Benefits of resection for metachronous lung cancer

OBJECTIVES: The benefits of resection for metachronous lung cancer are not well described. The objective of this study was to evaluate the safety and efficacy of surgical resection for metachronous lung cancers. METHODS: We reviewed the charts of all patients who underwent a second resection for a metachronous lung cancer from July 1, 1988, to December 31, 2002. Type of resection, operative morbidity, mortality, and survival by stage were analyzed. Survival was determined by using the Kaplan-Meier survival method. All patients were pathologically staged by using the 1997 American Joint Committee on Cancer standards. RESULTS: Pulmonary resections were performed in 69 patients who had undergone a previous resection. The mean interval between the first and second resection was 2.4 +/- 2.5 years. Seventy-three percent of patients presented with stage I cancers, 9% with stage II cancers, and 17% with stage III cancers. Lobectomy and wedge resection were performed with equal frequency (42% each) for the metachronous cancers. Operative mortality for the second resection was 5.8%. The mean follow-up after the second resection was 37 months. Overall 5-year actuarial survival for the entire group after the second resection was 33.4%. CONCLUSIONS: Operations for metachronous cancers provided survival that approximated the expected survival for lung cancer. Surgical intervention should be considered as a safe and effective treatment for resectable metachronous lung cancer in patients with adequate physiologic pulmonary reserve.     

Hybrid coronary revascularization in the era of drug-eluting stents

Left internal mammary artery to left anterior descending coronary artery bypass grafting integrated with percutaneous coronary angioplasty (hybrid procedure) offers multivessel revascularization with minimal morbidity in high-risk patients. This is caused in part by the avoidance of cardiopulmonary bypass-related morbidity and manipulation of the aorta coupled with minimally invasive techniques. Hybrid revascularization is currently reserved for particularly high-risk patients or those with favorable anatomic variants however, largely because of the emergence of off-pump coronary artery bypass grafting, which permits more complete multivessel revascularization, with low morbidity in high-risk groups. The wider introduction of hybrid revascularization is limited chiefly by the high number of repeat interventions compared with off-pump coronary artery bypass grafting, which occurs because of the target vessel failure rate of percutaneous coronary intervention. Other demerits are the costs and logistic problems associated with performing two procedures with differing periprocedural management protocols. Recently, drug-eluting stents have reduced the need for repeat intervention after percutaneous coronary intervention, and this has raised the possibility that the results of hybrid revascularization may now equal or even better those of off-pump coronary artery bypass grafting. Although undoubtedly effective at reducing in-stent restenosis, drug-eluting stents will not address the issues of incomplete revascularization or the logistic problems associated with hybrid. Uncertainty regarding the long-term effectiveness of drug-eluting stents in many patients, as well as their high cost when compared with those of off-pump coronary artery bypass grafting surgery, also militates against the wider introduction of hybrid revascularization.     

Superior Long-Term Results of Simultaneous Pancreas–Kidney Transplantation from Pediatric Donors

The shortage of cadaveric donors for simultaneous pancreas-kidney transplantation has prompted the use of cadaveric organs from pediatric donors. The long-term outcome and its impact on overall long-term survival are unknown. A total of 680 recipients receiving cadaver Simultaneous pancreas-kidney (SPK) transplantation from pediatric and adult donors between July 1986 and September 2001 were analyzed and compared. Ten-year kidney and pancreas graft survival for SPK transplantation from donors aged <18 years (n = 142) were 80% and 72%, respectively, compared to 61% pancreas and kidney graft survival from donors > or =18 years of age (n = 538; p = 0.03 and 0.05, respectively). Five years post-transplant, blood glucose, HbA1c and creatinine clearance were significantly better in recipients from pediatric donors (85.3 +/- 13 mg/dL, 5.5 +/- 3.5% and 65.6 +/- 16 mL/min, respectively), compared to recipients from adult donors (95.1 +/- 29 mg/dL, 5.9 +/- 3.5% and 58.3 +/- 17 mL/min; p = 0.001, 0.01 and 0.002, respectively). Causes of graft failure for kidney and pancreas transplants were similar between the two groups. No statistically significant difference was observed in patient survival between recipients from pediatric donors compared to adult donors (85% vs. 76%, p = 0.29). When recipients of SPK from pediatric donors were stratified according to age (3-11 years and 12-17 years) and compared, no difference in kidney or pancreas graft survival was observed (kidney 76.4% vs. 81.3%, p = 0.15; pancreas 75% vs. 76%, p = 0.10, respectively). Pediatric donors represent a valuable source of organs, providing excellent short- and long-term outcomes. Wide utilization of pediatric organs will substantially increase the donor pool.     

