Pancreatic cancer with synchronous peritoneal and hepatic metastases: A case report.

Introduction and importance: There is evidence that patients with limited peritoneal carcinomatosis of pancreatic cancer or those with low burden of hepatic metastases are amenable to surgical resection. A case report of a patient with cancer of the pancreatic tail and synchronous peritoneal and hepatic metastases is presented. CASE PRESENTATION: A male patient, 66 years old, underwent cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) and radio-frequency ablation (RFA) for synchronous hepatic metastases simultaneously to distal pancreatectomy for adenocarcinoma of the pancreas. Adjuvant chemotherapy followed the R0 surgery. The patient remained disease free for 18 months, developed liver recurrence and died 28 months after the initial operation. DISCUSSION: CRS plus HIPEC with synchronous ablation or resection of hepatic metastases may be used for the treatment of pancreatic cancer with synchronous peritoneal and hepatic metastases in highly selected patients. CONCLUSION: Further studies are needed to confirm whether patients with synchronous peritoneal and hepatic metastases are offered survival benefit from complex surgical intervention (CRS plus HIPEC combined with hepatic resection or RFA).

Immunoproliferative Small Intestinal Disease in a Liver Transplant Recipient: A Case Report and Literature Review.

Immunoproliferative small intestinal disease is an extranodal marginal zone B-cell lymphoma that arises from mucosa-associated lymphoid tissue and is associated with defective α heavy chain protein secretion. We present a case of an 18-year-old male patient admitted with diarrhea and weight loss who had previously received a liver transplant at the age of 19 months to treat biliary atresia. He underwent a thorough investigation and was diagnosed with immunoproliferative small intestinal disease lymphoma. The patient was switched from tacrolimus to everolimus and commenced on doxycycline treatment for 6 months and achieved long-term remission. Currently, 7 years after diagnosis, he is asymptomatic without evidence of histological relapse. This is the first case of immunoproliferative small intestinal disease described in a liver transplant recipient.

A Novel mHealth Monitoring System during Cycling in Elite Athletes.

BACKGROUND: Cycling is a very demanding physical activity that may create various health disorders during an athlete's career. Recently, smart mobile and wearable technologies have been used to monitor physiological responses and possible disturbances during physical activity. Thus, the application of mHealth methods in sports poses a challenge today. This study used a novel mobile-Health method to monitor athletes' physiological responses and to detect health disorders early during cycling in elite athletes. METHODS: Sixteen high-level cyclists participated in this study, which included a series of measurements in the laboratory; health and performance assessments; and then application in the field of mHealth monitoring in two training seasons, at the beginning of their training period and in the race season. A field monitoring test took place during 30 min of uphill cycling with the participant's heart rate at the ventilatory threshold. During monitoring periods, heart rate, oxygen saturation, respiratory rate, and electrocardiogram were monitored via the mHealth system. Moreover, the SpO2 was estimated continuously, and the symptoms during effort were reported. RESULTS: A significant correlation was found between the symptoms reported by the athletes in the two field tests and the findings recorded with the application of the mHealth monitoring method. However, from the pre-participation screening in the laboratory and from the spiroergometric tests, no abnormal findings were detected that were to blame for the appearance of the symptoms. CONCLUSIONS: The application of mHealth monitoring during competitive cycling is a very useful method for the early recording of cardiac and other health disorders of athletes, whose untimely evaluation could lead to unforeseen events.

Prognostic impact of stromal and intratumoral CD3, CD8 and FOXP3 in adjuvantly treated breast cancer: do they add information over stromal tumor-infiltrating lymphocyte density?

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and their subsets contribute to breast cancer prognosis. We investigated the prognostic impact of CD3+, CD8+ and FOXP3+ TILs in patients with early intermediate/high-risk breast cancer treated with adjuvant anthracycline-based chemotherapy within two randomized trials conducted by our Group. METHODS: We examined 1011 patients (median follow-up 130.9 months) and their tumors for total, stromal (s) and intratumoral (i) CD3, CD8 and FOXP3 lymphocyte density (counts/mm2) on tissue-microarray cores by immunohistochemistry. Morphological sTIL density on whole H&E-stained sections was also evaluated. RESULTS: The majority of TILs were CD3+. Total CD3 and CD8, sCD3 and sCD8, iCD3 and iCD8, sFOXP3 and iFOXP3 were strongly correlated (Spearman's rho values > 0.6). High individual lymphocytic subsets and sTIL density were strongly associated with high tumor grade, higher proliferation and HER2-positive and triple-negative tumors (all p values < 0.001). Higher sTIL density (10% increments), high density of almost each individual marker and all-high profiles conferred favorable prognosis. However, when adjusted for sTIL density, stromal and intratumoral lymphocytic subsets lost their prognostic significance, while higher sTIL density conferred up to 15% lower risk for relapse. Independently of sTIL density, higher total CD3+ and CD8+ TILs conferred 35% and 28% lower risk for relapse, respectively. CONCLUSIONS: Stromal and intratumoral CD3+, CD8+ and FOXP3+ TIL density do not seem to add prognostic information over the morphologically assessed sTIL density, which is worth introducing in routine histology reports.

