Near Complete Pathologic Response to PD-1 Inhibitor and Radiotherapy in a Patient with Locally Advanced Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains deadly despite advances in systemic therapies and surgical techniques. While there is increasing utilization of immune therapies across diverse cancer types, PDAC remains generally resistant to these treatments. We report a case of locally advanced PDAC treated with preoperative radiation and anti-PD-1 immunotherapy guided by preoperative PD-L1 tumor analysis. After 4 months of preoperative therapy, the patient was submitted to resection, demonstrating a near-complete pathologic response on final tumor analysis. We will discuss the relevant literature and current state of immunotherapeutics for PDAC.

Prospective evaluation of the prevalence of non-alcoholic fatty liver disease and steatohepatitis in a large middle-aged US cohort.

BACKGROUND & AIMS: Large prospective studies to establish the prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), are lacking. We prospectively assessed the prevalence and severity of NAFLD/NASH in a cohort of asymptomatic middle-aged Americans attending a colonoscopy class at a gastroenterology clinic. METHODS: Screening for NAFLD was performed using magnetic resonance (MR)-based LiverMultiScan® proton density fat fraction (LMS-PDFF). MR exams also included corrected T1 and elastography for liver stiffness measurement (LSM). FibroScan® was also used to measure LSM. Participants with predetermined abnormal imaging parameters were offered a liver biopsy. Biopsies were read in a blinded fashion with results based on the consensus by 2 expert pathologists. The prevalence of NAFLD was determined by PDFF ≥5% or by histological diagnosis of NAFLD (if biopsy data were available). The prevalence of NASH was defined by biopsy. RESULTS: Of 835 participants, 664 met the inclusion and exclusion criteria. The mean age was 56 ± 6.4 years, 50% were male, the mean BMI was 30.48 ± 5.46 kg/m2, and 52% were obese. The prevalence of NAFLD was 38% (95% CI 34-41%) and the prevalence of NASH was 14% (95% CI 12-17%). While no patient had cirrhosis on biopsy, significant fibrosis (F ≥2) was present in 5.9% (95% CI 4-8%) and bridging fibrosis in 1.6% (95% CI 1-3%). In a multivariable analysis, factors associated with the presence of NASH were race, obesity, and diabetes. CONCLUSION: Using state-of-the-art liver imaging modalities and reference biopsy, this study establishes an overall prevalence of NAFLD of 38% and NASH by biopsy of 14% in this cohort of asymptomatic middle-aged US adults. LAY SUMMARY: There are no prospective studies to determine how common is nonalcoholic steatohepatitis (NASH), the severe form of non-alcoholic fatty liver disease (NAFLD). In a large number of asymptomatic middle-aged Americans, we used a combination of state-of-the-art liver imaging methods and liver biopsy to prospectively determine the prevalence of NAFLD and NASH. NAFLD was diagnosed in 38%, NASH in 14%, and significant liver fibrosis in 6% of asymptomatic middle-aged Americans.

Thymoma-Induced Autoimmune Hepatitis: A Rare Paraneoplastic Syndrome.

Thymomas are rare neoplasms of the thymus and are often associated with immune-mediated paraneoplastic syndromes, most commonly, myasthenia gravis. The same underlying mechanism can produce antibodies to other self-antigens in various organ systems. Autoimmune hepatitis is a rare complication of thymoma. We present a 35-year-old healthy male, initially thought to have drug-induced liver injury, who was subsequently diagnosed with thymoma-induced autoimmune hepatitis, a rare syndrome of which only two previous cases have been reported.

Hepatic mast cell concentration directly correlates to stage of fibrosis in NASH.

Mast cells are present throughout the body in low numbers. We know their role in immediate hypersensitivity and the subsequent tissue damage due to release of cytokines, vasoactive amines, and lipid mediators when mast cells are activated. Recent research has found that there is an association between an increased concentration of mast cells in the liver and the severity of hepatic fibrosis in animal models. We currently don't understand the role of mast cells in the liver with regard to fibrosis. This retrospective review study investigated whether there is a correlation between stages of fibrosis and mast cell concentrations. One hundred six tissue slides were collected from a large military hospital of known cases of unremarkable liver, non-alcoholic fatty liver disease (Non-NASH NAFLD), and each stage of NASH (Non-alcoholic steatohepatitis). These were analyzed by staining the slides with tryptase to highlight and quantify the mast cell concentration in each diagnostic category. Three pathologists counted mast cells in five 400× fields (1 square mm) in both the periportal and parenchymal regions of each slide. These numbers were recorded and analyzed with a t test, demonstrating an increase in mast cells in NASH stage 3-4 fibrosis compared to unremarkable liver (35.48 versus 18.23, respectively, P < .001) and a direct correlation (r = 0.287) between the number of mast cells and the stage of fibrosis. Better characterizing the role of mast cells in the development of hepatic fibrosis gives us a greater understanding of the pathophysiology of non-NASH NAFLD and NASH and possibly a pharmaceutical target.

Cytomegalovirus Colitis Masquerading as Apple-Core Lesion after Systemic Chemotherapy in a Patient with Relapsed Acute Myeloid Leukemia.

