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Find video protocols related to scientific articles indexed in Pubmed.
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Combination of antiangiogenic therapy using the mTOR-inhibitor everolimus and low-dose chemotherapy for locally advanced and/or metastatic pancreatic cancer: a dose-finding study.
Anticancer Drugs
PUBLISHED: 07-17-2014
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Pancreatic adenocarcinomas are associated with a poor survival prognosis. Besides curative surgical resection, only limited therapies with modest impact are available. New evidence suggests that the mammalian target of rapamycin pathway may be involved in the pathogenesis of neuroendocrine tumors, and breast and renal cell cancer. The phase I study described here was therefore designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of escalating doses of the mammalian target of rapamycin inhibitor everolimus in combination with gemcitabine in patients with advanced pancreatic cancer. Eligible patients had histologically confirmed locally advanced and/or metastatic pancreatic carcinoma and were administered 5?mg everolimus every second day (cohort 1, 2, 3) or 5?mg daily (cohort 4, 5) in combination with escalating low-dose gemcitabine. It was found that if two patients showed DLTs, MTD was reached and gemcitabine dose escalation was stopped at this level. Twenty-seven patients were enrolled in the study (cohort 1: n=3; cohort 2: n=4; cohort 3: n=6; cohort 4: n=7; cohort 5: n=7) and received a maximum 600?mg gemcitabine/week. In cohort 5, two of the six patients experienced DLTs (grade 3 liver toxicity lasting for>7 days). MTD was measured as 400?mg/m/week gemcitabine plus 5?mg/day everolimus. The MTD of a low-dose gemcitabine treatment in combination with everolimus was determined and no new safety concerns were identified in patients with advanced pancreatic cancer.
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Side population cells of pancreatic cancer show characteristics of cancer stem cells responsible for resistance and metastasis.
Target Oncol
PUBLISHED: 05-09-2014
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Cancer stem cells (CSCs) have been proposed to underlie the initiation and maintenance of tumor growth and the development of chemoresistance in solid tumors. The identification and role of these important cells in pancreatic cancer remains controversial. Here, we isolate side population (SP) cells from the highly aggressive and metastatic human pancreatic cancer cell line L3.6pl and evaluate their potential role as models for CSCs. SP cells were isolated following Hoechst 33342 staining of L3.6pl cells. SP, non-SP, and unsorted L3.6pl cells were orthotopically xenografted into the pancreas of nude mice and tumor growth observed. RNA was analyzed by whole genome array and pathway mapping was performed. Drug resistant variants of L3.6pl were developed and examined for SP proportions and evaluated for surface expression of known CSC markers. A distinct SP with the ability to self-renew and differentiate into non-SP cells was isolated from L3.6pl (0.9 %?±?0.22). SP cells showed highly tumorigenic and metastatic characteristics after orthotopic injection. Transcriptomic analysis identified modulation of gene networks linked to tumorigenesis, differentiation, and metastasization in SP cells relative to non-SP cells. Wnt, NOTCH, and EGFR signaling pathways associated with tumor stem cells were altered in SP cells. When cultured with increasing concentrations of gemcitabine, the proportion of SP cells, ABCG2(+), and CD24(+) cells were significantly enriched, whereas 5-fluorouracil (5-FU) treatment lowered the percentage of SP cells. SP cells were distinct from cells positive for previously postulated pancreatic CSC markers. The Hoechst-induced side population in L3.6pl cells comprises a subset of tumor cells displaying aggressive growth and metastasization, increased gemcitabine-, but not 5-FU resistance. The cells may act as a partial model for CSC biology.
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PVA gel as a potential adhesion barrier: a safety study in a large animal model of intestinal surgery.
Langenbecks Arch Surg
PUBLISHED: 03-04-2014
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Intra-abdominal adhesions following surgery are a major source of morbidity and mortality including abdominal pain and small bowel obstruction. This study evaluated the safety of PVA gel (polyvinyl alcohol and carboxymethylated cellulose gel) on intestinal anastomoses and its potential effectiveness in preventing adhesions in a clinically relevant large animal model.
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Level of hospital care and outcome of gastric cancer: a population-based evaluation of the Munich Cancer Registry.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 02-26-2014
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Gastric cancer accounts for 5 % of cancer deaths. Successful implementation of guideline-recommended treatment procedures should result in population-based outcome improvements despite the still poor prognosis. In this context, the objective of this study was to compare the outcome of gastric cancer by different levels of hospital care.
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Loss of liver transplant surgeons into alternate career paths.
Transpl. Int.
PUBLISHED: 02-06-2014
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In Germany, long-term commitment of surgeons to transplantation is rare. Most surgeons leave transplant surgery after a short stint and follow careers in other surgical fields. This rapid turnover of liver transplant surgeons may result in poor resource utilization and potentially compromise patient safety. In this report, we have analyzed the caseload and the careers of 25 surgeons in liver transplantation over a period of 22 years. The median time in liver transplantation was short. Of all surgeons who engaged in liver transplantation, the median time was 3.5 years. Surgeons who completed their training remained in the field for 7 years. Surgeons who prematurely stopped their training remained for 2 years. Individual total caseloads of transplant surgeons were relatively low. The median number of procedures was 40 for all surgeons, 153 for currently active surgeons, 51 for surgeons who completed training, 27 for surgeons currently in training, and a median of four liver transplantations for surgeons who prematurely stopped liver transplantation. The vast majority (75%) of surgeons prematurely quit liver transplantation to follow alternate surgical careers. Structural changes in academic transplant surgery have to be made to facilitate long-term commitments of interested surgeons and to avoid "futile" transplant careers.
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Augmenter of liver regeneration attenuates inflammatory response in the postischemic mouse liver in vivo.
J. Surg. Res.
PUBLISHED: 01-11-2014
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Augmenter of Liver Regeneration (ALR), a protein synthesized in the liver is suggested to be protective against oxidative stress-induced cell death. Hepatic ischemia-reperfusion (I/R) injury is triggered by reactive oxygen species. Here, we tested the hypothesis that ALR attenuates hepatic I/R injury in vivo.
