Conversion to Complete Resection and/or Ablation Using Hepatic Artery Infusional Chemotherapy in Patients with Unresectable Liver Metastases from Colorectal Cancer: A Decade of Experience at a Single Institution

Background

When feasible, surgical treatment of colorectal liver metastases (CRLM) is the treatment of choice. Regional hepatic artery infusional (HAI) chemotherapy effectively treats CRLM. The combination of HAI and systemic chemotherapy may downsize tumors and allow for complete resection and/or ablation (R/A). This study analyzes the combination of HAI and systemic chemotherapy for treating unresectable CRLM, focusing on conversion to complete R/A.

Methods

All patients with unresectable CRLM treated with HAI and systemic chemotherapy from 2000 to 2009 were included. Patients who responded sufficiently to undergo complete R/A were compared to those who did not convert. Survival was compared using a landmark analysis to account for bias.

Results

A total of 373 patients were included; 93 patients (25 %) subsequently underwent complete R/A. The percentage of patients submitted to complete R/A increased from 16 % during 2000–2003 to 30 % during 2004–2009. Factors associated with conversion on multivariate analysis were more recent treatment (2004–2009), no prior chemotherapy, clinical risk score <3, treatment on clinical protocol, and younger age. Median and predicted 5-year survival from the time of HAI pump placement was 59 months and 47 %, respectively, in the patients who converted to complete R/A, compared with 16 months and 6 %, respectively in those who did not (p < 0.001).

Conclusions

Despite extensive disease, 25 % of patients with unresectable CRLM responded sufficiently to undergo complete R/A following HAI plus systemic chemotherapy. Combination HAI and systemic chemotherapy is an effective strategy to convert patients to complete resection with an associated excellent long-term survival.     

Effects of Kinesio Taping on postural balance in patients with low back pain,a randomized controlled trial

Purpose: to identify postural balance changes in subjects with low back pain after the application of Kinesio Taping, which is then compared to a no treatment control group, using baropodometric evaluation. Methods: This randomized controlled trial was carried out on 50 individuals (both sexes) with chronic low back pain. They were then randomized into two groups: an experimental group - EG (treated with Kinesio Taping in the lumbar region) and a control group - CG (no intervention). Both groups underwent a baropodometric evaluation (mean plantar pressure, peak plantar pressure, plantar surface, mass distribution on right foot and left foot, mass distribution on forefoot and rear foot and base width) at four different moments: pre-intervention, 10 minutes, 48 hours, and 10 days after the intervention on the EG. The level of statistical significance was established at 5%. Results: Significant changes were observed in the EG compared to the CG. In the EG, peak pressure reduced on both right and left foot after Kinesio Taping application; the right base width was reduced, and the mass distribution between the forefoot and the rear foot normalized towards the ideal 50% distribution. These changes happened 48 hours after the Kinesio Taping application, with effects lasting up to 10 days. Conclusion: The use of Kinesio Taping in the lumbar region of subjects with chronic low back pain improved postural balance. This is proved by changes in peak plantar pressure, plantar surface, and mass distribution 48 h after Kinesio Taping application, with effects lasting up to 10 days.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

A perioperative multidisciplinary care bundle reduces surgical site infections in patients undergoing synchronous colorectal and liver resection

Background

Surgical site infections (SSIs) are a major cause of morbidity, mortality, and healthcare costs, and patients undergoing simultaneous colorectal/liver resections are at an especially high SSI risk.

Natural killer (NK) cells in chronic progressive multiple sclerosis patients treated with lymphoblastoid interferon

Natural killer (NK) cell functional activity, as defined by the lysis of 51Cr-labelled K-562 cells, and number, defined phenotypically by anti-Leu-11, are significantly decreased in chronic progressive multiple sclerosis (MS) when compared to normal controls. When age- and sex-matched populations are compared, NK cell functional activity is again significantly reduced in MS compared to controls but not when compared to a control group of other medical disease (OMD). The MS group could be differentiated from the OMD group, however, when results of NK cell functional activity are combined with NK cell phenotype. With the administration of lymphoblastoid interferon daily for 6 months, NK cell activity increased significantly at 48 h and at 1 week. By 1 month, activity decreased to a level slightly above placebo treatment values. The results likely reflect interferon's enhancement of mature NK cell activity combined with a variable effect on recruitment of pre-NK cells.     

