Heidi D. Lehrke

Prognostic Significance of the Histologic Response of Perihilar Cholangiocarcinoma to Preoperative Neoadjuvant Chemoradiation in Liver Explants.

Perihilar cholangiocarcinoma (pCCA) has a dismal prognosis. Protocols incorporating chemotherapy, radiotherapy, and liver transplantation (LT) have emerged as curative options for unresectable tumors with 70% 5-year survival rates. We aimed to assess the value of extent of residual tumor (ERT) and other pathologic factors following chemoradiation in predicting outcome; 152 liver explants with pCCA treated with neoadjuvant chemoradiation and LT between 1993 and 2013 were reviewed for ERT, pathologic stage, histologic grade, and perineural and lymphovascular invasion. ERT was quantified as the percentage of viable carcinoma in the tumor bed. Tumors were classified into 4 ERT categories: (1) complete/near-complete response (⩽1% ERT); (2) marked response (>1 to <10% ERT); (3) moderate response (10 to <30% ERT); and (4) minimal response (≥30% ERT). Overall 5-year survival rate was 69%. 5-year disease-free estimate was 74%. 57%, 16%, 18%, and 9% of explants were placed in ERT categories 1, 2, 3, and 4, respectively. ERT correlated significantly with the overall 5-year survival rate and 5-year, disease-free estimate by univariate (P<0.0001) and multivariate analysis (P=0.004 and 0.009, respectively). By multivariate analysis, pathologic stage was also an independent predictor of recurrence (P=0.003). Other variables that correlated with risk of death and recurrence by univariate analysis included perineural (P<0.0001) and lymphovascular invasion (P<0.0001), absence of primary sclerosing cholangitis (P=0.006 and P<0.0001, respectively), and pretreatment CA19-9 level (P=0.001 and 0.02, respectively). Histologic grade did not predict outcome. In summary, ERT independently predicts outcome in pCCA patients following neoadjuvant chemoradiation and LT and can stratify patient prognosis.

Intracardiac juvenile xanthogranuloma with presentation in adulthood.

Juvenile xanthogranuloma is the most frequent type of non-Langerhans cell histiocytosis. It most commonly presents in infancy and early childhood; manifesting as cutaneous lesions on the head, neck, and trunk that suddenly appear and usually undergo spontaneous regression. Extracutaneous involvement, although rare, may occur along with the cutaneous form or in isolation. It most frequently involves the eye, deep subcutaneous tissues, lung, and liver. Involvement of the heart is exceptionally rare, with only seven reports found in the English literature, all affecting infants. We present the first report of an intracardiac juvenile xanthogranuloma in an adult.

Undifferentiated Pancreatic Carcinomas Display Enrichment for Frequency and Extent of PD-L1 Expression by Tumor Cells

Objectives Programmed death ligand 1 (PD-L1) expression in pancreatic ductal adenocarcinoma (PDA) has been described, but unselected PDAs have shown limited clinical responsiveness to anti-programmed death 1 (PD-1)/PD-L1 therapy. Methods We studied 24 cases of undifferentiated pancreatic carcinoma (UPC) using immunohistochemistry for PD-L1 (E1L3N clone), CD3, CD20, CD68, and DNA mismatch repair proteins in this study. Slides were scored for extent of PD-L1 expression on tumor cells and tumor-infiltrating immune cells. Results PD-L1 expression was more frequent in UPCs than in PDAs (63% vs 15%, P < .01). The extent of PD-L1 expression was greater in UPCs, with 13 (87%) of 15 cases containing 10% or more positive tumor cells compared with three of seven PDAs (P = .05). Both tumor groups showed similar numbers of tumor-infiltrating T cells, B cells, and macrophages. Conclusions UPC is enriched for PD-L1 expression in frequency and extent, relative to conventional PDA. Anti-PD-1/PD-L1 agents may represent a valuable therapeutic approach for this subset of highly aggressive pancreatic carcinoma.

