Neoadjuvant chemotherapy for pancreatic cancer: Quality over quantity.

BACKGROUND AND OBJECTIVES: The ideal duration of neoadjuvant chemotherapy (NACT) in patients with localized pancreatic adenocarcinoma (PDAC) treated with curative intent is unclear. We sought to determine the prognostic significance of both duration of NACT and Carbohydrate Antigen 19-9 (CA19-9) normalization to NACT. METHODS: We examined patients with resectable and borderline resectable PDAC treated with NACT and chemoradiation. Patients were compared by NACT duration (2 vs. 4 months) and by CA19-9 normalization after NACT. RESULTS: Among 171 patients, 83 (49%) received 2 months of NACT, and 88 (51%) received 4 months. After NACT completion, 115 (67%) patients had persistently elevated CA19-9, and 56 (33%) had normalized. Of the 125 patients who had successful surgery, 73 (58%) had normalized CA19-9 postoperatively. Duration of NACT was not associated with overall survival (OS) while CA19-9 normalization after NACT (regardless of duration) was associated with improved OS (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.35-0.89, p = 0.02). Adjuvant chemotherapy was associated with improved OS among patients without CA19-9 normalization after NACT (HR 0.42, CI 0.20-0.86, p = 0.02) but not among those that normalized, independent of duration. CONCLUSIONS: CA19-9 normalization after NACT is a clinically significant endpoint of treatment; patients without CA19-9 normalization may benefit from additional therapy.

Undifferentiated carcinoma with osteoclast-like giant cells: A pathologic-radiologic correlation of a rare histologic subtype of pancreatic ductal adenocarcinoma.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is an exceedingly rare subtype of pancreatic ductal adenocarcinoma. Histologically, UC-OGC is characterized by three cell types namely, a neoplastic mononuclear cell component, non-neoplastic osteoclast-like giant cells, and a non-neoplastic mononuclear histiocytic component. The behavior of this tumor is unpredictable; but many patients survive many years after diagnosis. UC-OGC may have a better prognosis compared to conventional pancreatic adenocarcinoma due to its slower local spread, less aggressive nature, better response to surgical resection and/or chemotherapy, and fewer metastases. Due to likely differences in prognosis and significant impact on patient management, it is important to distinguish this subtype from other types of pancreatic adenocarcinoma. We report a case of a small (<1 cm) undifferentiated carcinoma with osteoclast-like giant cells of the posterior pancreatic body discovered incidentally on magnetic resonance image (MRI) scan of a middle-aged man. The radiologic and pathologic findings are presented along with a discussion of the differential diagnosis of this exceedingly rare entity.

Clinical and Pathologic Response to Vedolizumab in a Young Female Patient With Collagenous Gastritis.

Collagenous gastritis is a rare form of gastritis that affects both children and adults. The underlying pathophysiology is not well-understood, and as a result, there are limited options for treatment. We report a case of a young female patient with chronic diffuse abdominal pain, nausea, regurgitation, and early satiety with esophagogastroduodenoscopy showing gastric erythema, atrophic gastric body, and significant gastric nodularity. Biopsies revealed focal erosion and increased subepithelial collagen deposition. She was successfully managed with intravenous vedolizumab infusions after initial therapy with topical budesonide did not result in clinical or endoscopic improvement.

Benign mature teratoma of the cecum: a case report.

A teratoma is a typically benign tumor derived from more than one embryonic cell line, and it is characterized by presence of tissue foreign to the tumor location site. With the unlikely primary location in the gastrointestinal tract and no history of malignancy, we present a rare case of a primary mature cystic teratoma of the cecum. The patient is a 66-year-old male with imaging demonstrating an extraluminal, seemingly fat-containing mass abutting the cecum. The patient underwent resection, and final pathology revealed a mature cystic teratoma. Primary mature teratoma of the cecum is exceptionally rare; thus, diagnosis can be challenging. As he had no primary testicular or retroperitoneal mass, this cystic lesion likely represents a developmental abnormality and not a true neoplasm. The radiographic features, presentation, differential diagnoses, and treatment recommendations are discussed.

