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.

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.