Traumatic lumbar hernia: report of cases and comprehensive review of the literature

BACKGROUND: Acute lumbar hernia secondary to blunt trauma is an uncommon injury of the abdominal wall and, when encountered, is a difficult challenge for the trauma surgeon. METHODS: Three cases of lumbar hernia secondary to blunt trauma are described and a review of the literature was conducted for other such cases. Clinical, anatomic, and demographic data were extracted from these reports and analyzed. RESULTS: Sixty-three cases of lumbar hernia secondary to blunt trauma were found in the English literature and three cases are described here. Hernias occurred most commonly in the inferior lumbar triangle (70%) and were most frequently a result of a motor vehicle collision (71%). Physical examination findings were variable and reported in only a minority of cases (palpable hernia, 33%; flank hematoma, 27%) and associated intra-abdominal injuries were common (61%). Most traumatic lumbar hernias were diagnosed immediately, and computed tomography was 98% sensitive for diagnosis. Fifty-eight percent of patients were managed initially with exploratory laparotomy. Timing of hernia repair was variable. CONCLUSION: Traumatic lumbar hernias are associated with a high incidence of intra-abdominal injury and should be considered in all cases of severe blunt abdominal trauma. Computed tomography should be implemented when the diagnosis is suspected in a hemodynamically stable patient. Repair should be performed by mesh patching techniques at a time based on clinical correlation.     

Transverse Myelitis Secondary To Coexistent Lyme Disease And Babesiosis

Abstract

Objective: To describe transverse myelitis secondary to coexistent Lyme disease and babesiosis.

Method: Case report.

Background: A 7 4-year-old man presented with rapid onset of weakness, numbness, and tingling in his legs, with symptoms ascending to his hands and forearms within days. He recalled an insect bite to his scapular area 2 weeks earlier.

Findings: T2-weighted magnetic resonance imaging demonstrated diffuse hyperintensity from T1 through T1 2. Western blot and enzyme-linked immunosorbent assay identified infection with Borrelia burgdorferi, the spirochete responsible for Lyme disease. Giemsa-stained blood smears identified ring forms later recognized by polymerase chain reaction as Babesia microti, the piroplasm responsible for babesiosis. Initial examination revealed C7 motor and T3 sensory complete tetraplegia, with recovery to T 4 paraplegia by 2 months.

Conclusion: The history, physical examination, imaging, and serologic studies were consistent with transverse myelitis related to Lyme disease and babesiosis. The severity and permanence of this patient’s deficits were greater than those reported in the majority of previous cases of transverse myelitis due to Lyme disease alone, suggesting a possible role for coinfection with babesiosis.     

Worldwide variability in deceased organ donation registries

The variability in deceased organ donation registries worldwide has received little attention. We considered all operating registries, where individual wishes about organ donation were recorded in a computerized database. We included registries which recorded an individual's decision to be a donor (donor registry), and registries which only recorded an individual's objection (non-donor registry). We collected information on 15 characteristics including history, design, use and number of registrants for 27 registries (68%). Most registries are nationally operated and government-owned. Registrations in five nations expire and require renewal. Some registries provide the option to make specific organ selections in the donation decision. Just over half of donor registries provide legally binding authorization to donation. In all national donor registries, except one, the proportion of adults (15+) registered is modest (<40%). These proportions can be even lower when only affirmative decisions are considered. One nation provides priority status on the transplant waiting list as an incentive to affirmative registration, while another nation makes registering a donation decision mandatory to obtain a driver's license. Registered objections in non-donor registries are rare (<0.5%). The variation in organ donor registries worldwide necessitates public discourse and quality improvement initiatives, to identify and support leading practices in registry use.     