Ideal treatment strategy for chylous mesenteric cyst: a case report.

BACKGROUND: A mesenteric chylous cyst is defined as a cyst occurring in the mesentery of the gastrointestinal tract anywhere from the duodenum to the rectum and is diagnosed most often during the fifth decade of life. CASE PRESENTATION: In our case report, we describe a case of 38-year-old Greek woman who presented at our Emergency Department complaining of abdominal pain without any other symptoms. Her medical and family histories were clear and she had never had any abdominal interventions. During an imaging examination with ultrasound of her abdomen, an anechoic lesion in her upper left abdomen was revealed. In a further investigation with computed tomography, a well-defined hypodense cystic 7.08 × 6.05 cm mass with mild enhancement was noted. The mass was excised by open laparotomy within healthy borders and the specimen was sent for pathological examination. The histopathological findings were found to be most consistent with a simple lymphatic (chylous) cyst of the mesentery. A review of the literature considering this rare entity was also performed to evaluate our treatment strategy and the result was analyzed. CONCLUSIONS: Chylous cysts represent a diagnostic challenge and they should be considered when a physician encounters an intraabdominal mass. Physical examination and imaging do not always provide a diagnosis and surgical management should be advised due to the potential complications that may develop.

PTTG-1 (Securin) immunoexpression in meningiomas correlates with tumor grade and proliferation rate: potential use as a diagnostic marker of malignancy.

This study essentially aims to contribute to the immunohistochemical investigation of the use of pituitary tumor transforming gene (PTTG) as a marker of cell proliferation or advanced tumor grade in meningiomas of various WHO grades. In all, 51 cases were recovered in total, 21 Grade-I, 23 Grade-II and 7 Grade-III meningiomas. Mitotic index (MI), Ki-67/MiB-1 positivity percentage and PTTG expression were analyzed in correlation to each other as well as to the tumor WHO grades. All three biomarkers showed a high diagnostic significance and a strong association with WHO grades. In comparison, PTTG expression was on a par with the other two indices, and performed very well regarding identification of advanced grade tumors. PTTG may be considered an important diagnostic tool and serve in the future as a novel prognosticator of the biological behavior of all grade meningiomas as well as a useful high-risk patient selection tool.

TdT expression in normal and neoplastic sebaceous cells.

AIMS: Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase expressed in immature, normal and neoplastic, lymphoid or haematopoietic cells and in neuroendocrine carcinomas, such as Merkel cell carcinoma and small-cell carcinoma. It has not yet been described in cells of epithelial origin. After observing TdT immunoreactivity in normal sebaceous glands, we analysed its spectrum of expression in cases of sebaceous cell hyperplasia (SGH) and sebaceous cell neoplasm. METHODS AND RESULTS: Twelve cases of SGH and three cases of other benign lesions, namely sebaceoma, sebaceous adenoma, and sebaceous naevus, along with four archived cases of sebaceous cell carcinoma (SC) were collected and stained with TdT antibody. In addition, tissue microarrays were constructed from 11 cases of basal cell carcinoma (BCC) and 10 cases of squamous cell carcinoma (SCC), which had nine evaluable cases each, and, after carcinoma type confirmation with immunostaining for epithelial membrane antigen, TdT immunohistochemistry was performed. All cases of SGH and sebaceous cell neoplasm were positive for TdT. The staining intensity was variable, being often weak to moderate in a significant proportion of cells, apart from one case of SC and the case of sebaceous naevus, which were only focally positive. No BCCs and only one SCC showed immunoreactivity. CONCLUSIONS: TdT protein can be found in cells of epithelial origin and specifically sebaceous cells, both benign and malignant. It can be hypothesized that this expression is due to sebaceous cell differentiation as a prelude to apoptosis and holocrine secretion. Additional studies are needed to further elucidate its biological role.