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Liver resection in the elderly: significance of comorbidities and blood loss.
J. Gastrointest. Surg.
PUBLISHED: 01-09-2014
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Liver resection is increasingly performed in elderly patients who are suspected of increased postoperative morbidity (PM) and reduced overall survival (OS). Patient selection based on the identification of age-adjusted risk factors may help to decrease PM and OS.
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Hypoxia-independent Gene Expression Mediated by Sox9 Promotes Aggressive Pancreatic Tumor Biology.
Mol. Cancer Res.
PUBLISHED: 12-03-2013
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Pancreatic cancer aggressiveness is characterized by its high capacity for local invasion, ability to promote angiogenesis, and potential to metastasize. Hypoxia is known to represent a crucial step in the development of aggressive malignant features of many human cancers. However, micrometastatic tumors are not typically subjected to hypoxic events during early stages of dissemination; therefore, it is unclear how these tumors are able to maintain their aggressive phenotype. Thus, the identification of regulators of hypoxia-related genes in aggressive/metastatic tumors represents a fundamental step for the design of future therapies to treat pancreatic cancer. To this end, transcriptomic profiles were compared between the non-metastatic pancreatic cancer cell line FG (LMET) and its angiogenic/metastatic derivate L3.6pl (HMET) under normoxic or hypoxic conditions. Cluster analysis revealed a number of transcripts that were induced by hypoxia in non-metastatic cancer cells. Strikingly, this cluster was determined to be constitutively activated under normoxia in the metastatic cancer cells and could not be further induced by hypoxia. A subset of these transcripts were regulated by the transcription factor Sox9 in the aggressive-metastatic cells, but driven by HIF-1alpha; in the parental non-metastatic cell line. Moreover, these transcripts were enriched in cancer-related networks including: WNT, CXCR4, retinoic acid, and FAK signaling pathways. In functional assays, inhibition of Sox9 expression in HMET cells led to increased apoptosis and reduced migration in vitro and a significant reduction in primary tumor growth, angiogenesis, and metastasis following orthotopic tumor cell injection. At the molecular level, the control of Sox9 expression was associated with changes in the methylation status of the Sox9 promoter. Finally, Sox9 up-regulation was verified in a series of pancreatic carcinoma patient-tumor specimens. Implications: Sox9 represents a novel target for pancreatic cancer therapy.
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Stem Cell-Like Side Populations in Esophageal Cancer: A Source of Chemotherapy Resistance and Metastases.
Stem Cells Dev.
PUBLISHED: 11-13-2013
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Dye-effluxing side population (SP) cells can be resistant to chemotherapy and are thought to resemble cancer stem cells. We characterized the relevance of the SP subpopulation in esophageal cancer cell lines and their relation to chemotherapy resistance and metastasis. The SP subpopulation was detected using Hoechst 33342 staining in five esophageal cancer cell lines OE19, OE21, OE33, PT1590, and LN1590. CTx-resistant cell lines were developed after long-term exposure to 5-fluorouracil (5-FU) and cisplatin and validated by analysis of resistance markers, thymidylate synthase and ERCC1. While neither LN1590 nor PT1590 had detectable SP cells, OE19, OE21, and OE33?cells were found to contain varying levels of SP cells. With increasing duration of 5-FU or cisplatin therapy, the SP subpopulation substantially emerged in PT1590 and LN1590. OE19-SP cells displayed significant higher tumorigenicity than OE19- non-SP (NSP) cells after subcutaneous tumor cell injection in vivo. SP cells isolated from OE19 and OE19/5-FUres were subsequently analyzed by an epithelial-to-mesenchymal transition (EMT) polymerase chain reaction array. Interestingly, the SP fraction of OE19/5-FUres showed a dramatic upregulation of EMT-related genes compared to the SP fraction of OE19. Our results provide evidence that (1) the proportion of SP cells is different in esophageal cancer, (2) SP cells exhibit stem cell properties and are associated to chemotherapy resistance, and (3) long-term CTx selects for SP cells with an upregulated EMT gene profile, which might be the source of systemic disease relapse. Further investigations are necessary to ideally target these EMT-associated SP cells in esophageal cancer.
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Metabolic self-destruction in critically ill patients: Origins, mechanisms and therapeutic principles.
Nutrition
PUBLISHED: 06-03-2013
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The aim of this study was to describe the evolution and nature of self-destructive metabolic responses observed in critically ill patients, and to analyze therapeutic principles on how best to avoid or diminish these responses.
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Long-term oncologic outcome after laparoscopic surgery for rectal cancer.
Surg Endosc
PUBLISHED: 05-28-2013
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Recent studies demonstrated favorable short- and mid-term results after laparoscopic surgery for rectal cancer. However, long-term results from large series are lacking. The present study analyses long-term results of laparoscopic rectal cancer surgery from a large-volume center.
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RNA stability in human liver: comparison of different processing times, temperatures and methods.
Mol. Biotechnol.
PUBLISHED: 05-28-2013
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The accuracy of information garnered by real-time quantitative polymerase chain reaction (RT-qPCR), an important technology for elucidating molecular mechanisms of disease, is dependent on tissue quality. Thus, this study aimed to determine the effects of intra-operative manipulation, extended processing times, different temperatures or storage in RNAlater on RNA quality in liver samples for tissue banking. Liver samples, flash-frozen or in RNAlater, were collected over a time course (during surgery before blood arrest up to 1 day after surgery) with samples kept either at room temperature (RT) or on ice. This study showed that at the longest time-point at RT, the RNA quality decreased significantly by 20%. However, relative gene expressions of FOS, GUSB, MYC, HIF1? and GFER were in general not significantly different when the time-points were compared. In conclusion, samples should be kept on ice during processing, and either RNAlater or snap-freezing should be utilised for storage. Further, intra-operative manipulation and extended postoperative processing time generally does not change relative gene expression levels for the 5 genes studied, making such sampling suitable for RT-qPCR analysis. Thus, if relative gene expression of a gene of interest is stable, these guidelines will lead to increased accrual of samples to the tissue bank.