Matrix metalloproteinase protein expression profiles cannot distinguish between normal and early osteoarthritic synovial fluid

ABSTRACT: BACKGROUND: Osteoarthritis (OA) and Rheumatoid arthritis (RA) are diseases which result in the degeneration of the joint surface articular cartilage. Matrix Metalloproteinases (MMPs) are enzymes that aid in the natural remodelling of tissues throughout the body including cartilage. However, some MMPs have been implicated in the progression of OA and RA as their expression levels and activation states can change dramatically with the onset of disease. Yet, it remains unknown if normal and arthritic joints demonstrate unique MMPs expression profiles, and if so, can the MMP expression profile be used to identify patients with early OA. In this study, the synovial fluid protein expression levels for MMPs 1, 2, 3, 7, 8, 9, 12 & 13, as well as those for the Tissue Inhibitors of MMPs (TIMPs) 1, 2, 3, & 4 were examined in highly characterized normal knee joints, and knee joints with clinically diagnosed OA (early and advanced) or RA. The purpose of this study was to determine if normal, OA, and RA patients exhibit unique expression profiles for a sub-set of MMPs, and if early OA patients have a unique MMP expression profile that could be used as an early diagnostic marker. METHODS: Synovial fluid was aspirated from stringently characterized normal knee joints, and in joints diagnosed with either OA (early and advanced) or RA. Multiplexing technology was employed to quantify protein expression levels for 8 MMPs and 4 TIMPs in the synovial fluid of 12 patients with early OA, 17 patients diagnosed with advanced OA, 15 with RA and 25 normal knee joints. Principle component analysis (PCA) was used to reveal which MMPs were most influential in the distinction between treatment groups. K - means clustering was used to verify the visual grouping of subjects via PCA. RESULTS: Significant differences in the expression levels of MMPs and TIMPs were observed between normal and arthritic synovial fluids (with the exception of MMP 12). PCA demonstrated that MMPs 2, 8 & 9 can be used to effectively separate individuals diagnosed with advanced arthritis from early osteoarthritic and normal individuals, however, these MMP profiles do not separate early OA from normal synovial fluid. An apparent separation between advanced OA and RA subjects was also revealed through PCA. K-means clustering verified the presence of 3 clusters: normal joints clustered with early OA, and separate clusters of advanced OA or RA. CONCLUSIONS: This study demonstrates that unique MMP and TIMP expression profiles are present within normal, advanced OA and RA synovial fluid. These MMP profiles can be used to distinguish advanced OA & RA synovial fluid from early OA & normal synovial fluid, and even between synovial fluid samples from OA and RA joints. Although this methodology cannot be used for the diagnosis of early OA, high throughput multiplex technology of MMPs and TIMPs in synovial fluid may prove useful in determining the severity of the disease state, and/or quantifying the response of individuals to disease interventions.     

Dimethylamino Parthenolide Enhances the Inhibitory Effects of Gemcitabine in Human Pancreatic Cancer Cells

Introduction

Gemcitabine is standard treatment for pancreatic cancer but has limited clinical benefit due to chemoresistance. Nuclear factor-kappaB (NF-??B) can promote chemoresistance and is therefore an attractive therapeutic target. We hypothesize that NF-??B suppression with the novel, orally bioavailable inhibitor dimethylamino parthenolide (DMAPT) will sensitize pancreatic cancer cells to gemcitabine.

Methods

BxPC-3, PANC-1, and MIA PaCa-2 human pancreatic cancer cell lines were treated with gemcitabine and/or DMAPT. Effects on the NF-??B pathway were determined by electrophoretic mobility shift assay, ELISA, or Western blot. Proliferation and apoptosis were measured by cell counts and ELISA, respectively. The effect of gemcitabine in vivo was determined using a MIA PaCa-2 heterotopic xenograft model.

Results

Gemcitabine induced NF-??B activity in BxPC-3, PANC-1, and MIA PaCa-2 cells and decreased the level of the NF-??B inhibitor I??B?? in BxPC-3 and PANC-1 cells. DMAPT prevented the gemcitabine-induced activation of NF-??B. The combination of DMAPT/gemcitabine inhibited pancreatic cancer cell growth more than either agent alone. Gemcitabine also induced intratumoral NF-??B activity in vivo.

Conclusions

DMAPT enhanced the anti-proliferative effects of gemcitabine in association with NF-??B suppression in pancreatic cancer cells in vitro. Furthermore, gemcitabine induced NF-??B activity in vivo, thus supporting the evaluation of NF-??B-targeted agents to complement gemcitabine-based therapies.