Red cell exchange for a case of babesiosis

During the summer months of 2014, a 67-year-old man from northern Wisconsin was admitted to the hospital with intermittent fevers, chills, vomiting, nausea, and malaise. Further questioning revealed a history of a tick bite one month prior to presentation and a past medical history significant for Hodgkin lymphoma and splenectomy. He was empirically treated with doxycycline. Several days later, he presented to the emergency department with acute renal failure, fever, and hypotension. A peripheral blood smear (Figure 1) revealed numerous red blood cells (RBCs) containing multiple, pleomorphic ring forms, and scattered extraerythrocytic organisms, consistent with Babesia sp, with an estimated parasitemia level of 28.5%. A decision was made to perform emergency RBC exchange as he began to show signs of progressive anemia, renal failure, hepatic injury, and impending respiratory compromise. A total of nine units of RBCs (2,626 mL) were exchanged using the COBE Spectra. Following treatment, his peripheral smear revealed a markedly decreased parasitemia level of 3.1% (Figure 2). The patient improved and six days later was discharged on oral atovaquone, doxycycline, and azithromycin. PCR results on samples obtained prior to the red cell exchange were positive for B. microti and negative for B. duncani and B. divergens/ MO-1. After two weeks of antibiotic therapy, no organisms could be identified on peripheral smear but PCR testing remained positive for B. microti with a decision to prolong antibiotic therapy for an additional two weeks. PCR became negative 3 months after completion of antibiotics. Red blood cell exchange is used as a second-line treatment for patients with babesiosis, in addition to the standard antibiotic regimen of atovaquone and azithromycin. The main purpose of RBC exchange is to reduce the level of parasitemia by eliminating infected RBCs and replacing them with non-infected RBCs. Additional theoretical advantages of RBC exchange include the removal of microcirculationobstructing, rigid, infected RBCs. In severe cases of babesiosis as well as high-risk populations (immunosuppressed, elderly or asplenic individuals) without evidence of organ dysfunction, the use of RBC exchange is weakly recommended as a second-line or adjunctive treatment (ASFA

Desmoid Fibromatosis Mimicking Metastatic Recurrence After Pancreatectomy for Pancreatic Adenocarcinoma

Desmoid fibromatosis is a rare, neoplastic tumor known for its aggressive local invasion and recurrence after surgery. Tumors can occur sporadically or associated with familial adenomatous polyposis. We present 3 cases of desmoid fibromatosis postpancreatectomy for pancreatic adenocarcinoma. All cases occurred within 3 years of diagnosis of pancreatic cancer, with subsequent extensive diagnostic work-up to rule out metastatic disease. No relationship between pancreatic cancer and desmoid fibromatosis is documented in the literature, with a postulated connection via mutations on the Wnt/APC/Beta-catenin pathway.

Accuracy of Endoscopic Ultrasound Imaging in Distinguishing Celiac Ganglia From Celiac Lymph Nodes

BACKGROUND & AIMS: Endoscopic ultrasound (EUS) allows visualization of celiac lymph nodes (CLNs) and celiac ganglia (CG). Reliably distinguishing these structures is important for tumor staging and CG ablative therapies. We aimed to evaluate the accuracy of EUS in distinguishing CLNs from CG using a strict cytopathology reference standard. We also determined the rate of detection of CLN and CG by conventional cross‐sectional imaging. METHODS: From EUS and cytopathology databases, we identified all patients who underwent EUS‐FNA of a presumed CLN or CG from October 1, 2004, through March 1, 2017, and compared the findings with those from cytology (reference standard). Indeterminate cytology results were re‐reviewed. EUS imaging (ie, index test) results were compared with those from the reference standard. An expert radiologist re‐reviewed computed tomography and magnetic resonance images from 100 lesions, from 94 randomly selected patients with a reference standard, to determine the rates of CLN and CG detection. RESULTS: A total of 504 patients (mean age, 63.4 ± 13.2 years; 292 men) underwent a median of 7 EUS‐FNA passes (range, 1–13) for a total of 566 lesions perceived to be either a CLN or CG; the cytology reference standard was available for 521 lesions (92.1%). When we excluded indeterminate cytology results, the EUS accurately identified 281/286 CLNs (98.3%) and 166/186 CGs (89.2%), for an overall accuracy of 447/472 (94.7%). EUS‐FNA distinguished CG from CLNs with a 93.3% sensitivity, 93.7% specificity, a positive predictive value of 96.2%, and a negative predictive value of 89.2%. Of 100 lesions in 94 patients randomly selected for a second expert radiology review, computed tomography and magnetic resonance imaging detected 59/67 CLNs (88.1%) and 13/33 CG (39.4%). CONCLUSION: EUS accurately distinguishes CLNs from CG. EUS might therefore be used to increase the accuracy of tumor staging, to select tumor stage‐appropriate therapy, and to guide CG‐ablative therapies.

Exchange transfusion for babesiosis when, how, and how long?

Babesiosis is a zoonotic disease transmitted by Ixodes ticks seen in the United States and parts of Europe. Because of the typically mild course of most infections, the disease is uncommonly seen in clinical practice. However, asplenic patients can develop a life-threatening infection. The first line of therapy for Babesia infections is antiparasitic medications; however, red blood cell (RBC) exchange transfusion has been described as an adjunct therapy. We describe a severe case of babesiosis in an asplenic patient and review the evidence, indications, and protocols for RBC exchange transfusion in this setting.