A role for B cells in facilitating defense against an NK cell-sensitive lung metastatic tumor is revealed by stress.

Stressors impair immune defenses and pose risks among cancer patients. Natural Killer cells are not the sole immune defense against tumor development. Utilizing an NK-sensitive tumor model, this study evaluated immune effects to stress and determined whether lung metastasis resulted from B cells' inability to augment tumorlytic function. Lung metastasis directly correlated with delayed lung B cell accumulation compared to NK, and T cells. Decreased interleukin-12 cytokine and CD80+ molecule expression by B cells correlated with decreased tumor lysis and increased tumor development. Thus, tumor defenses in the lung given stress exposure can depend on the B cell function.

Negative pressure wound therapy for initial management of giant omphalocele.

BACKGROUND: Current treatment of giant omphalocele includes "paint and wait" or placement of mesh or silo. These methods are associated with high complication rates. We propose negative pressure wound therapy as an alternative. METHODS: Patients born between 2009 and 2014 with giant omphalocele were included. Outcomes analyzed were duration of therapy, time to full enteral feeds, treatment related complications, wound surface area over time, type, and time to definitive closure. RESULTS: Eight patients were reviewed. The median duration of therapy was 68 days. Median time to full enteral feeds was 19 days. There were no treatment discontinuations or complications including sac ruptures, wound infections, or fistulas. Wound contraction stopped at 2 months or around 7 cm(2). All surviving patients underwent definitive closure. CONCLUSIONS: Negative pressure wound therapy is a safe and effective treatment for giant omphalocele that allows feeding, has a low complication rate, and is completed in 2 months.

The predictive value of incidental PET/CT findings suspicious for breast cancer in women with non-breast malignancies.

BACKGROUND: On occasion, patients followed with positron emission tomographic (PET)/computed tomographic (CT) imaging for nonbreast malignancies will have incidental breast findings concerning for second primary breast cancers. The aim of this study was to determine the predictive value of PET/CT imaging to identify breast cancers in these patients. METHODS: Patients with primary nonbreast malignancies and findings concerning for second primary breast cancers were identified from a prospectively acquired nuclear medicine database from January 2005 to July 2008. Chart reviews were then performed. RESULTS: Nine hundred two women underwent PET/CT imaging to evaluate nonbreast malignancies. Nine women (1%) had concerning breast findings, and 5 (56%) had subsequent breast cancer diagnoses. The positive predictive value of PET/CT imaging in these patients was 63%. Evidence of compliance with current screening guidelines was present in only 22% of these patients. CONCLUSIONS: The data suggest that findings concerning for an additional primary breast cancer should be evaluated and that age-appropriate screening tools should not be abandoned.

Incidental PET/CT findings in the cancer patient: how should they be managed?

BACKGROUND: Despite a paucity of evidence-based guidelines, the use of PET/CT (positron emission tomography/computed tomography) in the management of cancer patients is increasing. As widespread clinical application increases, unexpected radiographic findings are occasionally identified. These incidental findings are often suspicious for a second primary malignancy. The purpose of this study was to determine the clinical impact of these incidental PET/CT findings. METHODS: A query of our prospectively acquired Nuclear Medicine database was performed to identify patients with a known malignancy being staged or serially imaged with PET/CT. Patients with incidental findings suggestive of a second primary malignancy were selected. Statistical analysis was performed to determine the ability of PET/CT to identify a second primary malignancy. All PET/CT were interpreted by board certified nuclear radiologists. RESULTS: Of 3,814 PET/CT scans performed on 2,219 cancer patients at our institution from January 1, 2005, to December 29, 2008, 272 patients (12% of all patients) had findings concerning for a second primary malignancy. An invasive work-up was performed on 49% (133/272) of these patients, while 15% (40/272) had no further evaluation due to an advanced primary malignancy. The remaining 36% (99/272) had no further evaluation secondary to a low clinical suspicion determined by the treating team, a clinical plan of observation, or patients lost to follow-up. Of the 133 patients evaluated further, clinicians identified a second primary malignancy in 41 patients (31%), benign disease in 62 patients (47%), and metastatic disease from their known malignancy in 30 patients (23%). The most common sites for a proven second primary malignancy were: lung (N = 10), breast (N = 7), and colon (N = 5). Investigation of these lesions was performed using several techniques, including 24 endoscopies (6 malignant). A surgical procedure was performed in 74 patients (29 malignant), and a percutaneous biopsy was performed on 34 patients (12 malignant). The overall positive predictive value for PET/CT to detect a second primary malignancy was 31% in this subgroup. At a median follow-up of 22 months, 9 of 41 patients with a second primary were dead of a malignancy, 20 were alive with disease, and 12 had no evidence of disease. CONCLUSION: Incidental PET/CT findings consistent with a second primary are occasionally encountered in cancer patients. In our data, approximately half of these findings were benign, a third were consistent with a second primary malignancy or a metastatic focus, and the remainder were never evaluated due to physician and patient decision. Advanced primary tumors are unlikely to be impacted by a second primary tumor suggesting that this subset of patients will not benefit from further investigation. Our data suggests that, despite the high rate of false positivity, incidental PET/CT findings should be investigated when the results will impact treatment algorithms. The timing and route of investigation should be dictated by clinical judgment and the status of the primary tumor. Further investigation will need to be performed to determine the long-term clinical impact of incidentally identified second primary malignancies.

Lung and splenic B cells facilitate diverse effects on in vitro measures of antitumor immune responses.

In vitro measures of immune responsiveness toward tumors provide relevant information regarding the prevention and metastatic potential of cancer. In addition, the compartmentalization of immune responses is likely to be an important factor in dictating host antitumor immune responses. We have previously demonstrated that injection of antibody against B cells diminished pulmonary antitumor defenses. In the current study, we determined the effect of B cells on antitumor cellular responses against a lung metastatic tumor, MADB106. Lung B cells displayed sustained surface expression of CD80 and CD86, as compared to spleen B cells, in the presence of MADB106 tumor. Removal of B cells from lung lymphocyte cultures resulted in diminished IFN-gamma secretion and tumor lysis, whereas removal of B cells from spleen lymphocytes exposed to tumor resulted in elevated IFN-gamma and increased tumor lysis. Furthermore, a correlative increase in CD80 and CD86 co-stimulatory molecule expression by lung B cells was observed in mice subjected to MADB106 tumor. These findings provide additional evidence of the importance of pulmonary B cell responses in tumor defenses.

Automated sequencing of complete mitochondrial genomes from laser-capture microdissected samples.

Mitochondrial DNA mutations have been related to both aging and a variety of diseases such as cancer. Due to the relatively small size of the genome (16 kb) and with the use of automated DNA sequencing, the entire genome can be sequenced from clinical specimens in days. We present a reliable approach to complete mitochondrial genome sequencing from laser-capture microdissected human clinical cancer specimens that overcome the inherent limitations of relatively small tissue samples and partial DNA degradation, which are unavoidable when laser-capture microdissection is used to attain pure populations of cells from heterogeneous tissues obtained from surgical procedures. The acquisition of sufficient template combined with a standard set of 18 pairs of PCR primers allows for the efficient amplification of the genome. Subsequent single-stranded amplification is performed using 36 sequencing primers, and samples are run on an ABI PRISM 3100 Genetic Analyzer. The use of this procedure should allow even investigators with little experience sequencing from clinical specimens success in complete mitochondrial genome sequencing.