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Perfusion characteristics of parotid gland tumors evaluated by contrast-enhanced ultrasound.
Eur J Radiol
PUBLISHED: 04-22-2013
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Contrast enhanced ultrasound (CE-US) is a promising imaging modality for non-invasive analysis of parotid gland lesions because their vascularisation differs from normal gland tissue. This clinical study should further investigate CE-US as a diagnostic tool for parotid gland tumors.
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Impact of cyclosporine versus tacrolimus on the incidence of de novo malignancy following liver transplantation: a single center experience with 609 patients.
Transpl. Int.
PUBLISHED: 04-10-2013
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De novo malignancies are a major cause of late death after liver transplantation. Aim of the present study was to determine whether use of cyclosporine versus tacrolimus affects long-term tumor incidence considering potential confounders. De novo malignancies in 609 liver transplant recipients at Munich Transplant Centre between 1985 and 2007 were registered. In 1996, the standard immunosuppressive regimen was changed from cyclosporine to tacrolimus. Different effects of those drugs on long-term tumor incidence were analyzed in multivariate analysis. During 3765 patient years of follow-up (median 4.78 years), 87 de novo malignancies occurred in 71 patients (mean age 47.5 ± 13.3 years, mean time after liver transplantation 5.7 ± 3.7 years). The cumulative incidence of de novo malignancies was 34.7% for all tumor entities after 15 years as compared to 8.9% for a nontransplanted population. The most frequent tumors observed were nonmelanoma skin cancers (44.83%). Moreover, post-transplant lymphoid disease, oropharyngeal cancer (n = 6, 6.9%), upper gastrointestinal tract cancer (n = 4, 4.6%), lung cancer (n = 4, 4.6%), gynecological malignancies (n = 4, 4.6%), and kidney cancer (n = 3, 3.45%) were detected. Multivariate analysis revealed recipient age [hazards ratio (HR) 1.06], male gender (HR 1.73), and tacrolimus-based immunosuppression (HR 2.06) as significant risk factors. Based on those results, a tacrolimus-based immunosuppression should be discussed especially in older male patients. Whether reducing tacrolimus target levels may reduce the risk for de novo malignancies has yet to be determined in prospective trials.
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Resection of sarcoma involving the intrahepatic vena cava: report of 2 cases from a specialized center.
Ann Vasc Surg
PUBLISHED: 03-29-2013
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Primary leiomyosarcoma (LMS) of the hepatic vena cava is a rare malignancy that has only been published in case reports. Only a few cases with successful R0 resection have been reported in the literature.
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Surgery for metastasis to the pancreas: is it safe and effective?
J Surg Oncol
PUBLISHED: 02-14-2013
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Pancreatic metastases are rare and only sparse data exists on treatment options. After recent advances in pancreatic surgery, metastasectomies have become promising treatment alternatives.
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Protocol TOP-Study (tacrolimus organ perfusion): a prospective randomized multicenter trial to reduce ischemia reperfusion injury in transplantation of marginal liver grafts with an ex vivo tacrolimus perfusion.
Transplant Res
PUBLISHED: 02-13-2013
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Critical organ shortage results in the utilization of extended donor criteria (EDC) liver grafts. These marginal liver grafts are prone to increased ischemia reperfusion injury (IRI) which may contribute to deteriorated graft function and survival. Experimental data have shown that the calcineurin inhibitor tacrolimus exerts protective effects on hepatic IRI when applied intravenously or directly as a hepatic rinse. Therefore, the aim of the present study is to examine the effects of an ex vivo tacrolimus perfusion on IRI in transplantation of EDC liver grafts.
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Clinical outcome of IBD-associated versus sporadic colorectal cancer: a matched-pair analysis.
J. Gastrointest. Surg.
PUBLISHED: 02-08-2013
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This study assesses the perioperative course and long-term survival of inflammatory bowel disease (IBD)-associated vs. sporadic colorectal cancer (IBD-CRC vs. SCRC) after elimination of known confounders.
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Selective targeting of genetically engineered mesenchymal stem cells to tumor stroma microenvironments using tissue-specific suicide gene expression suppresses growth of hepatocellular carcinoma.
Ann. Surg.
PUBLISHED: 11-02-2011
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The use of engineered mesenchymal stem cells (MSCs) as therapeutic vehicles for the treatment of experimental pancreatic and breast cancer has been previously demonstrated. The potential application of MSCs for the treatment of hepatocellular carcinoma (HCC) has been controversial. The general approach uses engineered MSCs to target different aspects of tumor biology, including angiogenesis or the fibroblast-like stromal compartment, through the use of tissue-specific expression of therapeutic transgenes. The aim of the present study was (1) to evaluate the effect of exogenously added MSCs on the growth of HCC and (2) the establishment of an MSC-based suicide gene therapy for experimental HCC.
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Antithrombin therapy in pancreas retransplantation and pancreas-after-kidney/pancreas-transplantation-alone patients.
Clin Transplant
PUBLISHED: 10-18-2011
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Antithrombin (AT) is a coagulatory inhibitor with pleiotropic activities. AT reduces ischemia/reperfusion injury and has been successfully used in patients with simultaneous pancreas kidney transplantation. This study retrospectively analyzes prophylactic high-dose AT application in patients with solitary pancreas transplantation traditionally related to suboptimal results. In our center, 31 patients received solitary pancreas transplantation between 7/1994 and 7/2005 (pancreas retransplantation, PAK/PTA). The perioperative treatment protocol was modified in 5/2002 now including application of 3000?IU. AT was given intravenously before pancreatic reperfusion (AT, n?=?18). Patients receiving standard therapy served as controls (n?=?13). Daily blood sampling was performed during five postoperative days. Standard coagulatory parameters and number of transfused red blood cell units were not altered by AT. In AT patients serum amylase (p?
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Targeted endothelial delivery of nanosized catalase immunoconjugates protects lung grafts donated after cardiac death.
