%), followed by steroids (37.5%), and immunosuppressive agents including biologics (25%) were the most common prior medication. The most common correct diagnosis was irritable bowel syndrome (46%) followed by solitary rectal ulcer syndrome (9.3%). The average time to correct diagnosis was 7.6 years for patients misdiagnosed with CD (range 0.6–25 years), and 5.4 years for those misdiagnosed with UC (range 0.3–14). The most common sources of diagnostic error were misinterpretation of pathology and overreliance on IBD serology testing. Conclusion: Misdiagnosis of IBD may extend for years, sometimes decades, and a quarter of patients are unnecessarily exposed to immunosuppressive medications. Irritable bowel syndrome is by far the most common diagnosis mislabeled as IBD. This study underscores the importance of careful re-evaluation of an IBD diagnosis to reduce unnecessary treatment and potentially serious consequences of mislabeling patients. To our knowledge, this study represents the first detailed investigation of patients who were misdiagnosed with IBD (Figure 1).Figure 1.: Pie chart demonstrating the final diagnosis of patient's misdiagnosed with IBD. The most common correct diagnosis was irritable bowel syndrome (46%) followed by solitary rectal ulcer syndrome (9.3%), NSAID-induced ulceration (3.7%) with the remaining 41% of cases comprising ten additional diagnoses.

Introduction: Rosai-Dorfman disease (RDD) is a benign non-Langerhans cell histiocytosis that rarely involves the pancreas, of which only eighteen cases have been published to our knowledge. At least fourteen of these cases required surgical intervention. Here we present a case of pancreatic RDD diagnosed by endoscopic ultrasound with fine needle aspiration (EUS-FNA) only, thus avoiding surgical intervention for the patient. Case Description/Methods: A 49-year-old female with diabetes and hypertension presented with intermittent abdominal pain. CT scan of the abdomen showed a 4cm pancreatic body mass and a 2.3cm retroperitoneal mass. Pathology from EUS-FNA biopsies of both masses showed findings consistent with RDD. This included histiocytosis with emperipolesis, stains positive for S100, CD68, and CD163, and negative for CD1a (Figure). There were no signs of carcinoma or IgG4-related disease. Repeat CT imaging 2 years later demonstrated progressive growth of the masses. The pancreatic mass grew to 4.4cm and the retroperitoneal mass grew to 3.3cm. Repeat EUS-FNA biopsies from both sites once again demonstrated pathologic findings consistent with RDD. The patient agreed to continue routine surveillance without surgical intervention given her stable symptoms. Discussion: Most cases of pancreatic RDD have required surgical intervention for diagnosis due to initially nonspecific EUS or CT-guided biopsies. Some of these initially nonspecific biopsies were shown to have findings of RDD on re-review of pathology. While there are currently no consensus guidelines for RDD treatment, a wide array of nonsurgical options exists such as observation (as in our case), immunomodulatory agents, and chemotherapy. (Table) Increased awareness of RDD can potentially avoid unnecessary surgical intervention, thus affecting patient mortality and morbidity. We propose that pancreatic RDD does not need surgical intervention for diagnosis, and in cases of nonspecific inflammation on pathology without obvious evidence of malignancy, re-review of the pathology with a focus on RDD should be considered before surgical intervention.Figure 1.: Atypical histiocytic proliferation consistent with Rosal-Dorfman disease. Table 1. - List of all published cases of pancreatic Rosai-Dorfman Disease, including year of publication, patient age, gender, race, pancreatic location, size, and whether surgical intervention was pursued Year Age Gender Race Pancreatic location Size Surgery 1990 N/A F Black N/A N/A N/A 1999 48 F Black Body and tail 4cm Yes 2009 63 F Black Head 2.6cm Yes 2010 35 F Hispanic Tail 10.2cm Yes 2012 74 F Black Head 2cm Yes 2015 59 F N/A Head N/A Yes 2016 55 F N/A Body and tail 3.5cm Yes 2016 65 F N/A Head, body and tail 1.5cm No 2017 75 F Black Head 4.5cm No 2019 71 F Asian Tail 3.5cm Yes 2019 65 F Black Tail 1.9cm Yes 2019 65 F Black Tail 2.1cm Yes 2019 51 F Black Tail 2.9cm Yes 2019 47 M N/A Body 4.2cm Yes 2019 69 M Black Tail 2.3cm Yes 2020 40 M Black Tail 1.6cm Yes 2021 70 M White Head 4.8cm Yes 2022 78 M White Head N/A No 49 F Black Body 4.4cm No The patient of this case report is listed in the bottom row.

