Distinct risk factors for early and late blood transfusion following pancreaticoduodenectomy.

BACKGROUND: The International Study Group of Pancreatic Surgery (ISGPS) has defined two periods of postpancreatectomy hemorrhage, early (<24 h) and late (>24 h). A previously published Blood Usage Risk Score (BURS) aimed to predict early and late blood transfusion. The primary aim of this study was to define risk factors for early and late blood transfusion after pancreaticoduodenectomy. Secondary aims were to assess the predictive accuracy of the BURS. METHODS: In this retrospective observational study, multivariable analyses were used to identify independent risk factors for both early and late blood transfusion. The predictive ability of the BURS was then assessed using a receiver operating characteristic (ROC) curve analysis. RESULTS: Among 628 patients, 99 (15.8%) and 144 (22.9%) received early and late blood transfusion, respectively. Risk factors for blood transfusion differed between early and late periods. Preoperative anemia and venous resection were associated with early blood transfusion whilst Whipple's resection (as opposed to pylorus preserving pancreaticoduodenectomy), lack of biliary stent and a narrow pancreatic duct were predictors of late blood transfusion. The BURS was significantly predictive of early blood transfusion, albeit with a modest degree of accuracy (AUROC: 0.700, P < 0.001), but not of late blood transfusion (AUROC: 0.525, P = 0.360). Late blood transfusion was independently associated with increasing severity of postoperative pancreatic fistula (POPF) (OR: 1.85, 3.18 and 9.97 for biochemical, types B and C POPF, respectively, relative to no POPF). CONCLUSIONS: Two largely different sets of variables are related to early and late blood transfusion following pancreaticoduodenectomy. The BURS was significantly associated with early, albeit with modest predictive accuracy, but not late blood transfusion. An understanding of POPF risk allows assessment of the need for late blood transfusion.

Does blood group affect survival following pancreatoduodenectomy for periampullary malignancy?

BACKGROUND: Blood group is reported to have an effect upon survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma. The effect of blood group is not known, however, among patients with other periampullary cancers. This study sought to review this. METHODS: Data were collected for a range of factors and survival outcomes from patients treated at two centres. Those with blood groups B and AB were excluded, due to small numbers. Patient survival was compared between patients with blood groups O and A using multivariable analysis which accounted for confounding factors. RESULTS: Among 431 patients, 235 (54.5%) and 196 (45.5%) were of blood groups A and O respectively. Baseline comparisons found a significant difference in the distribution of tumour types (p = 0.011), with blood group O patients having more ampullary carcinomas (33.2% vs 23.4%) and less pancreatic ductal adenocarcinomas (45.4 vs 61.3%) than group A. On multivariable analysis, after accounting for confounding factors including pathologic variables, survival was found to be significantly shorter in those with blood group A than group O (p = 0.047, HR 1.30 [95%CI: 1.00-1.69]). CONCLUSIONS: There is a difference in the distribution of blood groups across the different types of periampullary cancers. Survival is shorter among blood group A patients.

Cost analysis of open radical cystectomy versus robot-assisted radical cystectomy.

OBJECTIVES: To perform a cost analysis comparing the cost of robot-assisted radical cystectomy (RARC) with open RC (ORC) in a UK tertiary referral centre and to identify the key cost drivers. PATIENTS AND METHODS: Data on hospital length of stay (LOS), operative time (OT), transfusion rate, and volume and complication rate were obtained from a prospectively updated institutional database for patients undergoing RARC or ORC. A cost decision tree model was created. Sensitivity analysis was performed to find key drivers of overall cost and to find breakeven points with ORC. Monte Carlo analysis was performed to quantify the variability in the dataset. RESULTS: One RARC procedure costs £12 449.87, or £12 106.12 if the robot was donated via charitable funds. In comparison, one ORC procedure costs £10 474.54. RARC is 18.9% more expensive than ORC. The key cost drivers were OT, LOS, and the number of cases performed per annum. CONCLUSION: High ongoing equipment costs remain a large barrier to the cost of RARC falling. However, minimal improvements in patient quality of life would be required to offset this difference.

Pro-invasive Effect of Proto-oncogene PBF Is Modulated by an Interaction with Cortactin.

CONTEXT: Metastatic disease is responsible for the majority of endocrine cancer deaths. New therapeutic targets are urgently needed to improve patient survival rates. OBJECTIVE: The proto-oncogene PTTG1-binding factor (PBF/PTTG1IP) is overexpressed in multiple endocrine cancers and circumstantially associated with tumor aggressiveness. This study aimed to understand the role of PBF in tumor cell invasion and identify possible routes to inhibit its action. Design, Setting, Patients, and Interventions: Thyroid, breast, and colorectal cells were transfected with PBF and cultured for in vitro analysis. PBF and cortactin (CTTN) expression was determined in differentiated thyroid cancer and The Cancer Genome Atlas RNA-seq data. PRIMARY OUTCOME MEASURE: Pro-invasive effects of PBF were evaluated by 2D Boyden chamber, 3D organotypic, and proximity ligation assays. RESULTS: Our study identified that PBF and CTTN physically interact and co-localize, and that this occurs at the cell periphery, particularly at the leading edge of migrating cancer cells. Critically, PBF induces potent cellular invasion and migration in thyroid and breast cancer cells, which is entirely abrogated in the absence of CTTN. Importantly, we found that CTTN is over-expressed in differentiated thyroid cancer, particularly in patients with regional lymph node metastasis, which significantly correlates with elevated PBF expression. Mutation of PBF (Y174A) or pharmacological intervention modulates the PBF: CTTN interaction and attenuates the invasive properties of cancer cells. CONCLUSION: Our results demonstrate a unique role for PBF in regulating CTTN function to promote endocrine cell invasion and migration, as well as identify a new targetable interaction to block tumor cell movement.

The proto-oncogene PBF binds p53 and is associated with prognostic features in colorectal cancer.

The PTTG1-binding factor (PBF) is a transforming gene capable of eliciting tumor formation in xenograft models. However, the precise role of PBF in tumorigenesis and its prognostic value as a cancer biomarker remain largely uncharacterised, particularly in malignancies outside the thyroid. Here, we provide the first evidence that PBF represents a promising prognostic marker in colorectal cancer. Examination of a total of 39 patients demonstrated higher PBF expression at both the mRNA (P = 0.009) and protein (P < 0.0001) level in colorectal tumors compared to matched normal tissue. Critically, PBF was most abundant in colorectal tumors associated with Extramural Vascular Invasion (EMVI), increased genetic instability (GI) and somatic TP53 mutations, all features linked with recurrence and poorer patient survival. We further demonstrate by glutathione-S-transferase (GST) pull-down and coimmunoprecipitation that PBF binds to the tumor suppressor protein p53, as well as to p53 mutants (Δ126-132, M133K, V197E, G245D, I255F and R273C) identified in the colorectal tumors. Importantly, overexpression of PBF in colorectal HCT116 cells interfered with the transcriptional activity of p53-responsive genes such as mdm2, p21 and sfn. Diminished p53 stability (> 90%; P < 0.01) was also evident with a concurrent increase in ubiquitinated p53. Human colorectal tumors with wild-type TP53 and high PBF expression also had low p53 protein levels (P < 0.05), further emphasizing a putative interaction between these genes in vivo. Overall, these results demonstrate an emerging role for PBF in colorectal tumorigenesis through regulating p53 activity, with implications for PBF as a prognostic indicator for invasive tumors.