Transplantation
PUBLISHED: 07-23-2011
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Donor organ shortage represents a major problem in lung transplantation. Donation after cardiac death could help to expand the pool of organs, but the additional period of warm ischemia after cardiac arrest aggravates primary graft dysfunction. The pulmonary endothelium of the graft constitutes an important source and target of reactive oxygen species generated during ischemia and reperfusion. Targeted protection of graft pulmonary endothelial cells by the antioxidant enzyme catalase, conjugated with a platelet/endothelial cell adhesion molecule-1 (PECAM-1) antibody to nanosized particles (anti-PECAM/catalase conjugates), might improve outcome in lung transplantation using donors after cardiac death and prolonged hypothermic preservation.
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Cancer stem cells and angiogenesis.
Int. J. Dev. Biol.
PUBLISHED: 07-07-2011
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Cancer stem cells (CSCs) or tumor initiating cells were identified and characterized as a unique subpopulation with stem cell features in many types of cancer. Current CSC studies provide novel insights regarding tumor initiation, progression, angiogenesis, resistance to therapy and interplay with the tumor micro-environment. A cancer stem cell niche has been proposed based on these findings. The niche provides the soil for CSC self-renewal and maintenance, stimulating essential signaling pathways in CSCs and leading to secretion of factors that promote angiogenesis and long term growth of CSCs. We present evidence which has emerged over the past 5 years indicating interaction of CSCs with angiogenesis in the proposed "vascular niche". Based on these findings, targeting the "cancer stem cell niche" by combining an individualized anti-CSC approach with treatment of their microenvironment may represent a novel therapeutic strategy against solid tumor systems.
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Infliximab does not affect postoperative complication rates in Crohns patients undergoing abdominal surgery.
Inflamm. Bowel Dis.
PUBLISHED: 06-26-2011
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In patients with Crohns disease (CD), the effect of anti-tumor necrosis factor alpha (TNF-?) antibody therapy on postoperative complications remains unclear. We aimed to determine the effects of infliximab on postoperative complication rates in patients undergoing abdominal surgery for CD.
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Spindle Cell Metaplastic Breast Carcinoma with Leiomyoid Differentiation: A Case Report.
Breast Care (Basel)
PUBLISHED: 06-14-2011
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BACKGROUND: Metaplastic carcinoma of the breast is a rare but distinct entity within the group of undifferentiated invasive carcinomas. This entity accounts for less than 0.5% of all breast cancers and contains elements of epithelial (ductal), mesenchymal, and intermediate forms of differentiation. Of these metaplastic carcinomas, there have been reports of chondroid, squamous, osseous, and spindle differentiation. CASE REPORT: We describe the clinical course of a 52-year-old female patient with an unusual histopathology of a spindle cell carcinoma of the breast, discuss the literature, and recommend an approach to diagnosis and treatment. The patient initially presented to an outside hospital with a rapidly growing breast mass that was originally diagnosed as a malignant phylloides tumor. She presented 11 months after the primary treatment with a local subcutaneous relapse. She later developed a local relapse of her metaplastic carcinoma in the chest wall. Extensive histopathological analysis lead to the diagnosis of a spindle cell metaplastic breast carcinoma with leiomyoid differentiation, which has not been described previously. CONCLUSIONS: Overlap in morphology can lead to a misinterpretation or underdiagnosis of metaplastic carcinomas. However, the prognosis is similar to more common types of breast adenocarcinoma.
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Pulmonary sclerosing hemangioma in a 21-year-old male with metastatic hereditary non-polyposis colorectal cancer: report of a case.
World J Surg Oncol
PUBLISHED: 06-06-2011
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Pulmonary sclerosing hemangioma (SH) is a rare tumor of the lung predominantly affecting Asian women in their fifth decade of life. SH is thought to evolve from primitive respiratory epithelium and mostly shows benign biological behavior; however, cases of lymph node metastases, local recurrence and multiple lesions have been described.
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Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination.
PLoS Pathog.
PUBLISHED: 05-24-2011
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Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+) heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+) transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination.
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Albumin synthesis rates are not responsive to hyperglycemic hyperinsulinemia in postoperative patients.
JPEN J Parenter Enteral Nutr
PUBLISHED: 04-30-2011
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Insulin regulates albumin synthesis in vitro and in various experimental models. The current study was undertaken to determine the effects of a physiologic hyperinsulinemia on albumin synthesis in postoperative patients in whom plasma albumin concentrations are decreased.
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Novel surgical technique for complete traumatic rupture of the pancreas: A case report.
J Med Case Rep
PUBLISHED: 04-25-2011
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Complete pancreatic rupture is a rare injury. The typical mechanism by which this occurs is overstretching of the pancreas across the vertebral column during blunt abdominal trauma. The management of this injury depends on the location and extent of the injury.
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Dendritic cell-based vaccination of patients with advanced pancreatic carcinoma: results of a pilot study.
Cancer Immunol. Immunother.
PUBLISHED: 04-10-2011
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Dendritic cell (DC)-based vaccination can induce antitumor T cell responses in vivo. This clinical pilot study examined feasibility and outcome of DC-based tumor vaccination for patients with advanced pancreatic adenocarcinoma.
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Linking transgene expression of engineered mesenchymal stem cells and angiopoietin-1-induced differentiation to target cancer angiogenesis.
Ann. Surg.
PUBLISHED: 04-05-2011
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To specifically target tumor angiogenesis by linking transgene expression of engineered mesenchymal stem cells to angiopoietin-1-induced differentiation.
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Short-term prognosis of critically ill surgical patients: the impact of duration of invasive organ support therapies.
J Crit Care
PUBLISHED: 04-01-2011
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We wanted to identify the importance of the duration of invasive ventilation and of renal replacement therapy for short-term prognosis of surgical patients treated in an intensive care unit (ICU).
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Arterial blood flow predicts graft survival in liver transplant patients.
Liver Transpl.
