Jeffrey P. Baliff

Spectrum of Pulmonary Neuroendocrine Cell Proliferation: Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia, Tumorlet, and Carcinoids

OBJECTIVE The objectives of this article are to review the radiologic, pathologic, and clinical features of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, tumorlet, and carcinoids and to discuss the possible role of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and tumorlet in the development of carcinoids. CONCLUSION Given the potential significant morbidity of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and its neoplastic counterparts, it is important to understand and recognize these disease entities. A conceptual continuum of these neuroendocrine entities is suggested.

Calorie restriction delays the progression of lesions to pancreatic cancer in the LSL-KrasG12D; Pdx-1/Cre mouse model of pancreatic cancer

Since pancreatic cancer is a lethal disease, developing prevention strategies is an important goal. We determined whether calorie restriction would prevent the development and delay progression of pancreatic intraepithelial neoplasms to pancreatic ductal adenocarcinoma (PDA) in LSL-KrasG12D/+; Pdx-1/Cre mice that develop all the precursor lesions that progress to PDA. Eight-week-old LSL-KrasG12D; Pdx-1/Cre mice were assigned to three groups: (1) ad libitum (AL) fed the AIN93M diet or (2) intermittently calorie restricted (ICR) a modified AIN93M at 50% of AL intake followed by one week intervals at 100% of AL intake, or (3) chronically calorie restricted (CCR) an AIN93M diet at 75% of AL intake. AL fed mice had a greater percentage of pancreatic ducts with PanIN-2 (13.6%) than did the ICR (1.0%) and CCR groups (1.6%), P < 0.0001. Calorie restriction (ICR [0%] and CCR [0.7%]) reduced the percentage of ducts with PanIN-3 lesions compared to the AL group (7.0%), P < 0.0001. The incidence of PanIN-2 or more lesions was significantly reduced in both ICR (27%; n = 16) and CCR (40%) mice (n = 15; P < 0.001) compared to AL (70%) fed mice (n = 11). The delayed progression of lesions in ICR and CCR mice was associated with reduced proliferation measured by proliferating cell nuclear antigen staining, reduced protein expression of Glut1, increased protein expression of Sirt1, increased serum adiponectin, and decreased serum leptin. CCR resulted in decreased phosphorylated mammalian target of rapamycin and decreased serum insulin-like growth factor-1. In summary, this is the first study to show in LSL-KrasG12D; Pdx-1/Cre mice that ICR and CCR delay the progression of lesions to PDA.

Chronic Liver Disease: Noninvasive Subharmonic Aided Pressure Estimation of Hepatic Venous Pressure Gradient

PURPOSE To compare subharmonic aided pressure estimation (SHAPE) with pressure catheter-based measurements in human patients with chronic liver disease undergoing transjugular liver biopsy. MATERIALS AND METHODS This HIPAA-compliant study had U.S. Food and Drug Administration and institutional review board approval, and written informed consent was obtained from all participants. Forty-five patients completed this study between December 2010 and December 2011. A clinical ultrasonography (US) scanner was modified to obtain SHAPE data. After transjugular liver biopsy with pressure measurements as part of the standard of care, 45 patients received an infusion of a microbubble US contrast agent and saline. During infusion, SHAPE data were collected from a portal and hepatic vein and were compared with invasive measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student t test. RESULTS The 45 study patients included 27 men and 18 women (age range, 19-71 years; average age, 55.8 years). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the hepatic venous pressure gradient (HVPG) (R = 0.82). Patients at increased risk for variceal hemorrhage (HVPG ≥ 12 mm Hg) had a significantly higher mean subharmonic gradient than patients with lower HVPGs (1.93 dB ± 0.61 [standard deviation] vs -1.47 dB ± 0.29, P < .001), with a sensitivity of 100% and a specificity of 81%, indicating that SHAPE may be a useful tool for the diagnosis of clinically important portal hypertension. CONCLUSION Preliminary results show SHAPE to be an accurate noninvasive technique for estimating portal hypertension.

In situ hybridization for Coccidioides immitis 5.8S ribosomal RNA sequences in formalin-fixed, paraffin-embedded pulmonary specimens using a locked nucleic acid probe: a rapid means for identification in tissue sections.

Coccidioides immitis/Coccidioides posadasii are common causes of pulmonary infection in certain geographic areas, and are highly infectious when working with culture isolates in the laboratory. Rapid techniques to accurately identify this pathogen in tissues may be of benefit for diagnosis and in limiting the exposure of laboratory personnel to this agent. Locked nucleic acids (LNA) are modified nucleotides in which a ribonucleoside is linked between the 2′-oxygen and the 4′-carbon atoms with a methylene unit. LNA oligonucleotides exhibit increased thermal stability and make excellent probes for in situ hybridization (ISH). In this study, ISH utilizing a biotin-labeled LNA probe targeting Coccidioides sp. ribosomal RNA sequences in 6 formalin-fixed, paraffin-embedded pulmonary tissue specimens from 6 patients with culture positive or histologic findings suggestive of Coccidioides sp. infection is described. The cultures of the pulmonary specimens confirmed C. immitis in 3 of 6 patients. The ISH procedure with the LNA probe was positive in all 6 cases, although the number of organisms that were highlighted varied from rare to numerous. ISH with a biotin-labeled DNA probe of the same sequence was positive in 4 of the 6 cases and the signal intensity and number of organisms was much less than that observed with the LNA probe. Negative control tissues containing a variety of different fungal pathogens including Aspergillus sp., Fusarium sp., Blastomyces dermatitidis, Candida sp, Histoplasma capsulatum, and Zygomyces did not hybridize with the LNA and DNA probes. ISH with an LNA oligonucleotide probe targeting Coccidioides sp. ribosomal RNA is useful for rapid ISH. ISH could be rapidly performed when fungal pathogens are observed in tissue but cultures are negative or have not been performed.

