The Methods of Reconstruction of Pancreatic Digestive Continuity After Pancreaticoduodenectomy: A Meta-Analysis of Randomized Controlled Trials

Background  

Pancreatic fistula (PF) is an important factor responsible for the considerable morbidity associated with pancreaticoduodenectomy (PD). There have been many techniques proposed for the reconstruction of pancreatic digestive continuity to prevent fistula formation but which is best is still highly debated. We carried out a systematic review and meta-analysis to determine the effectiveness of methods of anastomosis after PD.     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone

Treatment with isolated allogeneic mesenchymal cells has the potential to enhance the therapeutic effects of conventional bone marrow transplantation in patients with genetic disorders affecting mesenchymal tissues, including bone, cartilage, and muscle. To demonstrate the feasibility of mesenchymal cell therapy and to gain insight into the transplant biology of these cells, we used gene-marked, donor marrow-derived mesenchymal cells to treat six children who had undergone standard bone marrow transplantation for severe osteogenesis imperfecta. Each child received two infusions of the allogeneic cells. Five of six patients showed engraftment in one or more sites, including bone, skin, and marrow stroma, and had an acceleration of growth velocity during the first 6 mo postinfusion. This improvement ranged from 60% to 94% (median, 70%) of the predicted median values for age- and sex-matched unaffected children, compared with 0% to 40% (median, 20%) over the 6 mo immediately preceding the infusions. There was no clinically significant toxicity except for an urticarial rash in one patient just after the second infusion. Failure to detect engraftment of cells expressing the neomycin phosphotransferase marker gene suggested the potential for immune attack against therapeutic cells expressing a foreign protein. Thus, allogeneic mesenchymal cells offer feasible posttransplantation therapy for osteogenesis imperfecta and likely other disorders originating in mesenchymal precursors.     

Second‐look endoscopy with thermal coagulation or injections for peptic ulcer bleeding: A meta‐analysis

Background and Aims: In the management of peptic ulcer bleeding, the benefits of second‐look endoscopic treatment with thermal coagulation or injections in controlling recurrent bleeding is unsure. This study set out to compare efficacy of routine second‐look endoscopy with treatment using either thermal coagulation or injections versus single endoscopy by pooling data from published work. Methods: Full publications in the English‐language published work as well as abstracts in major international conferences were searched over the past 10 years, and six trials fulfilling the search criteria were found. Outcome measurements included: (i) recurrent bleeding; (ii) requirement of surgical intervention; and (iii) mortality. We examined heterogeneity of trials and pooled the effects by meta‐analysis. The quality of studies was graded according to the prospective randomization, methods of patient allocation, the list of exclusion criteria, outcome definitions and the predefined salvage procedures for uncontrolled bleeding. Results: Among 998 patients recruited in these five randomized trials, 119 received routine second‐look endoscopy with thermal coagulation, and 374 received second‐look with endoscopic injection and 505 had single endoscopic therapy. Less recurrent bleeding was reported after thermal coagulation (4.2%) than single endoscopy (15.7%) (relative risk [RR] = 0.29; 95% confidence interval [CI] = 0.11–0.73), but no reduction was reported for the requirement of surgical intervention and all‐cause mortality. Injection therapy did not reduce re‐bleeding (17.6%) when compared to single endoscopy (20.8%; RR = 0.85; 95% CI = 0.63–1.14), requirement for surgery and mortality. Conclusion: Routine second‐look endoscopy with thermal coagulation, but not injection therapy, reduced recurrent peptic ulcer bleeding. There is no proven benefit in reducing surgical intervention and overall mortality.     

Is there still a role for aprotinin in cardiac surgery?

Cardiac surgery is associated with a systemic inflammatory response and systemic coagulopathy, which can result in significant organ dysfunction and bleeding. Aprotinin, a serine protease inhibitor, can limit systemic inflammation, and has been associated with myocardial, pulmonary and cerebral protection in addition to its proven haemostatic efficacy. Data are currently conflicting regarding the haemostatic efficacy of aprotinin relative to alternative agents including tranexamic acid. Recent studies have demonstrated aprotinin usage is associated with increased rates of thrombotic and renal complications, but these findings are at odds with the majority of studies relating to aprotinin safety to date. The lack of adequately powered, randomised studies evaluating aprotinin and alternative agents limits drawing conclusions about the complete use or disuse of aprotinin presently and requires individualised patient selection based on bleeding risk and co-morbidities for its usage.     

A new assay to assess steroid-hormone responsiveness in head and neck cancer

A new assay has been developed to predict the effectiveness of steroid-hormone therapy in various tumors. The Biopsy Nuclear Binding assay measures the amount of biologically active receptor that binds both steroid hormone and acceptor sites in the nucleus. This assay does not measure the entire receptor population, only those that are biologically active; therefore, it should more accurately predict the response to steroid-hormone therapy. We applied this assay effectively in breast and endometrial carcinoma. Preliminary studies have shown that 40% of patients with head and neck squamous-cell carcinomas have biologically active (nuclear bound) progesterone receptors. If nuclear binding predicts a remission with hormonal therapy, then the quality of life of appropriately selected patients could greatly improve.     

The docking protein Gab2 is overexpressed and estrogen regulated in human breast cancer

Grb2-associated binder 2 (Gab2) is a recently identified member of the Gab/Daughter of sevenless family of docking proteins, which localize, amplify and integrate signaling pathways activated by various receptors including receptor tyrosine kinases (RTKs). To date, Gab2 signaling has been primarily investigated in hematopoietic cells. Here we report marked overexpression of Gab2 in a subset of breast cancer cell lines relative to normal breast epithelial strains and a trend for increased Gab2 expression in estrogen receptor (ER)-positive lines. Overexpression relative to normal ductal epithelium was also observed in some primary breast cancers. In MCF-7 breast cancer cells Gab2 was markedly tyrosine phosphorylated in response to heregulin and also following EGF, insulin or bFGF administration, indicating that a variety of RTKs implicated in breast cancer development or progression couple to this docking protein. In hormone-responsive breast cancer cells, GAB2 mRNA and protein expression were induced by estradiol in a manner sensitive to the pure anti-estrogen ICI 182780, indicating that this regulation is mediated via the ER. Gab2 therefore represents a novel link between steroid and growth factor signaling in breast cancer, and when overexpressed, may modulate the sensitivity of breast cancer cells to these important growth regulators.     

Posttraumatic stress symptomatology and cancer

The extant nosological formulations of the American Psychiatric Association denotes that Posttraumatic Stress Disorder (PTSD) maybe predicated upon some life threatening experience. Historically, combat, robbery, rape, and serious accidents have been included as traumatogenetic stressors. Only recently has life-threatening illness been considered as a traumatogenetic stressor. This paper reviews the relativity between cancer and posttraumatic stress.