PUBLISHED: 03-30-2011
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Proper liver perfusion is essential for sufficient organ function after liver transplantation. The aim of this study was to determine the effects of portal and arterial blood flow on liver function and organ survival after liver transplantation. The arterial and portal venous blood flow was measured intraoperatively by transit time flow measurement after reperfusion for 290 consecutive liver transplants. The graft survival, hepatic cell damage (alanine aminotransferase and aspartate aminotransferase), and liver function (prothrombin ratio and bilirubin) were determined. Grafts were stratified into groups according to arterial blood flow measurements [<100 mL/minute for arterial blood flow group I (ART I), 100-240 mL/minute for ART II, and ? 240 mL/minute for ART III] and portal venous blood flow measurements (<1300 mL/minute for portal venous blood flow group I and ? 1300 mL/minute for portal venous blood flow group II). With multivariate analysis, the impact of blood flow on graft survival was determined, and potential confounders were considered. Decreased portal venous blood flow was associated with significantly less organ survival in univariate analysis but not in multivariate analysis. In contrast, the arterial blood flow was significantly correlated with organ survival after liver transplantation in univariate and multivariate analyses [hazard rate ratio = 2.5, confidence interval = 1.6-4.1, P < 0.001, median survival = 56.6 (ART I), 82.7 (ART II), or 100.7 months (ART III)]. Moreover, low arterial blood flow resulted in impaired postoperative organ function and higher rates of primary nonfunction. Biliary complications were not affected by blood flow. Other risk factors for graft failure that were identified by multivariate analysis included retransplantation, histidine tryptophan ketoglutarate solution versus University of Wisconsin solution, and donor treatment with epinephrine. Impaired arterial blood flow after reperfusion represents a significant predictor of primary graft nonfunction and is associated with impaired graft survival. Whether the intraoperative measurement of hepatic arterial flow is predictive of graft survival should be evaluated in a prospective trial.
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Tacrolimus preconditioning of rat liver allografts impacts glutathione homeostasis and early reperfusion injury.
J. Surg. Res.
PUBLISHED: 03-22-2011
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To characterize the immunosuppressant tacrolimus as a protective antioxidant in rat liver transplantation.
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Laparoscopic anterior hemifundoplication and hiatoplasty for the treatment of upside-down stomach: mid- and long-term results after 40 patients.
Surg Endosc
PUBLISHED: 02-27-2011
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Treatment of type 4 hiatal hernia using a minimally invasive approach is challenging and requires good familiarity with this technique.
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Immunotherapy of peritoneal carcinomatosis with the antibody catumaxomab in colon, gastric, or pancreatic cancer: an open-label, multicenter, phase I/II trial.
Onkologie
PUBLISHED: 02-18-2011
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Peritoneal carcinomatosis (PC) is common in gastrointestinal (GI) cancer and there is no effective standard treatment. We investigated the tolerability and maximum tolerated dose (MTD) of the trifunctional antibody catumaxomab in patients with PC.
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Effects of pharmaceutical counselling on antimicrobial use in surgical wards: intervention study with historical control group.
Pharmacoepidemiol Drug Saf
PUBLISHED: 01-24-2011
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The objective of this study was to assess the impact of pharmaceutical consulting on the quality of antimicrobial use in a surgical hospital department in a prospective controlled intervention study.
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Active-specific immunotherapy for non-small cell lung cancer.
J Thorac Dis
PUBLISHED: 01-10-2011
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Non-small cell lung cancer constitutes about 85% of all newly diagnosed cases of lung cancer and continues to be the leading cause of cancer-related deaths worldwide. Standard treatment for this devastating disease, such as systemic chemotherapy, has reached a plateau in effectiveness and comes with considerable toxicities. For all stages of disease fewer than 20% of patients are alive 5 years after diagnosis; for metastatic disease the median survival is less than one year. Until now, the success of active-specific immunotherapy for all tumor types has been sporadic and unpredictable. However, the active-specific stimulation of the hosts own immune system still holds great promise for achieving non-toxic and durable antitumor responses. Recently, sipuleucel-T (Provenge(®); Dendreon Corp., Seattle, WA) was the first therapeutic cancer vaccine to receive market approval, in this case for advanced prostate cancer. Other phase III clinical trials using time-dependent endpoints, e.g. in melanoma and follicular lymphoma, have recently turned out positive. More sophisticated specific vaccines have now also been developed for lung cancer, which, for long, was not considered an immune-sensitive malignancy. This may explain why advances in active-specific immunotherapy for lung cancer lag behind similar efforts in renal cell cancer, melanoma or prostate cancer. However, various vaccines are now being evaluated in controlled phase III clinical trials, raising hopes that active-specific immunotherapy may become an additional effective therapy for patients with lung cancer. This article reviews the most prominent active-specific immunotherapeutic approaches using protein/peptide, whole tumor cells, and dendritic cells as vaccines for lung cancer.
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Enteric conversion after pancreatic transplantation: resolution of symptoms and long-term results.
Clin Transplant
PUBLISHED: 11-28-2010
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Bladder drainage (BD) of pancreatic transplants is associated with a unique set of complications. We intended to analyze the incidence, indications, complications and long-term results of enteric conversion procedures (EC).
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Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis.
Biochem. Biophys. Res. Commun.
PUBLISHED: 11-10-2010
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Augmenter of liver regeneration (ALR) is known to support liver regeneration and to stimulate proliferation of hepatocytes. However, it is not known if ALR exerts anti-apoptotic effects in human hepatocytes and whether this protective effect is cell type specific. This is relevant, because compounds that protect the liver against apoptosis without undesired effects, such as protection of metastatic tumour cells, would be appreciated in several clinical settings. Primary human hepatocytes (phH) and organotypic cancer cell lines were exposed to different concentrations of apoptosis inducers (ethanol, TRAIL, anti-Apo, TGF-?, actinomycin D) and cultured with or without recombinant human ALR (rhALR). Apoptosis was evaluated by the release of cytochrome c from mitochondria and by FACS with propidium iodide (PI) staining. ALR significantly decreased apoptosis induced by ethanol, TRAIL, anti-Apo, TGF-? and actinomycin D. Further, the anti-apoptotic effect of ALR was observed in primary human hepatocytes and in HepG2 cells but not in bronchial (BC1), colonic (SW480), gastric (GC1) and pancreatic (L3.6PL) cell lines. Therefore, the hepatotrophic growth factor ALR acts in a liver specific manner with regards to both its mitogenic and its anti-apoptotic effect. Unlike the growth factors HGF and EGF, rhALR acts in a liver specific manner. Therefore, ALR is a promising candidate for further evaluation as a possible hepatoprotective factor in clinical settings.