Introduction: Adenosquamous carcinoma of the pancreatobiliary system is a rare malignancy of the gastrointestinal tract, and uniquely unusual due to its composition of both glandular and squamous components. While it carries a worse prognosis compared to more common adenocarcinomas, adenosquamous carcinoma of the ampulla of Vater is reported to have superior postoperative mortality compared to that of the pancreas. Thus, accurate diagnosis is essential for guiding management and prognosis for the patient. Here we report a case of ampullary adenosquamous carcinoma presenting as obstructive jaundice, with imaging suggestive of a pancreatic mass but later identified as ampullary by advanced endoscopy. Case Description/Methods: A 64-year-old male with GERD presented with 3 weeks of jaundice, pale stools, and dark urine. He was noted to have a 30-pound weight loss over 3 months. He denied a family history of cancer or gastrointestinal disease. The following labs were noted: total bilirubin 22.4 mg/dL, ALP 653 U/L, AST 131 IU/L, ALT 103 U/L, lipase 642 U/L, CEA 5.4 ng/mL, and CA 19-9 4,880 U/mL. CT imaging revealed biliary and pancreatic duct dilation, as well as an ill-defined 7mm pancreatic head mass. EUS revealed a severely dilated pancreatic duct with significant atrophic pancreatic parenchyma and hyperechoic ampullary and periampullary areas. A choledochoduodenostomy was performed with biopsies of the ampulla revealing adenosquamous carcinoma, whereas biopsies of the pancreas showed only inflammatory cells. Histopathology was positive for cytokeratin 5 and 6, focally positive for cytokeratin 7, and positive for p63, which are similar to stains utilized in adenosquamous carcinoma of the pancreas (Figure). Discussion: While conventional imaging initially suggested a pancreatic malignancy for our patient, advanced endoscopy revealed a rare ampullary malignancy. The histopathology of this patient’s adenosquamous carcinoma of the ampulla of Vater resembled that of adenosquamous carcinoma of the pancreas. Postoperative mortality for the former, however, can be more favorable than the latter. This case highlights the importance of accurate distinction of pancreatobiliary adenosquamous carcinoma, and underscores advanced endoscopy as a valuable tool for achieving the correct diagnosis.Figure 1.: (Top) Biopsy of the ampullary mass was positive for immunohistochemical stains CK5/6, mostly seen in squamous cells. (Bottom) Biopsy of the ampullary mass was also positive for immunohistochemical stain CK7, mostly seen in glandular epithelium.

Introduction: Anorectal melanoma is a rare and aggressive subtype of gastrointestinal cancer, accounting for 0.5% of all colorectal cancers. Misdiagnosis of anorectal melanoma is common, as cases oftentimes present with nonspecific symptoms including hematochezia. As such, timely and accurate diagnosis of anorectal melanoma is difficult due to its rarity and nonspecific presentation. Consequently, prognosis is poor due to frequent metastasis by the time of diagnosis. Case Description/Methods: A 65-year-old male with a history of basal cell carcinoma of the cheek and tobacco use presented with 10 days of hematochezia associated with dyschezia and change in caliber of stool. The patient was noted to have a 10-pound weight loss since a positive fecal immunochemical test 5 months prior. Notably, while he had not had a colonoscopy, his records revealed a prior sigmoidoscopy for similar complaints 4 years prior. Sigmoidoscopy was negative for polyps or tumors but diagnostic of segmental colitis associated with diverticulosis (SCAD); symptoms resolved after a course of oral mesalamine and antibiotics. Family history was positive for a brother with esophageal cancer. Labs were unremarkable for anemia or liver panel abnormalities. Computed tomography imaging of the abdomen showed sigmoid wall thickening, pelvic lymphadenopathy, and multiple liver lesions. Colonoscopy revealed a 0.8 × 0.5 × 0.1 cm anal mass with biopsies consistent with malignant melanoma; stains were positive for HMB45 and negative for p40 and p63. An ultrasound-guided liver biopsy showed metastatic melanoma positive for HMB45 (Figure 1). Discussion: Hematochezia can arise from anatomical, vascular, inflammatory, and neoplastic etiologies. Although neoplastic causes are the least common, anorectal melanoma represents an especially rare and dismal diagnosis from this category. Risk factors for anorectal melanoma are unknown, although HIV has been previously suggested. HIV screening in our patient was negative. An association between anorectal melanoma and SCAD is unclear. Management of anorectal melanoma is poorly described given the scarcity of the disease but typically consists of surgical resection, although the method and extent of resection is debated. Additionally, the benefit of adjuvant chemotherapy or radiation is unclear. Prognosis of anorectal melanoma is poor, with 5-year survival rates estimated to be no more than 20-30%.Figure 1.: (Left) A 0.8 × 0.5 × 0.1 cm anal mass was detected on colonoscopy. (Top, Right) Biopsy of .the anal mass was positive for immunostain HMB45. (Bottom, Right) Biopsy of the liver mass was positive for immunostain HMB45, suggestive of metastatic anorectal melanoma.

