Altered PTEN function caused by deletion or gene disruption is associated with poor prognosis in rectal but not in colon cancer.

Colorectal cancer is the third most common malignancy worldwide. Anti-epidermal growth factor receptor (EGFR)-targeted therapy shows clinical evidence in this malignancy and improves outcome. The tumor suppressor gene phosphatase and tensin homologue (PTEN) is considered a potential predictor of nonresponse to anti-EGFR agents. The purpose of this study was to assess whether associations between PTEN alterations (PTEN gene deletion or PTEN gene disruption) and clinical outcome could be caused by a prognostic (and not predictive) effect of PTEN inactivation. Therefore, we analyzed 404 colorectal cancers not previously treated with anti-EGFR drugs in a tissue microarray format. PTEN deletion and PTEN gene rearrangements were analyzed by fluorescence in situ hybridization. Heterogeneity analysis of all available large tissue sections was performed in 6 cases with genomic PTEN alteration. Twenty-seven (8.8%) of 307 analyzable colorectal cancer spots showed genomic PTEN alterations including 24 hemizygous and 1 homozygous deletion as well as 2 PTEN gene disruptions. Genomic PTEN alterations were associated with reduced patient survival in rectal cancer in univariate and multivariate analyses (P = .012; hazard ratio, 2.675; 95% confidence interval, 1.242-5.759) but not in colon cancer. Large-section evaluation revealed a homogeneous distribution pattern in all 4 analyzed cases with PTEN deletion and in both cases with a PTEN gene disruption. In conclusion, genomic PTEN gene alterations caused by deletion or gene disruption characterize a fraction of rectal cancers with particularly poor outcome.

VEGFR-2, CXCR-2 and PAR-1 germline polymorphisms as predictors of survival in pancreatic carcinoma.

BACKGROUND: Hypoxic environment of pancreatic cancer (PC) implicates high vascular in-growth, which may be influenced by angiogenesis-related germline polymorphisms. Our purpose was to evaluate polymorphisms of vascular endothelial growth factor receptor 2 (VEGFR-2), CXC chemokine receptor 2 (CXCR-2), proteinase-activated receptor 1 (PAR-1) and endostatin (ES) as prognostic markers for disease-free (DFS) and overall survival (OS) in PC. PATIENTS AND METHODS: Genotyping of 173 patients, surgically treated for PC between 2004 and 2011, was carried out by TaqMan(®) genotyping assays or polymerase chain reaction. Chi-square test, Kaplan-Meier estimator and Cox regression hazard model were used to assess the prognostic value of selected polymorphisms. RESULTS: VEGFR-2 -906 T/T and PAR-1 -506 Del/Del genotypes predicted longer DFS (P = 0.003, P = 0.014) and OS (VEGFR-2 -906, P = 0.011). CXCR-2 +1208 T/T genotype was a negative predictor for DFS (P < 0.0001). Combined analysis for DFS and OS indicated that patients with the fewest number of favorable genotypes simultaneously present (VEGFR-2 -906 T/T, CXCR-2 +1208 C/T or C/C and PAR-1 -506 Del/Del) were at the highest risk for recurrence or death (P < 0.0001). CONCLUSION: VEGFR-2 -906 C>T, CXCR-2 +1208 C>T and PAR-1 -506 Ins/Del polymorphisms are potential predictors for survival in PC.

Surgical strategies in patients with advanced hilar cholangiocarcinoma (Klatskin tumor).

BACKGROUND: Surgical resection represents the only potentially curative treatment for hilar cholangicarcinoma. Because of the aggressive nature and the absence of effective adjuvant therapy treatment remains still a challenge. DISCUSSION: This manuscript reviews management of hilar cholangiocarcinoma with a focus on operative strategy.

Establishing aquatic restoration priorities using a watershed approach.

Since the passage of the Clean Water Act in 1972, the United States has made great strides to reduce the threats to its rivers, lakes, and wetlands from pollution. However, despite our obvious successes, nearly half of the nation's surface water resources remain incapable of supporting basic aquatic values or maintaining water quality adequate for recreational swimming. The Clean Water Act established a significant federal presence in water quality regulation by controlling point and non-point sources of pollution. Point-sources of pollution were the major emphasis of the Act, but Section 208 specifically addressed non-point sources of pollution and designated silviculture and livestock grazing as sources of non-point pollution. Non-point source pollutants include runoff from agriculture, municipalities, timber harvesting, mining, and livestock grazing. Non-point source pollution now accounts for more than half of the United States water quality impairments. To successfully improve water quality, restoration practitioners must start with an understanding of what ecosystem processes are operating in the watershed and how they have been affected by outside variables. A watershed-based analysis template developed in the Pacific Northwest can be a valuable aid in developing that level of understanding. The watershed analysis technique identifies four ecosystem scales useful to identify stream restoration priorities: region, basin, watershed, and site. The watershed analysis technique is based on a set of technically rigorous and defensible procedures designed to provide information on what processes are active at the watershed scale, how those processes are distributed in time and space. They help describe what the current upland and riparian conditions of the watershed are and how these conditions in turn influence aquatic habitat and other beneficial uses. The analysis is organized as a set of six steps that direct an interdisciplinary team of specialists to examine the biotic and abiotic processes influencing aquatic habitat and species abundance. This process helps develop an understanding of the watershed within the context of the larger ecosystem. The understanding gained can then be used to identify and prioritize aquatic restoration activities at the appropriate temporal and spatial scale. The watershed approach prevents relying solely on site-level information, a common problem with historic restoration efforts. When the watershed analysis process was used in the Whitefish Mountains of northwest Montana, natural resource professionals were able to determine the dominant habitat forming processes important for native fishes and use that information to prioritize, plan, and implement the appropriate restoration activities at the watershed scale. Despite considerable investments of time and resources needed to complete an analysis at the watershed scale, the results can prevent the misdiagnosis of aquatic problems and help ensure that the objectives of aquatic restoration will be met.

An adult case of acute biphenotypic leukemia with characteristic mixed morphology.

A case of acute biphenotypic leukemia with mixed blast morphology and combined myeloid and T-lymphoid features is reported. The leukemic cells consisted of small lymphoid hand-mirror blasts and large blasts with cytoplasmic granules and rare Auer rods. The cells expressed myeloid and immature T-lymphoid features by cytochemistry and immunophenotyping, however T cell receptor genes were in germline configuration. Cases of biphenotypic leukemia with similar morphological and immunophenotypic findings have been described previously in children. This case represents a morphologically and phenotypically distinct subtype of acute biphenotypic leukemia.