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Co-morbidity and postsurgical outcome in patients with perforated sigmoid diverticulitis.
Int J Colorectal Dis
PUBLISHED: 07-14-2010
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It was previously reported that in patients with acute perforated diverticulitis with Hinchey categories I to III sigmoidectomy with primary anastomosis (PA) is superior to Hartmanns procedure (HP) as later closure of colostomy involves substantial morbidity. We evaluated our experience with PA for patients with perforated diverticulitis over a 10-year period and aimed to investigate whether Hinchey category or co-morbidity are more relevant for postoperative outcome.
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Late reuse of liver allografts from brain-dead graft recipients: the Munich experience and a review of the literature.
Liver Transpl.
PUBLISHED: 06-03-2010
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The increasing donor organ shortage requires the consideration of any possible organ donor in order to meet the current demand. However, the growing number of long-term survivors of liver transplantation may create a situation in which former organ recipients may experience brain death with a functioning graft and therefore become organ donors themselves. Previous reports concerning this rare situation predominantly refer to the reuse of donor organs within the first 8 days after primary liver transplantation. So far, only a single case of late reuse of a donor liver has been published, with 2 additional cases mentioned in a summary of the United Network for Organ Sharing database. Here we report the case of a 43-year-old female donor who had received a liver graft for complications of Budd-Chiari syndrome 5 years before becoming an organ donor herself after cerebral infarction with consecutive brain death.
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The prognostic value of lymph node ratio in a population-based collective of colorectal cancer patients.
Ann. Surg.
PUBLISHED: 05-21-2010
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We analyzed 3 previously identified cut-off values of lymph node ratios (0.17, 0.41, and 0.69) in a large population-based collective of patients with colorectal cancer for their prognostic value.
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Long-term survival after surgical critical illness: the impact of prolonged preceding organ support therapy.
Ann. Surg.
PUBLISHED: 05-21-2010
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To identify the prognostic importance of preceding invasive ventilation, renal replacement therapy, and catecholamine therapy for long-term survivors after surgical critical illness.
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A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma.
BMC Cancer
PUBLISHED: 05-11-2010
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The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.
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A prospective, randomised, controlled, double-blind phase I-II clinical trial on the safety of A-Part Gel as adhesion prophylaxis after major abdominal surgery versus non-treated group.
BMC Surg
PUBLISHED: 05-10-2010
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Postoperative adhesions occur when fibrous strands of internal scar tissue bind anatomical structures to one another. The most common cause of intra-abdominal adhesions is previous intra-abdominal surgical intervention. Up to 74% of intestinal obstructions are caused by post surgical adhesions. Although a variety of methods and agents have been investigated to prevent post surgical adhesions, the problem of peritoneal adhesions remains largely unsolved. Materials serving as an adhesion barrier are much needed.
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Atrial resection for lung cancer: morbidity, mortality, and long-term follow-up.
World J Surg
PUBLISHED: 05-04-2010
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The purpose of this study was to examine our results of combined resection of the atrium and non-small-cell lung cancer using a concurrent and continuously updated database.
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Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study.
Lancet Oncol.
PUBLISHED: 04-29-2010
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The optimum treatment for high-risk soft-tissue sarcoma (STS) in adults is unclear. Regional hyperthermia concentrates the action of chemotherapy within the heated tumour region. Phase 2 studies have shown that chemotherapy with regional hyperthermia improves local control compared with chemotherapy alone. We designed a parallel-group randomised controlled trial to assess the safety and efficacy of regional hyperthermia with chemotherapy.
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Anastomotic leakage after esophageal resection: new treatment options by endoluminal vacuum therapy.
Ann. Thorac. Surg.
PUBLISHED: 04-17-2010
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Anastomotic leakage after esophagectomy is an important determinant of early and late morbidity and mortality. Control of the septic focus is essential when treating patients with anastomotic leakages. Surgical and endoscopic treatment options are limited.
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Risk factors for surgical complications in distal pancreatectomy.
Am. J. Surg.
PUBLISHED: 04-09-2010
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Pancreatic fistula (PF) represents a major complication after distal pancreatectomy. In a consecutive series of 110 patients, risk factors for the incidence of PF and surgical morbidity were identified.
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Vascular targeting tumor therapy: non-invasive contrast enhanced ultrasound for quantitative assessment of tumor microcirculation.
Cancer Biol. Ther.
PUBLISHED: 03-18-2010
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The aim of the study was to quantitatively assess tumor microcirculation upon vascular targeting tumor therapy by non-destructive contrast enhanced ultrasonography (CEUS) and to validate this technology by correlation with high-resolution intravital fluorescence microscopy (IVM). Subcutaneous Lewis Lung carcinomas (LLC-1) carcinomas were established in mice. A-MEL-3 melanomas were grown in dorsal skinfold chambers of hamsters to permit bimodal imaging of tumor microcirculation by CEUS and IVM. Animals were treated by i.p. injection of ZD6126 and CEUS imaging after bolus injection of microbubbles was performed. Red blood cell velocity (VRBC), segmental blood flow (Q) and microcirculatory perfusion (PI) of tumors was quantified by IVM. Change in signal intensity (SI) from baseline (?SI), rate of SI increase (RSI) and area below intensity time curves (AUC) were calculated in tumors by analysis of CEUS data. Microvessel density was measured by quantitative analysis of CD31 immunohistochemistry. The Mann-Whitney test was used to evaluate differences between groups. Spearman correlation test was used to investigate the relation between CEUS and IVM parameters or histologic CD31 count. ?SI, RSI and AUC values in ZD6126 treated tumors were lower compared to untreated controls. Comparing central and peripheral tumor regions a vascularized viable rim in the tumor periphery could be detected by CEUS imaging. For the entire cohort ?SI, RSI and AUC values positively correlated with VRBC, Q and PI quantified by IVM. In LLC-1 carcinomas a positive correlation between ?SI, RSI and AUC and histological assessment of tumor vascularity was found. In conclusion tumor vascular response to vascular targeting therapy can be quantified non-invasively by CEUS. Bimodal tumor imaging by intravital microscopy and CEUS represents an experimental tool to further develop molecular imaging of tumor microcirculation by CEUS.
