Direct trocar insertion vs. Veress needle technique in laparoscopic surgeries. A systematic review and meta-analysis.

AIM: To compare the safety and efficacy between Veress needle insertion and direct trocar insertion in laparoscopic surgeries. METHODS: Relevant clinical trials were retrieved from major databases; Web of Science, Cochrane CENTRAL, PubMed, and SCOPUS. The following outcomes were pooled for analysis: failed entry, extraperitoneal insufflation, vascular lesion, omental lesion and visceral lesion, site bleeding, reintervention, subcutaneous emphysema, solid organ lesion, and infection of the trocar site. A fixed-effects model was used to analyze homogeneous outcomes, whereas random-effects models were used to analyze heterogeneous outcomes. RESULTS: We included a total of twelve clinical trials. The pooled analysis showed that the Veress needle was accompanied by a significant increase in the incidences of extraperitoneal insufflation (RR = 0.204; 95% Cl [0.136, 0.307], P=0.001), omental lesion (RR=0.444 95% Cl [0.239, 0.825], P=0.01), and failed entry (RR=0.169 95% Cl [0.101, 0.284], P=0.001). There is no significant difference between both cohort regarding the vascular lesion (RR=0.847 95% Cl [0.259, 2.777), P=0.7), infection of the trocar site (RR=0.583 95%Cl [0.106, 3.216], P=0.5, and visceral lesion (RR=1.308 95% Cl [0.314, 5.438], P=0.7. CONCLUSION: The DTI was accompanied by a significantly lower incidence of complications such as extraperitoneal insufflation, failed entry, omental lesion, and subcutaneous emphysema. On the other hand, both cohorts showed similar results regarding; vascular lesions, visceral lesions, reintervention, site bleeding, and solid organ lesion.

Response to anti-DKK1 therapy in uterine carcinosarcoma: A case report.

Targeted therapies are being increasingly used in clinical practice and trials. However, tumor heterogeneity among sites of metastatic disease can occur creating a conundrum when utilizing biomarker directed therapies. Here we demonstrate a patient with recurrent uterine carcinosarcoma whose local recurrence and metastatic recurrence had a varied response to paclitaxel in combination with DKN-01, a monoclonal antibody against DKK1, a modulator of Wnt/ß-catenin and PI3K/AKT signaling pathways. This may be explained by differences in mutational profile found between the two sites. Our findings highlight the importance of analyzing tissue from the primary tumor as well as metastatic lesions, especially if there is a discrepancy in their response to treatment.

Investigating the role of macrophages in tumor formation using a MaFIA mouse model.

Tumor-associated macrophages (TAMs) interact with tumors in their development, growth and metastatic activities. Using a transgenic mouse model that allows for the selective depletion of macrophages we were able to access the macrophage's potential to facilitate metastasis. In the MaFIA (Macrophage Fas-Induced Apoptosis) mouse, transgene-expressing cells of the myeloid lineage undergo death by apoptosis in the presence of the drug AP20187. Enhanced green fluorescent protein (EGFP) was fused to the suicide gene to allow identification of transgene-expressing cells. Tumor induction was accomplished by subdermal and intravenous injections of B16-F10 melanoma cells. Metastasis in mice with depleted macrophages was compared to metastasis in normal control mice. The lungs and kidneys were examined for metastatic cells. The macrophage-depleted groups showed significantly less metastasis (P>0.001) compared to the control groups. We theorize that macrophages may aid the metastatic process by fusing with melanoma cells. Using appropriate cell markers and fluorescence-activated cell sorting, we were able to detect a small population of double-positive cells. We confirmed cell fusion by microscopic analysis, visualizing the cell's morphology by both immunohistochemistry and immunofluorescence. The presence of double-positive cells suggests macrophage/cancer cell fusion could be a possible mechanism for metastasis.

Phenotypic expression of ferroportin disease in a family with the N144H mutation.