Composite sequential arterial reconstruction for limb salvage

OBJECTIVE: Autogenous vein is the conduit of choice in patients presenting for infrainguinal arterial reconstruction. Venous conduit may be limited because of inadequacy or prior utilization. Our group and others use prosthetics to maximize limb salvage with moderate results. However, in cases where patients present with an isolated popliteal segment that may extend below the knee, we have performed prosthetic bypasses to this above-knee segment and then used a venous reconstruction from the native arterial circulation to a more distal outflow tract. In this report, we will analyze our results using this type of reconstruction in patients who present for limb salvage with no all-autogenous option. METHOD: From 1992 to 2000, 27 patients presented for limb salvage with an isolated popliteal artery and inadequate vein for continuous bypass. There were 106 patients in this period without an isolated popliteal segment or adequate vein who underwent prosthetic bypass with distal vein cuff or arteriovenous fistula. The vascular registry and patient charts were reviewed for indication, demographics, and type of composite reconstruction. Outcomes were calculated with use of life table methods and compared by log rank analysis. RESULTS: Demographics revealed 16 (59%) men, 16 (59%) patients with diabetes, and 4 (15%) smokers with a mean age of 71 years (range, 51-87 years). The venous reconstructions had the inflow taken from the distal native popliteal artery in 26 (above knee in 8 and below knee in 18) and the peroneal artery in one. The outflow involved the below-knee popliteal in one (4%), a tibial in 23 (85%), and the dorsalis pedis artery in 3 (11%). Morbidity included bleeding (4%), wound infection (4%), and limb loss (4%). Mortality occurred in one patient (4%), and no revisions were required in follow-up. Six late failures were identified, one of which resulted in amputation. Primary patency and limb salvage were 80% and 88% at 1 year, respectively. For comparison, our results using prosthetic with vein cuff had a 1-year primary patency of 52% and limb salvage of 92% (P = NS), whereas prosthetic with an arteriovenous fistula was 73% and 84%, respectively (P = NS). CONCLUSIONS: Composite sequential reconstruction using an isolated popliteal segment as inflow for the distal reconstruction is an acceptable option in patients presenting for limb salvage reconstruction with limited venous conduit. This type of reconstruction, when available, may be a better option than pure prosthetic with or without a vein cuff or arteriovenous fistula.     

Risks and side effects of islet transplantation

Islet transplantation can deliver stable glycemic control, relief from recurrent severe hypoglycemia, and insulin independence. Accessing the portal vein via the percutaneous hepatic approach carries the risk of bleeding, and the infusion of islets a risk of portal vein thrombosis. In the long term, common minor problems with immunosuppression are mouth ulcers, diarrhea, and acne. Longer-term risks include malignancy and serious infection, both rare to date in clinical islet transplantation. Sensitization to donor antigens may also occur. The long-term diabetes complications may stabilize, but of this aspect little is known to date. In the short term, there may be some elevation of serum cholesterol and blood pressure, in some patients there has been a decline in renal function, and in a few, acute retinal bleeds. For most, improvement in glucose control with resolution of glycemic lability and hypoglycemia has been a net benefit.     

The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis versus proliferation

Mutation, deactivation and disregulated expression of oncogenes and tumour-suppressor genes may be involved in the pathogenesis of oral squamous cell carcinoma (SCC). Deactivation of the p53 tumour-suppressor gene allows cell proliferation and blocks apoptosis of malignant oral keratinocytes. Mutation in the ras oncog-ene results in persistent mitogenic signalling. Upregul-ated c-Myc expression, in the presence of growth factors, provides an additional proliferative signal. Loss of retino-blastoma tumour-suppressor gene (Rb) function may contribute to oral keratinocyte hyperproliferation and recent evidence suggests that simultaneous deactivation of both p53 and Rb is required for tumourigenesis. Enhanced Bcl-2 and reduced Fas expression inhibit tumour cell apoptosis and may convey resistance to cyto-toxic drugs and T cell-mediated cytotoxicity, respectively. Exogenous mutagens such as tobacco, alcohol and viral oncogenes may cause altered expression of oncogenes and tumour-suppressor genes in some cases of oral SCC. The impact of these mechanisms on future therapies for oral SCC is highlighted.     

CardioDiabetes: Core Competencies for Cardiovascular Clinicians in a Rapidly Evolving Era of Type 2 Diabetes Management

A sea change in the management of diabetes is occurring with the publication of clinical trials showing unequivocal cardiovascular (CV) protection through the use of certain antihyperglycemic agents. This change is similar to the change that occurred when lipid lowering with statins was first shown to have CV benefits, an event necessitating changes in training and the proactive treatment of lipids by CV specialists. As was the case then, many CV specialists currently feel poorly equipped to address diabetes with this new information even though diabetes is common in CV practice. The purpose of this overview is to provide an updated, comprehensive, and evidence-based CV protection plan for patients with type 2 diabetes, intended specifically for cardiologists and vascular medicine specialists. We attempt to elucidate a set of “CardioDiabetes” core competencies by merging the CV-relevant elements of the Diabetes Canada 2018 guidelines within a framework of comprehensive vascular protection as supported by other CV guidelines. We review the rationale for measuring hemoglobin A1C, understanding its use for establishing a diagnosis and for monitoring treatment. We also provide a brief review of the medications most important for a CV specialist to know. We provide useful memory aids and a succinct set of reminders and tips (“ABCDEFR’S”) that can serve as a comprehensive checklist in the clinic and help to motivate trainees and clinicians to consult the original guideline source documents to enrich their knowledge and improve treatment in this rapidly changing arena.