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Augmenter of liver regeneration causes different kinetics of ERK1/2 and Akt/PKB phosphorylation than EGF and induces hepatocyte proliferation in an EGF receptor independent and liver specific manner.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-09-2010
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Augmenter of liver regeneration (ALR) is a potent growth factor which supports liver regeneration in experimental animals. The aim of this study was to compare proliferation as well as the kinetics of ERK1/2 and Akt/PKB phosphorylation by recombinant human ALR (rhALR) and EGF in human hepatocytes and extrahepatic cells.
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Description and evaluation of a bench porcine model for teaching surgical residents vascular anastomosis skills.
BMC Res Notes
PUBLISHED: 02-16-2010
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Numerous models, of variable quality, exist to impart the complex skills required to perform vascular anastomosis. These models differ with regard to the kinds of materials used, as well as their sizes, the time needed for their preparation, their availability, and the associated costs. The present study describes a bench model that uses formalin-fixed porcine aorta, and its evaluation by young surgical residents during a recent skills course.
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Stapled transanal rectal resection for symptomatic intussusception: morphological and functional outcome.
Surg Endosc
PUBLISHED: 02-05-2010
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Stapled transanal rectal resection (STARR) was developed to correct intussusception causing obstructed defecation. Some patients, however, do not profit from this operation as anticipated. We aimed to study the relationship between functional outcome and rectal morphology after STARR.
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The intrinsic renal compartment syndrome: new perspectives in kidney transplantation.
Transplantation
PUBLISHED: 01-12-2010
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Inflammatory edema after ischemia-reperfusion may impair renal allograft function after kidney transplantation. This study examines the effect of edema-related pressure elevation on renal function and describes a simple method to relieve pressure within the renal compartment.
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Immunotherapy of cancer: key findings and commentary on the third Tegernsee conference.
Oncologist
PUBLISHED: 01-08-2010
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Cancer immunotherapy broadly includes active immunization, as in the use of cancer vaccines, passive immunization, such as the use of adoptive cell therapy and antibodies that modulate tumor function, and immunostimulation, using antibodies and small molecules to treat malignancy by activating or unleashing an endogenous immune response against tumor cells. Currently, >100 different monoclonal antibodies are in use or under evaluation for use as therapeutic agents in various malignancies. Active stimulation of the hosts immune system holds promise for achieving durable remission of malignant disease and represents a nontoxic method of therapy if tumor-specific effector cells can be selectively targeted. However, no active-specific treatment strategy (i.e., a therapeutic cancer vaccine) has yet found its way into the clinical armamentarium, although several promising recent reports suggest that, for follicular lymphoma, prostate cancer, and melanoma, clinical benefit was shown for the first time in randomized trials with a vaccine approach. Here, we report on the key findings of the Third Tegernsee Conference on Immunotherapy of Cancer (Feldafing, Germany, July 2-4, 2009) and provide short commentaries on data presented at this meeting regarding the future role of cancer vaccines, recent developments in adoptive cellular therapy, ways to improve immunotherapeutic treatment modalities (e.g., by manipulating the tumor microenvironment), and some novel targeted therapies that are well advanced in clinical testing, all of which have implications for future oncology practice.
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Lysis of cancer cells by autologous T cells in breast cancer pleural effusates treated with anti-EpCAM BiTE antibody MT110.
Breast Cancer Res. Treat.
PUBLISHED: 12-17-2009
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In the present study, the efficacy of a new drug, i.e. the bispecific single-chain antibody MT110 targeting the epithelial antigen EpCAM and the T-cell antigen CD3 was tested ex vivo in malignant pleural effusions (MPEs). EpCAM+ epithelial cells were found in 78% of the MPEs (n = 18). Ex vivo treatment of seven MPEs resulted in a dose-dependent specific lysis of 37 +/- 27% (+/- SD) EpCAM+ cells with 10 ng/ml (P = 0.03) and 57 +/- 29.5% EpCAM+ cells with 1,000 ng/ml MT110 (P = 0.016) after 72 h. As a prerequisite for redirected lysis, stimulation of the autologous CD4+ and CD8+ cells in MPE by 1,000 ng/ml MT110 resulted in 21 +/- 17% CD4+/CD25+ and 29.4 +/- 22% CD8+/CD25+ cells (P = 0.016, respectively) after 72 h. This was confirmed by a 22-fold release of TNF-alpha and 230-fold release of IFN-gamma (1,000 ng/ml, 48 h, P = 0.03, respectively). Thus, relapsed breast cancer patients resistant to standard treatment might benefit from targeted therapy using MT110.
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Targeting tumor stroma using engineered mesenchymal stem cells reduces the growth of pancreatic carcinoma.
Ann. Surg.
PUBLISHED: 10-15-2009
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To analyze the efficacy of engineered mesenchymal stem cell based therapy directed towards pancreatic tumor stroma.
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EFEMP1 binds the EGF receptor and activates MAPK and Akt pathways in pancreatic carcinoma cells.
Biol. Chem.