Ferroportin is a putative transmembrane channel involved in the exit of iron out of the enterocytes, the macrophages and the hepatocytes. Mutations in the human gene coding ferroportin have been linked to an unusual form of iron overload, now referred to as "hemochromatosis type IV" or "ferroportin disease" characterized by a prevalent iron overload of macrophages and liver Küpffer cells. We report four patients from a same family with ferroportin disease associated with the N144H mutation. We show that in this family the mutation which is fully penetrant, may act through an increased iron export from macrophages as suggested by the unexpected absence of iron overload in the spleen and bone marrow detected by magnetic resonance imaging, that it co-segregates with a phenotype close to the classical form of HFE-associated hemochromatosis and was associated, in the oldest patient, with the development of hepatocellular carcinoma in a non cirrhotic liver. Our findings illustrate the existence of a genotype-phenotype relationship in "ferroportin disease", suggest that MRI may be useful in determining this phenotype and show that hepatocellular carcinoma may occur in these patients even without cirrhosis. This observation justifies careful follow-up of this subgroup of patients.

DNA ploidy in hepatic cirrhosis, dysplasia and carcinoma.

Hepatocellular carcinoma (HCC) is the most common and aggressive form of primary liver tumors. The evolution and the putative association of this neoplasm with hepatic cirrhosis and liver cell dysplasia remain uncertain. We analyzed the DNA ploidy by flow cytometry in a cohort of 130 liver specimens representing liver cirrhosis, hepatic cell dysplasia and hepatocellular carcinoma to determine the incidence and potential biological relevance of this feature. Our results show that four (8.0%) of the 50 cirrhotic lesions, four (26.7%) of 15 dysplastic, and 51 (78.5%) of the 65 HCC manifested DNA aneuploidy. Moreover, DNA aneuploidy was manifested in 60% of histologically negative hepatic resection margins of HCC. Our results indicate that: i) the presence of DNA aneuploidy in some cirrhotic livers and liver cell dysplasias support the potential evolution of HCC from a subset of these lesions that harbor such clonal alterations, ii) DNA aneuploidy in histologically negative resection margins of HCC in some cases support the concept of field cancerization in these tumors and iii) the predominance of DNA aneuploidy and high proliferative index (PI) in liver cell carcinomas underscore their aggressive biological behavior.

Selective suppression of nuclear retinoic acid receptor beta gene expression in human pancreatic carcinomas.

Retinoids restore normal cell growth and differentiation in malignant cells and are considered as potential therapeutic agents. Before using retinoids for the treatment of pancreatic cancer it is important to determine the expression of nuclear retinoid receptors, which mediate most actions of retinoids on gene expression in normal and malignant tissues. Digoxigenin-labeled antisense riboprobes of retinoic acid receptors (RARs) alpha, beta, and gamma, and retinoid X receptor (RXR) alpha were used for in situ hybridization to histological sections of-specimens from 24 human pancreatic carcinomas, 20 of which also contained adjacent normal tissue. All four receptors were detected in adjacent normal pancreatic tissue specimens and RAR-alpha, RAR-gamma, and RXR-alpha were also detected in all pancreatic carcinoma specimens. In contrast, RAR-beta mRNA transcripts were detected in only 67% of the malignant tissues and when expressed, the level of expression was significantly lower than that of the corresponding adjacent normal tissues. Decreased RAR-beta gene expression was especially noted in moderately- and poorly-differentiated cancers. These findings suggest that selective decrease or lass of RAR-beta gene expression in certain pancreatic carcinomas in vivo might be associated with the development or progression of pancreatic cancer.

A comparison of outpatient cardiac and pulmonary rehabilitation patients.

PURPOSE: Although cardiac and pulmonary rehabilitation are frequently considered together, differences in the two populations have not been evaluated adequately. METHODS: This study compared patients who were referred to outpatient cardiac and pulmonary rehabilitation over a 1-year period at the authors' institution. Fifty-five cardiac rehabilitation patients (CR) and 47 pulmonary rehabilitation patients (PR) were studied with respect to age, gender, weight, smoking history, functional status, employment status, numbers and types of diagnoses and medications, and number of recent hospitalizations and hospital days. RESULTS: Cardiac rehabilitation patients were approximately 7 years younger, smoked less, were somewhat heavier, had a markedly better functional status, and were more likely employed than their counterparts in pulmonary rehabilitation. In addition, this group had fewer diagnoses and used fewer medications than PR patients. The number of hospitalizations and hospital days in the year preceding rehabilitation, however, were greater in CR patients than in PR patients. CONCLUSIONS: CR patients and PR patients are quite distinct with respect to demographics, functional status, comorbidity, and hospital resource consumption.