We report the case of a 71-year-old male with relapsed acute myeloid leukemia who developed cytomegalovirus (CMV) colitis presenting as an apple-core lesion during induction chemotherapy. CMV infection occurs rarely during induction chemotherapy for acute myeloid leukemia. CMV infection is usually observed in patients with acquired immune deficiency syndrome (AIDS) and in those on immunosuppressive agents following bone marrow transplant. Although rare, CMV colitis should be considered in patients who are critically ill after systemic chemotherapy as it can cause significant morbidity and mortality.

Adenovirus-Associated Acute Appendicitis: An Under-Recognized Relationship?

OBJECTIVE: Acute appendicitis (AA) is one of the most common causes of a surgical abdomen worldwide, occurring most frequently in those age 10 to 29 years. Adenovirus (ADV) is a rare but reported cause of AA in children and a well-recognized cause of intussusception in infants and young children. Annually, about 36,000 basic military trainees (BMTs) undergo initial training at Joint Base San Antonio Lackland, Texas. Before reintroduction of the ADV 4/7 vaccine in November 2011, one-third of BMTs developed an adenoviral upper respiratory tract infection (URI) during the 8.5 weeks of training. We hypothesized that ADV may be a common cause of AA in the BMT population given their young age and high incidence of adenoviral URIs. The objective of this study was to determine the frequency with which ADV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and enterovirus were associated with AA in a population of young adults. MATERIALS AND METHODS: This study was a retrospective review of patient charts and existing pathological tissue specimens of all BMTs who underwent appendectomy at the Wilford Hall Medical Center from January 1, 2003, to August 31, 2011. Pathological tissue samples from 112 BMTs were assayed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) for viral targets. RESULTS: ADV DNA was detected in 16 of 112 samples (14%) via qPCR: ADV 4 in 13 cases, ADV B14 in 1 case, and nontypable ADV in 2 cases. IHC was positive in only the ADV B14 case (0.9%). All cases were negative for CMV, EBV, and enterovirus. CONCLUSION: By using qPCR, this study demonstrated an association between ADV and AA higher than has been previously reported: ADV was detected in 14% of AA cases in this series versus in only 0.23% of AA cases in previous studies (p < 0.01). There was no evidence of CMV, EBV, or enterovirus association with AA in this study. Comparison of qPCR to IHC shows that histologic analysis may overlook evidence of ADV in appendiceal tissue: qPCR is significantly more sensitive than light microscopy and IHC for detecting ADV in this setting. Because ADV 4 was detected in 81% of those with positive qPCR, the recently licensed live oral ADV vaccine might be useful for primary prevention against AA. Prospective studies evaluating young adults presenting with AA for evidence of infection with ADV are needed to determine if a causal relationship exists.

Syphilitic hepatitis uncommon presentation of an old scourge.

BACKGROUND: Giant cell hepatitis is a rare entity in adults, accounting for 0.1% to 0.25% of liver disease in adults. Postinfantile giant cell hepatitis is often characterized by multinucleated giant cells on liver biopsy and a fulminant hepatitis. CASE REPORT: An active duty 36-year-old African-American male deployed to Kabul, Afghanistan, presented with jaundice 2 weeks after starting a testosterone analogue. He discontinued the supplement, but his jaundice persisted with up-trending bilirubin. Serologic testing was negative for hepatitis A, B, C, and E; cytomegalovirus; Epstein-Barr virus; herpes simplex virus; and human immunodeficiency virus. Evaluation for autoimmune hepatitis was negative. Magnetic resonance cholangiopancreatography was negative for obstruction. Liver biopsy revealed giant cell transformation of numerous hepatocytes and cholestatic hepatitis. Rapid plasma reagin was positive without physical findings. Treponema pallidum hemagglutination assays confirmed the diagnosis of latent syphilis. He was started on penicillin treatment with rapid improvement of bilirubin, creatinine, and hepatic synthetic function, all of which eventually normalized. CONCLUSION: Postinfantile giant cell hepatitis is a severe form of hepatitis that has several different potential etiologies, 2 of which were present in this patient: androgenic supplements and infection. This case highlights syphilis as an unusual but treatable cause of giant cell hepatitis. Testing for syphilis should be considered in any persistent liver injury.

Increased IgG4+ cells in duodenal biopsies are not specific for autoimmune pancreatitis.

Endoscopic ampullary biopsies showing increased immunoglobulin (Ig) G4+ plasma cells have been reported as an alternative to pancreatic biopsy in diagnosing autoimmune pancreatitis (AIP). This study assessed whether increased IgG4+ cells can be seen outside the context of AIP. Fifty-four cases (45 duodenal or ampullary biopsies, 9 ampullae from pancreatic resections) were selected, and all specimens were immunostained for IgG4 and IgG. Duodenal or ampullary biopsies containing normal duodenal mucosa (n = 6) and increased intraepithelial lymphocytes without villous blunting (n = 7) were negative for IgG4. Increased IgG4+ cells (>10 per high-power field) were found in 7 cases of 18 serologically confirmed celiac disease patients and in 3 of 14 patients with duodenitis or gastric heterotopias. Two of 6 ampullae from patients with pancreatic cancer showed increased IgG4+ cells. In summary, 12 of 51 patients without AIP had duodenal biopsies or ampullae showing increased IgG4+ plasma cells. The finding of increased IgG4+ cells in duodenal biopsies is not specific for AIP without the correct clinical context.