Significantly Elevated Alkaline Phosphatase Caused by Congestive Hepatopathy in the Setting of Heart Failure with Preserved Ejection Fraction.

INTRODUCTION: We report a rare case of significantly elevated alkaline phosphatase (ALP) caused by congestive hepatopathy in the setting of heart failure with preserved ejection fraction (HFpEF). CASE PRESENTATION: A 44-year-old woman with multiple hospitalizations for acute decompensated HFpEF and abdominal pain had an ALP elevation to almost 8 times the upper limit of normal. A negative inflammatory, infectious, and autoimmune workup led to liver biopsy and diagnosis of congestive hepatopathy. DISCUSSION: The existing literature includes extensive research on the impact of liver function enzymes in heart failure with reduced ejection fraction (HFrEF); however, research on their impact on HFpEF is limited. ALP has been found to be normal or mildly elevated, with very few cases of significantly elevated ALP levels reported in HFrEF patients only. CONCLUSION: Complex cardiohepatic interactions often result in the coexistence of heart failure and liver disease. Unexplained chronic cholestasis in the setting of congestive heart failure should raise the suspicion for congestive hepatopathy.

Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells.

PURPOSE: Glioblastoma multiforme (GBM) remains highly incurable, with frequent recurrences after standard therapies of maximal surgical resection, radiation, and chemotherapy. To address the need for new treatments, we have undertaken a chimeric antigen receptor (CAR) "designer T cell" (dTc) immunotherapeutic strategy by exploiting interleukin (IL)13 receptor α-2 (IL13Rα2) as a GBM-selective target. EXPERIMENTAL DESIGN: We tested a second-generation IL13 "zetakine" CAR composed of a mutated IL13 extracellular domain linked to intracellular signaling elements of the CD28 costimulatory molecule and CD3ζ. The aim of the mutation (IL13.E13K.R109K) was to enhance selectivity of the CAR for recognition and killing of IL13Rα2(+) GBMs while sparing normal cells bearing the composite IL13Rα1/IL4Rα receptor. RESULTS: Our aim was partially realized with improved recognition of tumor and reduced but persisting activity against normal tissue IL13Rα1(+) cells by the IL13.E13K.R109K CAR. We show that these IL13 dTcs were efficient in killing IL13Rα2(+) glioma cell targets with abundant secretion of cytokines IL2 and IFNγ, and they displayed enhanced tumor-induced expansion versus control unmodified T cells in vitro. In an in vivo test with a human glioma xenograft model, single intracranial injections of IL13 dTc into tumor sites resulted in marked increases in animal survivals. CONCLUSIONS: These data raise the possibility of immune targeting of diffusely invasive GBM cells either via dTc infusion into resection cavities to prevent GBM recurrence or via direct stereotactic injection of dTcs to suppress inoperable or recurrent tumors. Systemic administration of these IL13 dTc could be complicated by reaction against normal tissues expressing IL13Ra1.

Yield of primary and repeat induced sputum testing for Pneumocystis jiroveci in human immunodeficiency virus-positive and -negative patients.

CONTEXT: Induced sputum sampling has an approximate 70% sensitivity for detection of Pneumocystis jiroveci in human immunodeficiency virus (HIV) patients. Bronchoalveolar lavage sampling has greater than 90% sensitivity but is a far more invasive procedure. Therefore, bronchoalveolar lavage testing is often recommended as a follow-up after a negative induced sputum. In HIV-negative patients, the utility of induced sputum testing is still not well defined. OBJECTIVE: To determine whether repeat induced sputum sampling increases diagnostic yield and might thereby reduce the need for follow-up bronchoalveolar lavage sampling. To determine the utility of induced sputum sampling in HIV-negative patients. DESIGN: A 2-year retrospective review of the utility of repeat induced sputa testing in patients with previous first and/or second negative induced sputa. Retrospective review of induced sputa detection in HIV-negative patients. RESULTS: Repeat testing of induced sputa for Pneumocystic jirovecii did not significantly increase diagnostic yield. Furthermore, in HIV-negative patients, induced sputum testing was diagnostically insensitive. CONCLUSIONS: Bronchoalveolar lavage testing should be performed initially in HIV-negative patients and after a first negative induced sputum in HIV-positive patients.