PUBLISHED: 10-07-2009
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The EGF-related protein EFEMP1 (EGF-containing fibulin-like extracellular matrix protein 1) has been shown to promote tumor growth in human adenocarcinoma. To understand the mechanism of this action, the signal transduction activated upon treatment with this protein has been investigated. We show that EFEMP1 binds EGF receptor (EGFR) in a competitive manner relative to epidermal growth factor (EGF), implicating that EFEMP1 and EGF share the same or adjacent binding sites on the EGFR. Treatment of pancreatic carcinoma cells with purified EFEMP1 activates autophosphorylation of EGFR at the positions Tyr-992 and Tyr-1068, but not at the position Tyr-1048. This signal is further transduced to phosphorylation of Akt at position Thr-308 and p44/p42 MAPK (mitogen-activated protein kinase) at positions Thr-202 and Tyr-204. These downstream phosphorylation events can be inhibited by treatment with the EGFR kinase inhibitor PD 153035. The observed signal transduction upon treatment with EFEMP1 can contribute to the enhancement of tumor growth shown in pancreatic carcinoma cells overexpressing EFEMP1.
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Esophageal leiomyomatosis combined with intrathoracic stomach and gastric volvulus.
JSLS
PUBLISHED: 10-02-2009
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A 42-year-old female presented with long-standing symptoms suggestive of gastroesophageal reflux disease improved after proton pump inhibitor treatment. An upper endoscopy revealed an intrathoracic position of the stomach (type 4 hiatal hernia) with no mucosal abnormality. Barium swallow demonstrated gastric herniation with gastric volvulus without stenosis. A computed tomographic scan confirmed the intrathoracic location of the stomach associated with thickening and edema of the gastric wall due to gastric volvulus, but no evidence of malignancy. The patient was scheduled for laparoscopic gastric repositioning with anterior hemifundoplication. Due to the incidental intraoperative finding of a large distal esophageal tumor (frozen section: esophageal leiomyomatosis), the operation was converted to conventional distal esophagectomy and proximal gastrectomy with reconstruction using a Merendino procedure. Final histology revealed extensive circumferential leiomyomatosis of the distal esophagus with a diameter of 10 cm. Esophageal leiomyomatosis is an extremely rare pathological finding with <100 cases reported in the literature.
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Accuracy of procalcitonin for outcome prediction in unselected postoperative critically ill patients.
Shock
PUBLISHED: 08-22-2009
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The importance of postoperative procalcitonin (PCT) measurements for outcome prediction is currently controversial. Conflicting results have been obtained for patients after polytrauma, sepsis, peritonitis, or cardiac surgery and may result from incomplete adjustment for important confounders or from nonlinear PCT effects. We retrospectively analyzed the association of PCT concentration with postoperative mortality, morbidity, and length of stay in an unselected series of 220 consecutive patients who required postoperative intensive care unit therapy or surveillance. Biochemical markers were measured on the first day after intensive care unit admission. Results were adjusted for various confounding variables (Acute Physiology and Chronic Health Evaluation II score, underlying disease), and test accuracy was evaluated by receiver operating characteristic statistics. We found a significant nonlinear, logarithmic association between PCT concentration and outcome. After adjustment for relevant covariates, PCT was an independent determinant of mortality, combined mortality/morbidity, and postoperative hospital length of stay in survivors. At mortality analysis, the predictive power of PCT was superior to that of Acute Physiology and Chronic Health Evaluation II score and of IL-6 (optimal cutoff point, 1.44 ng/mL; sensitivity, 80.8%; specificity, 80.4%). The use of PCT was comparable to that of other prognostic markers when combined mortality/morbidity were examined. Our results suggest that PCT may deserve further testing as a prognostic tool in unselected, critically ill, surgical patients.
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Prognostic factors in critically ill patients suffering from secondary peritonitis: a retrospective, observational, survival time analysis.
World J Surg
PUBLISHED: 08-06-2009
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Acute mortality of unselected critically ill patients has improved during the last 15 years. Whether these benefits also affect survival of critically ill patients with secondary peritonitis is unclear as is the relevance of specific prognostic factors, such as source control.
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Prothrombin complex concentrate in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding.
Crit Care
PUBLISHED: 07-08-2009
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Prothrombin complex concentrates are recommended for rapid reversal of vitamin K anticoagulants. As they normalize levels of vitamin K dependent clotting factors and re-establish hemostasis, they may also be used as adjunctive therapy in patients with major bleeding. The aim of this study was to retrospectively evaluate the efficacy of prothrombin complex concentrates in the surgical setting.
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Recipient treatment with L-arginine attenuates donor lung injury associated with hemorrhagic shock.
Transplantation
PUBLISHED: 06-09-2009
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Organ donors are frequently trauma victims, but the impact of donor hemorrhagic shock and resuscitation (HSR) on pulmonary graft function has not been assessed. L-arginine treatment during reperfusion increases the production of endothelial nitric oxide and thus ameliorates ischemia-reperfusion injury. Objective of the present porcine study was to investigate the effect of donor hemorrhage on pulmonary graft function and potential beneficial effects of L-arginine administration.
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Combined supra-aortic extra-anatomic revascularization and endovascular hybrid procedure for recurrent hemoptysis caused by a symptomatic aneurysm of the right subclavian artery.
Vascular
PUBLISHED: 05-30-2009
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Acute hemoptysis might be caused by aneurysms of the subclavian artery. We report a 75-year-old female patient presenting with recurrent hemoptysis, dyspnea, fever, and episodes of unclear pneumonia. Further examination revealed a large intrathoracic aneurysm of the right subclavian artery. After an initial transfemoral interventional attempt to occlude the entry of the aneurysm, the patient developed persistent thoracic pain. The patient was then treated by a combined extrathoracic hybrid procedure with a left to right carotid-carotid-axillary artery bypass and an endovascular aneurysm exclusion by insertion of two iliac artery occluder stent grafts in the proximal brachiocephalic trunk and the distal right subclavian artery. After this combined intervention, hemoptysis disappeared, and the patient recovered remarkably during a follow-up of 24 months.
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Determinants of morbidity and survival after elective non-curative resection of stage IV colon and rectal cancer.
Int J Colorectal Dis
PUBLISHED: 05-13-2009
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The benefit of elective primary tumor resection for non-curable stage IV colorectal cancer (CRC) remains largely undefined. We wanted to identify risk factors for postoperative complications and short survival.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.