A Systematic Review of Minimally Invasive Trans-thoracic Liver Resection to Examine Intervention Description, Governance, and Outcome Reporting of an Innovative Technique.

INTRODUCTION: The number of laparoscopic liver resections undertaken has increased. However, lesions located postero-superiorly are difficult to access. This may be overcome by the novel use of trans-thoracic port(s). Methods for the safe and transparent introduction of new and modified surgical procedures are limited and a summary of these issues, for minimally invasive trans-thoracic liver resections (MITTLR), is lacking. This study aims to understand and summarize technique description, governance procedures, and reporting of outcomes for MITTLR. METHODS: A systematic literature search to identify primary studies of all designs describing MITTLR was undertaken. How patients were selected for the new technique was examined. The technical components of MITTLR were identified and summarized to understand technique development over time. Governance arrangements (eg, Institutional Review Board approval) and steps taken to mitigate harm were recorded. Finally, specific outcomes reported across studies were documented. RESULTS: Of 2067 screened articles, 16 were included reporting data from 145 patients and 6 countries. Selection criteria for patients was explicitly stated in 2 papers. No studies fully described the technique. Five papers reported ethical approval and 3 gave details of patient consent. No study reported on steps taken to mitigate harm.Technical outcomes were commonly reported, for example, blood loss (15/16 studies), operative time (15/16), and margin status (11/16). Information on patient-reported outcomes and costs were lacking. CONCLUSIONS: Technical details and governance procedures were poorly described. Outcomes focussed on short term details alone. Transparency is needed for reporting the introduction of new surgical techniques to allow their safe dissemination.

A 4-gene signature predicts survival of patients with resected adenocarcinoma of the esophagus, junction, and gastric cardia.

BACKGROUND & AIMS: The incidence of esophageal and junctional adenocarcinoma has increased 6-fold in the past 30 years and 5-year survival remains approximately 20%. Current staging is limited in its ability to predict survival which has ramifications for treatment choices. The aim of this study was to generate and validate a molecular prognostic signature for esophageal adenocarcinoma. METHODS: Gene expression profiling was performed and the resulting 42,000 gene signatures correlated with clinical and pathologic features for 75 snap-frozen esophageal and junctional resection specimens. External validation of selected targets was performed on 371 independent cases using immunohistochemistry to maximize clinical applicability. RESULTS: A total of 119 genes were associated significantly with survival and 270 genes with the number of involved lymph nodes. Filtering of these lists resulted in a shortlist of 10 genes taken forward to validation. Four genes proved to be prognostic at the protein level (deoxycytidine kinase [DCK], 3'-phosphoadenosine 5'-phosphosulfate synthase 2 [PAPSS2], sirtuin 2 [SIRT2], and tripartite motif-containing 44 [TRIM44]) and were combined to create a molecular prognostic signature. This 4-gene signature was highly predictive of survival in the independent external validation cohort (0/4 genes dysregulated 5-year survival, 58%; 95% confidence interval [CI], 36%-80%; 1-2/4 genes dysregulated 5-year survival, 26%; 95% CI, 20%-32%; and 3-4/4 genes dysregulated 5-year survival, 14%; 95% CI, 4%-24% (P = .001). Furthermore, this 4-gene signature was independently prognostic in a multivariable model together with the existing clinical TNM staging system (P = .013). CONCLUSIONS: This study has generated a clinically applicable prognostic gene signature that independently predicts survival in an external validation cohort and may inform management decisions.

Massive urinary ascites after removal of a supra-pubic catheter: case report and review of the literature.

Urinary ascites is a rare diagnosis usually associated with intra-peritoneal bladder perforation. We present a case of massive urinary ascites in a patient who presented 1 week after a total abdominal hysterectomy and sacrocolpopexy. We discuss how the diagnosis was made, the mechanism of biochemical changes associated with urinary ascites and the management. In summary, we show that a combination of serum and ascitic biochemistry are essential to make a diagnosis of urinary ascites.

Selective loss of TGFbeta Smad-dependent signalling prevents cell cycle arrest and promotes invasion in oesophageal adenocarcinoma cell lines.

In cancer, Transforming Growth Factor beta (TGFbeta) increases proliferation and promotes invasion via selective loss of signalling pathways. Oesophageal adenocarcinoma arises from Barrett's oesophagus, progresses rapidly and is usually fatal. The contribution of perturbed TGFbeta signalling in the promotion of metastasis in this disease has not been elucidated. We therefore investigated the role of TGFbeta in Barrett's associated oesophageal adenocarcinoma using a panel of cell lines (OE33, TE7, SEG, BIC, FLO). 4/5 adenocarcinoma cell lines failed to cell cycle arrest, down-regulate c-Myc or induce p21 in response to TGFbeta, and modulation of a Smad3/4 specific promoter was inhibited. These hyperproliferative adenocarcinoma cell lines displayed a TGFbeta induced increase in the expression of the extracellular matrix degrading proteinases, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1), which correlated with an invasive cell phenotype as measured by in vitro migration, invasion and cell scattering assays. Inhibiting ERK and JNK pathways significantly reduced PAI and uPA induction and inhibited the invasive cell phenotype. These results suggest that TGFbeta Smad-dependent signalling is perturbed in Barrett's carcinogenesis, resulting in failure of growth-arrest. However, TGFbeta can promote PAI and uPA expression and invasion through MAPK pathways. These data would support a dual role for TGFbeta in oesophageal adenocarcinoma.

In vivo and in vitro evidence for transforming growth factor-beta1-mediated epithelial to mesenchymal transition in esophageal adenocarcinoma.

There is increasing evidence that epithelial to mesenchymal transition (EMT) is involved in cancer progression. Because local invasion and metastasis occurs early in the pathogenesis of esophageal adenocarcinoma, we hypothesized that EMT may be important in this disease. Using immunohistochemistry in a well-characterized set of adenocarcinoma tissues, we showed down-regulation of epithelial markers (E-cadherin and cytokeratin 18) and up-regulation of mesenchymal markers (vimentin and alpha-smooth muscle actin) with concomitant transforming growth factor-beta1 (TGF-beta1) expression at the invasive margin compared with the central tumor. A panel of esophageal cell lines was examined for the ability of TGF-beta1 to induce EMT in vitro. TE7 cells were selected as a model because TGF-beta1 (0-5 ng/mL) treatment induced morphologic and molecular expression changes suggestive of EMT. In TE7 cells, these TGF-beta1-induced changes were reversed by 100 ng/mL of bone morphogenetic protein 7 (BMP7), another member of the TGF-beta1 superfamily. EMT was mediated via canonical TGF-beta1 signaling with concomitant up-regulation of SMAD-interacting protein 1. Alterations in functional variables (aggregation, wounding, motility, and invasion) following TGF-beta1 treatment were consistent with a more invasive phenotype. These functional changes were reversed by BMP7 and SMAD4 RNA interference in vitro. These data suggest that TGF-beta1-mediated EMT may be relevant in esophageal carcinogenesis.