Biology and Clinical Implications of Fecal Occult Blood Test Screen-Detected Colorectal Cancer.

Background: Fecal occult blood test (FOBT)-based screening for colorectal cancer (CRC) reduces mortality, with earlier stage at diagnosis a prominent feature. Other characteristics of FOBT screen-detected cancers and any implications for clinical management have not been well explored.

Methods: We examined a multisite clinical registry to compare the characteristics and outcomes of FOBT screen-detected CRC via the Australian National Bowel Cancer Screening Program (NBCSP), which is offered biennially to individuals aged 50-74 years, and age-matched non-screen-detected CRC in the same registry.

Outcomes of perineal reconstruction with inferior gluteal artery myocutaneous flaps and primary closure following abdominoperineal resection.

Background: Perineal wound morbidity following abdominoperineal resection (APR) is a significant challenge. Myocutaneous flap-based techniques have been developed to overcome morbidity associated with perineal reconstruction. We reviewed outcomes for patients undergoing APR in a hospital that performs inferior gluteal artery myocutaneous (IGAM) island transposition flaps and primary closure (PC) for perineal reconstruction.

Entropy-regularized deconvolution of cellular cryotransmission electron tomograms.

Cryo-electron tomography (cryo-ET) allows for the high-resolution visualization of biological macromolecules. However, the technique is limited by a low signal-to-noise ratio (SNR) and variance in contrast at different frequencies, as well as reduced Z resolution. Here, we applied entropy-regularized deconvolution (ER-DC) to cryo-ET data generated from transmission electron microscopy (TEM) and reconstructed using weighted back projection (WBP).

Stage dependent recurrence patterns and post-recurrence outcomes in non-metastatic colon cancer.

Background: Multiple meta-analyses have demonstrated that routine surveillance following colorectal cancer surgery improves survival outcomes. There is limited data on how recurrence patterns and post-recurrence outcomes vary by individual tumor stage.

Methods: Using a multi-site community cohort study, we examined the potential impact of primary tumor stage on the sites of recurrence, management of recurrent disease with curative intent, and post-resection survival.

Positive lateral pelvic lymph nodes in low rectal cancer: should we change our practice now?

Background: The role of lateral lymph node dissection (LLND) in the treatment of patients with low rectal cancer with enlarged lateral lymph nodes (LLN+) is under investigation. Enthusiasm for LLND stems from a perceived reduction in local recurrence (LR). We aimed to compare the LR rate for LLN+ patients with LLN- patients, treated with neoadjuvant chemoradiotherapy (nCRT) and surgery, in a hospital that does not perform LLND.

Real-world outcomes for neoadjuvant capecitabine versus infusional 5-fluorouracil in the treatment of locally advanced rectal cancer.

Background: Neoadjuvant chemoradiation therapy is standard-of-care treatment for locally advanced rectal cancer (LARC). A pathological complete response (pCR) following chemoradiation therapy is an early indicator of treatment benefit and associated with excellent survival outcomes, with capecitabine largely replacing infusional 5-fluorouracil as the choice in routine care of LARC.

Aims: To analyse the uptake of capecitabine usage over time, and on the back of clinical trial data demonstrating equivalence between fluoropyrimidines, confirm that efficacy is maintained in the real-world setting.

Evaluation of the transferability of survival calculators for stage II/III colon cancer across healthcare systems.

Adjuvant! Online Inc (A!O), the Memorial Sloan Kettering Cancer Center (MSKCC), MD Anderson (MDA) and Mayo Clinic (MC) provide calculators to predict survival probabilities for patients with resected early-stage colon cancer, trained on data from United States (US) patient cohorts or patients enrolled in international clinical trials. Limited data exist on the transferability of calculators across healthcare systems. Calculator transferability to Australian community practice was evaluated for 1,401 stage II/III patients.

Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study.

Objective: For patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC.

Design: We enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy.

Super-Selective Mesenteric Embolization Provides Effective Control of Lower GI Bleeding.

. We aimed to assess the efficacy and safety of digital subtraction angiography (DSA) and super-selective mesenteric artery embolization (SMAE) in managing lower GI bleeding (LGIB). .

Msa1 and Msa2 Modulate G1-Specific Transcription to Promote G1 Arrest and the Transition to Quiescence in Budding Yeast.