The cellular microenvironment and neoplastic population in mycosis fungoides skin lesions: a clinicopathological correlation.

The cellular microenvironment has been proven to play a crucial role in solid tumours and seems to be important in haematologic malignancies, however, it has not been adequately investigated in primary cutaneous T cell lymphomas. The aim of this study was to register the composition of the cellular microenvironment in mycosis fungoides skin lesions and correlate the composing parameters with the clinical data and follow-up results. The presence of eosinophilic polymorphonuclear leukocytes, B lymphocytes, CD68+ macrophages, and CD1a+ epidermal Langerhans and antigen-presenting dermal dendritic cells, as well as their relation to clinicopathological parameters, were studied in 16 mycosis fungoides cases of different disease stages. The presence and nature of the participating T cell populations was also investigated. CD8+ tumour infiltrating T cells and CD56+ cells were found among neoplastic CD4+ T cells in the lesions. Generally, eosinophils and B lymphocytes were absent or in low numbers, regardless of clinical presentation, contrary to tumourous lesions. Macrophages and CD1a+ cells were constantly present, even in early-stage mycosis fungoides. The reduced presence of the CD1a+ population was associated with resistance to therapy (x2; p = 0.012). There is a striking difference in cellular microenvironment composition between early and advanced mycosis fungoides lesions.

A rare case of a spontaneous neck hematoma in a patient with type 1 neurofibromatosis.

Neurofibromatosis type 1 (NF-1) is a genetic disorder that affects one in 3000 individuals. Although NF-1 notably involves nerves and connective tissue, vascular involvement in large series is estimated to range from 0.4% to 6.4%. Jugular vein involvement in these patients is rare. Spontaneous neck hematomas and hemorrhages are also unusual. We present a case of a NF-1 patient with a spontaneous neck hematoma with possible leakage from the left internal jugular vein, presenting as a lateral neck mass. The fragility of the vein wall and the surrounding tissue led patient to a severe intraoperative bleeding. Pathological examination revealed degenerated neurofibroma which was in contact with or infiltrated the vein wall. ENT and other clinicians should be aware of this potentially fatal entity considering that it may present as a lateral neck mass.

Bilateral Aleukemic Myeloid Sarcoma of the Eyelids With Indolent Course.

Leukemic infiltrates may be seen in the skin in the absence of detectable bone marrow involvement. Leukemia cutis may exceptionally occupy the eyelids. An unusual case of a 58-year-old man presenting bilateral erythematous eyelid lesions, proven to be aleukemic leukemia cutis, is reported. Biopsy was conducted and hematoxylin/eosin stained sections were histologically evaluated. Immunohistochemistry was also performed.Light microscopy revealed cutaneous infiltration by a neoplastic population consisting of medium-sized cells. These cells infiltrated the overlying epidermis leading to focal microulcerations. The morphological and immunohistochemical characteristics of the neoplastic population were compatible with myeloid leukemia cutis. The bone marrow biopsy was normocellular for the patient's age. Although chemotherapy was advised, the patient refused any treatment. He remains free of leukemia or evolution of eyelid lesions approximately 1 year after diagnosis. Leukemia cutis of the eyelids is a rare manifestation of acute leukemia and may remain aleukemic in adults for an indefinite period of time.

Parathyroid adenoma with prominent lymphocytic infiltrate.

Only very few previously reported cases of pronounced lymphocytic infiltration in parathyroid adenoma can be found in the English medical literature. The objective of this report is to present such a rare case and to investigate to a certain extent the immunohistochemical profile of this rare histologic observation. The lymphoid cell population within the tumour was composed of nodule-forming B-cells and different subsets of infiltrating T-cells and caused minimal destruction of neoplastic tissue.

A sequential Monte Carlo framework for haplotype inference in CNV/SNP genotype data.