Acute Small-Bowel Obstruction From Intestinal Anisakiasis After the Ingestion of Raw Clams; Documenting a New Method of Marine-to-Human Parasitic Transmission

Enteric anisakiasis is a known parasitic infection. To date, human infection has been reported as resulting from the inadvertent ingestion of the anisakis larvae when eating raw/undercooked fish, squid, or eel. We present a first reported case of intestinal obstruction caused by anisakiasis, after the ingestion of raw clams.

A case of periampullary adenocarcinoma in neurofibromatosis type 1

Neurofibromatosis type 1 (NF-1) is an autosomal dominant genetic disorder with a known predisposition to gastrointestinal neoplasms such as stromal tumors and carcinoids. Adenocarcinomas (ACs) of the gastrointestinal tract are relatively rare in patients with NF-1, especially those found in the periampullary region. We present a case report of periampullary adenocarcinoma in a 56-year-old woman with NF-1 who presented with abdominal pain and obstructive jaundice.

Abstract B4: Calorie restriction prevents the development of pancreatic cancer in Kras; Pdx-1Cre mice

Pancreatic cancer progresses over many years, which offers the opportunity for early detection and prevention. Studies have identified elevated body mass index as a risk factor for pancreatic cancer. Lowering body weight by calorie restriction has long been associated with extended life expectancy and reduced tumor incidence in laboratory animals. Chronic and intermittent calorie restriction has a powerful protective effect against tumor development. This proposal addresses the hypothesis that intermittent calorie restriction will prevent the development and delay the progression of preneoplastic to neoplastic pancreatic lesions. The Kras; Pdx-1Cre mouse model provides an opportunity to study the efficacy of calorie restriction during the preinvasive state. At 8 weeks of age Kras; Pdx-1Cre mice were (1) fed ad libitum a purified diet based on the AIN93M recommendations (control), or (2) a modified AIN 93M diet in which mice were fed in one-week intervals at 50% of ad libitum intake followed by one week of feeding at 100% of ad libitum intake (intermittent group), or fed a modified AIN 93M diet at 75% of ad libitum intake. Food intake was measured daily and body weights were recorded weekly. At 44 weeks of age, mice were sacrificed and blood was obtained to measure serum insulin-like growth factor (IGF-1) and adiponectin; the pancreases were evaluated histologically for PanIn lesions and pancreatic ductal adenocarcinoma (PDA). Control mice gained more weight than restricted groups (p Citation Information: Cancer Prev Res 2011;4(10 Suppl):B4.

New developments in prenatal screening for Down syndrome.

Since the introduction of the triple screen, the emergence of additional analytes found to be associated with trisomy 21 pregnancies has challenged the clinical pathology and obstetric communities to determine which combination provides the best performance characteristics as a screening test. The cost, practicality, and psychosocial and ethical dimensions of different screening regimens further complicate the issue. This review attempts to give an overview of the various markers, current methods of screening, and most promising recent developments in antenatal screening for Down syndrome, with an emphasis on performance in prospective studies that have emerged during the last few years, rather than on estimates from statistical modeling.

EBV-associated Peripheral T-Cell Lymphoma of Gastrointestinal Tract Presented With Widespread Chronic Inflammation: A Case Report.

We report a case of Epstein-Barr virus (EBV)-associated T-cell lymphoma of gastrointestinal (GI) tract from a 70-year-old white woman who initially presented with a widespread GI inflammation and gastric obstruction. Initial biopsies of the GI tract showed severe chronic inflammation in the esophagus, stomach, and the small intestine. Celiac disease and inflammatory bowel disease were ruled out. The patient was treated with partial gastrectomy. Histology showed gastric wall thickening with EBV-positive, mixed lymphocytic and plasma cell infiltration in the mucosa, and thickening and fibrosis of the submucosa. She developed EBV-associated T-cell lymphoma of the GI tract one and a half years later and expired due to multiorgan failure. The T-cell lymphoma diffusely infiltrated the GI wall without forming a mass lesion. The lymphoma expressed EBV and cytotoxic molecules but lacked common features of extranodal natural killer/T-cell lymphoma nasal type, such as angioinvasion/angiodestruction, necrosis, or CD56 expression. Immunoglobulin heavy chain (IGH) gene and T-cell receptor-γ gene rearrangements and EBV-positive cells were detected at the early stage of the disease. While IGH clones were transient, T-cell clones and EBV-positive cells progressively increased over the disease course. We conclude that this case is best classified as EBV-associated peripheral T-cell lymphoma of GI tract. Age-related immune senescence may have contributed to the uncontrolled GI inflammation and subsequent transformation to T-cell lymphoma.

Perforation of a Long-standing Ileocolonic Anastomosis During Colonoscopy.

Colonoscopy is a valuable diagnostic and therapeutic procedure. Colonic perforation is a serious complication of colonoscopy that must be promptly recognized to limit morbidity and mortality. We present a 69-year-old woman who, during colonoscopy, had a perforation secondary to barotrauma of a long-standing ileocolonic anastomosis proximal to the point of colonoscopic intubation. To our knowledge, this is the first case report of a perforation of a well-established anastomosis proximal to the point of endoscope intubation during colonoscopy.