Juvenile granulosa-cell tumor of the ovary - interphase cytogenetics for chromosome-12 and chromosome-x and flow cytometric DNA-ploidy study.

We performed interphase in situ hybridization (ISH) for chromosomes 12 and X and now cytometric DNA analysis on seven juvenile granulosa cell tumors to verify this observation and correlate the results with clinicopathologic factors. Five cases were primary ovarian tumors and two were metastatic lesions. Our results show that four tumors exhibited polysomy 12 and four had monosomy X; only two tumors displayed concurrent aberrations of both chromosomes. Of the six tumors with interpretable flow cytometric histograms three showed DNA aneuploidy and three were DNA diploid. All three aneuploid tumors manifested polysomy 12. Of the three diploid DNA neoplasms two showed monosomy X and one displayed disomy for chromosomes 12 and X. No apparent correlation between numerical chromosomal abnormalities and the biological course was observed in this small cohort. Our results indicate that chromosomes 12 and X are frequently altered in these neoplasms and thus could be targeted for further molecular studies in order to identify genetic aberrations which might be associated with JGCT tumorigenesis.

IL-2 receptor expression and ki-67 flow cytometric analysis in B-chronic lymphocytic-leukemia.

Chronic lymphocytic leukemia (CLL) is typically an indolent lympho-proliferative disorder. Its clinical course is notable for marked heterogeneity, but in a subset of patients, the disease pursues a relatively rapid clinical course. To identify patients that may have aggressive disease, the growth fraction as determined by Ki-67 proliferation marker, DNA and RNA content, and IL-2 receptor expression were determined in 46 patients with CLL by flow cytometry. Our results indicate a significant statistical correlation between Ki-67 positivity and IL-2 expression in B-CLL cells. No correlation between the proliferative activity or RNA content and IL-2 expression was found. Our data indicate that measurement of both IL-2 receptor and Ki-67 expression in B-CLL can identify a subset of patients with a high risk of rapid clinical progression.

P53 alterations show significant correlation with gene amplification and s-phase index in breast-cancer.

Correlation of p53 gene/protein alterations with incidence of oncogene amplification, a potential marker of prognosis, was evaluated in 26 fresh breast cancer samples. p53 gene was analyzed by SSCP and DNA sequencing while p53 protein status was investigated by immunohistochemistry (IH). Amplification of c-erbB2/neu, c-myc, N-ras, int-2, hst, PRAD-1 and EGFR genes was studied by slot blot and in situ hybridizations. p53 alterations were found in 31% cases by SSCP and 42% by IH; gene amplification was detected in 27% cases. p53 gene alterations correlated significantly with gene amplification (p=0.006) and also with higher S-phase index (p=0.026), aneuploidy (p=0.026) and negative progesterone receptor status (p=0.043).

Genotypic and phenotypic alterations of p53 in head and neck squamous-cell carcinoma.

p53 is the most frequently altered suppressor gene in human cancers. The genotypic and corresponding phenotypic abnormalities of this gene in head and neck squamous cell carcinoma (HNSCC) remain undefined. We analyzed the loss of heterozygosity (LOH) by restriction fragment length polymorphism (RFLP) at three polymorphic loci in the p53 gene and performed immunohistochemistry (MC) for its protein on paraffin-embedded tumor tissue from 20 previously sequenced tumor specimens. LOH was noted at one or more of the three polymorphic sites within the p53 gene in 12 (67%) of the 18 informative samples. Concordance between LOH and mutations was observed in 14 (78%) cases. Twelve (60%) tumors with point mutations were immunohistochemically reactive to p53 antibody and two (10%) lacked both genetic and immunohistochemical alterations. In six tumors (30%) contradictory results between immunohistochemistry and molecular analysis were observed. Our data indicate that: (i) simultaneous deletion and mutation of both p53 alleles was observed in the majority of head and neck squamous carcinomas and implicate this gene in the oncogenesis of these neoplasms, (ii) p53 immunohistochemical analysis may not fully account for the different molecular alterations of this gene, and (iii) no correlation between p53 abnormalities and clinicopathologic or DNA content characteristics of HNSCC was found.