Introduction: Ischemic hepatitis is one of the few differential diagnoses to consider in cases of severely elevated serum aminotransferases 20 times the upper limit of normal. Given the inherently robust nature of the liver despite ischemic states, ischemic hepatitis usually presents in patients requiring advanced care in an intensive care unit, and often carries a high rate of in-hospital mortality. Moreover, most cases occur in patients with underlying heart failure. Here we report a case of ischemia hepatitis in a patient not requiring intensive care and without apparent heart failure, who was successfully treated for COPD exacerbation in the setting of an influenza A infection. Case Description/Methods: A 56-year-old female with COPD presented with 3 days of dyspnea with SpO2 as low as 79% on room air. She tested positive for influenza A. She was incidentally found to have elevated aminotransferases, which peaked within 12 hours of admission, with AST of 1226 IU/L and ALT of 943 U/L, and LDH of 1300 U/L. She had unremarkable INR, bilirubin, albumin, ALP, and GGT. Hepatitis panel, acetaminophen, ethanol, alpha-1 antitrypsin, antinuclear antibody, anti-smooth muscle antibody, antimitochondrial antibody, and ceruloplasmin were also all unremarkable. CT and ultrasound of the abdomen did not suggest underlying liver disease, and echocardiogram did not suggest any heart dysfunction. She denied any recent changes to her medications but did take marijuana gummy supplements. Her aminotransferases drastically fell with standard treatment of COPD exacerbation. Oxygen supplementation was limited to nasal cannula only, and she never required intensive care. At discharge, the patient's AST was 63 IU/L and ALT was 211 U/L. Discussion: Although ischemic hepatitis is a rare diagnosis primarily diagnosed in the intensive care setting, it can be infrequently seen in the hospital ward when patients demonstrate serum aminotransferases 20 times the upper limit of normal. In the setting of infections by viruses not traditionally considered as hepatotropic, ischemic hepatitis serves as a potential mechanism for severe serum aminotransferase elevations due to a hypoxic state. Furthermore, recent research suggests that an immune-mediated response to viral infection, and not hypoxia, is what primarily drives the aminotransferase elevation.

Combining fluorescence and acoustic techniques enables the characterization of biochemical environments with optical sensors while utilizing the penetration depth and spatial resolution of focused ultrasound. Localized light generation within a small tissue volume can yield spatially resolved chemical information useful for delineating tissue pathology such as cancerous lesions. Our work develops fluorescent microbubble contrast agents that generate light in the focal zone of an ultrasound beam through modulation of their fluorescence intensity. Microbubbles were designed with a self-quenching lipophilic dye patterned within the lipid layer, enabling the dye molecules to quench and dequench with the ultrasound-driven particle size oscillations. Distinct dye patterns were generated on the microbubble surfaces and investigated for their ultrasound-driven fluorescence response. By amplifying the microbubble fluorescence intensity modulations using a lock-in amplifier, the optical signal from these locally activated particles was detected within an optically scattering environment and at significant depth. We additionally observed that these microbubbles also displayed harmonic oscillations of fluorescence intensity beyond the ultrasound driving frequency which could be used to further improve the signal-to-noise ratio for detection. This technique could enable sensitive optical imaging with ultrasound-scale millimeter-level spatial resolution, providing a valuable tool to address the challenge of optical imaging in deep tissue.