Yeast that naturally exhaust their glucose source can enter a quiescent state that is characterized by reduced cell size, and high cell density, stress tolerance and longevity. The transition to quiescence involves highly asymmetric cell divisions, dramatic reprogramming of transcription and global changes in chromatin structure and chromosome topology. Cells enter quiescence from G1 and we find that there is a positive correlation between the length of G1 and the yield of quiescent cells.

Relative telomere lengths in tumor and normal mucosa are related to disease progression and chromosome instability profiles in colorectal cancer.

Telomeric dysfunction is linked to colorectal cancer (CRC) initiation. However, the relationship of normal tissue and tumor telomere lengths with CRC progression, molecular features and prognosis is unclear. Here, we measured relative telomere length (RTL) by real-time quantitative PCR in 90 adenomas (aRTL), 419 stage I-IV CRCs (cRTL) and adjacent normal mucosa (nRTL).

Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair-Proficient Stage II Colon Cancer.

Purpose: Prognostic markers that identify patients with stage II colon cancers who are at the risk of recurrence are essential to personalize therapy. We evaluated the potential of GIV/Girdin as a predictor of recurrence risk in such patients.

Experimental Design: Expression of full-length GIV was evaluated by IHC using a newly developed mAb together with a mismatch repair (MMR)-specific antibody panel in three stage II colon cancer patient cohorts, that is, a training (n = 192), test (n = 317), and validation (n = 181) cohort, with clinical follow-up data.

Primary Tumor Resection and Overall Survival in Patients With Metastatic Colorectal Cancer Treated With Palliative Intent.

Background: The survival impact of primary tumor resection in patients with metastatic colorectal cancer (mCRC) treated with palliative intent remains uncertain. In the absence of randomized data, the objectives of the present study were to examine the effect of primary tumor resection (PTR) and major prognostic variables on overall survival (OS) of patients with de novo mCRC.

Patients And Methods: Consecutive patients from the Australian 'Treatment of Recurrent and Advanced Colorectal Cancer' registry were examined from June 2009 to March 2015.

Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria.

In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database.

Primary Tumor Resection in Patients With Metastatic Colorectal Cancer Is Associated With Reversal of Systemic Inflammation and Improved Survival.

Background: The true survival benefit of noncurative primary tumor resection in patients with de novo metastatic colorectal cancer (mCRC) remains uncertain. The present study examined the effect of primary tumor resection on systemic inflammation and survival in patients with mCRC.

Materials And Methods: Consecutive patients with de novo mCRC who had undergone primary tumor resection were identified from a prospective database.

Reconstruction of the irradiated extended abdominoperineal excision (APE) defect for locally advanced colorectal cancer.

Purpose: There is substantial evidence for neoadjuvant chemoradiotherapy and extended abdominoperineal excision (APE) for improving local recurrence rates and overall survival for rectal carcinoma. While oncologic outcomes are improved, the large irradiated defect in the pelvic floor can potentiate poor operative outcomes. We describe a reconstructive option, the inferior gluteal artery myocutaneous (IGAM) transposition flap, which can enable wide tumour resections by providing substantial non-irradiated tissue bulk.

Risk factors for colonic perforation after screening computed tomographic colonography: a multicentre analysis and review of the literature.

Background: Computed tomographic (CT) colonography (or 'virtual' colonoscopy) has become an increasingly popular tool for colorectal cancer screening. Colonic perforation, an uncommon complication, is a risk that has not been widely reported.

Methods: A systematic review of the literature was undertaken to identify all reported risk factors for colonic perforation following CT colonography.

Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF(V600E) mutation.

BRAF(V600E) mutations are found in 10% of colorectal cancers (CRCs). The low frequency of this mutation therefore makes it a challenging target for drug development, unless subsets of patients with higher rates of BRAF(V600E) can be defined. Knowledge of the concordance between primary-metastasis pairs and the impact of BRAF(V600E) on outcome would also assist in optimal drug development.

Inferior gluteal artery myocutaneous island transposition flap reconstruction of irradiated perineal defects.

Background: With the progressive use of more radical surgical resections and pre-operative chemo-radiotherapy for locally advanced anorectal cancers, there has become an increasing need for reconstructive options that import well-vascularised tissue of sufficient bulk to the perineum. We present our technique of inferior gluteal artery myocutaneous (IGAM) transposition flaps for reconstruction after extended abdomino-perineal excision (APE) for anorectal cancer.

Methods: Six consecutive male patients with T2/T3 rectal carcinoma underwent neoadjuvant chemo-radiotherapy followed by extended APE and immediate reconstruction with an islanded IGAM transposition flap.