Copy number variations (CNVs) are abundant in the human genome. They have been associated with complex traits in genome-wide association studies (GWAS) and expected to continue playing an important role in identifying the etiology of disease phenotypes. As a result of current high throughput whole-genome single-nucleotide polymorphism (SNP) arrays, we currently have datasets that simultaneously have integer copy numbers in CNV regions as well as SNP genotypes. At the same time, haplotypes that have been shown to offer advantages over genotypes in identifying disease traits even though available for SNP genotypes are largely not available for CNV/SNP data due to insufficient computational tools. We introduce a new framework for inferring haplotypes in CNV/SNP data using a sequential Monte Carlo sampling scheme 'Tree-Based Deterministic Sampling CNV' (TDSCNV). We compare our method with polyHap(v2.0), the only currently available software able to perform inference in CNV/SNP genotypes, on datasets of varying number of markers. We have found that both algorithms show similar accuracy but TDSCNV is an order of magnitude faster while scaling linearly with the number of markers and number of individuals and thus could be the method of choice for haplotype inference in such datasets. Our method is implemented in the TDSCNV package which is available for download at http://www.ee.columbia.edu/~anastas/tdscnv.

Maximum-parsimony haplotype frequencies inference based on a joint constrained sparse representation of pooled DNA.

BACKGROUND: DNA pooling constitutes a cost effective alternative in genome wide association studies. In DNA pooling, equimolar amounts of DNA from different individuals are mixed into one sample and the frequency of each allele in each position is observed in a single genotype experiment. The identification of haplotype frequencies from pooled data in addition to single locus analysis is of separate interest within these studies as haplotypes could increase statistical power and provide additional insight. RESULTS: We developed a method for maximum-parsimony haplotype frequency estimation from pooled DNA data based on the sparse representation of the DNA pools in a dictionary of haplotypes. Extensions to scenarios where data is noisy or even missing are also presented. The resulting method is first applied to simulated data based on the haplotypes and their associated frequencies of the AGT gene. We further evaluate our methodology on datasets consisting of SNPs from the first 7Mb of the HapMap CEU population. Noise and missing data were further introduced in the datasets in order to test the extensions of the proposed method. Both HIPPO and HAPLOPOOL were also applied to these datasets to compare performances. CONCLUSIONS: We evaluate our methodology on scenarios where pooling is more efficient relative to individual genotyping; that is, in datasets that contain pools with a small number of individuals. We show that in such scenarios our methodology outperforms state-of-the-art methods such as HIPPO and HAPLOPOOL.

Fast and accurate haplotype frequency estimation for large haplotype vectors from pooled DNA data.

BACKGROUND: Typically, the first phase of a genome wide association study (GWAS) includes genotyping across hundreds of individuals and validation of the most significant SNPs. Allelotyping of pooled genomic DNA is a common approach to reduce the overall cost of the study. Knowledge of haplotype structure can provide additional information to single locus analyses. Several methods have been proposed for estimating haplotype frequencies in a population from pooled DNA data. RESULTS: We introduce a technique for haplotype frequency estimation in a population from pooled DNA samples focusing on datasets containing a small number of individuals per pool (2 or 3 individuals) and a large number of markers. We compare our method with the publicly available state-of-the-art algorithms HIPPO and HAPLOPOOL on datasets of varying number of pools and marker sizes. We demonstrate that our algorithm provides improvements in terms of accuracy and computational time over competing methods for large number of markers while demonstrating comparable performance for smaller marker sizes. Our method is implemented in the "Tree-Based Deterministic Sampling Pool" (TDSPool) package which is available for download at http://www.ee.columbia.edu/~anastas/tdspool. CONCLUSIONS: Using a tree-based determinstic sampling technique we present an algorithm for haplotype frequency estimation from pooled data. Our method demonstrates superior performance in datasets with large number of markers and could be the method of choice for haplotype frequency estimation in such datasets.

A unified framework for haplotype inference in nuclear families.

Many large genome-wide association studies include nuclear families with more than one child (trio families), allowing for analysis of differences between siblings (sib pair analysis). Statistical power can be increased when haplotypes are used instead of genotypes. Currently, haplotype inference in families with more than one child can be performed either using the familial information or statistical information derived from the population samples but not both. Building on our recently proposed tree-based deterministic framework (TDS) for trio families, we augment its applicability to general nuclear families. We impose a minimum recombinant approach locally and independently on each multiple children family, while resorting to the population-derived information to solve the remaining ambiguities. Thus our framework incorporates all available information (familial and population) in a given study. We demonstrate that using all the constraints in our approach we can have gains in the accuracy as opposed to breaking the multiple children families to separate trios and resorting to a trio inference algorithm or phasing each family in isolation. We believe that our proposed framework could be the method of choice for haplotype inference in studies that include nuclear families with multiple children. Our software (tds2.0) is downloadable from www.ee.columbia.edu/∼anastas/tds.