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The expression of the anti-apoptotic protein BAG3 is induced in several cell types by exposure to high temperature, oxidants, and other stressful agents. We investigated whether exposure to 50 Hz electromagnetic fields raised BAG3 levels in the human melanoma cell line M14, in vitro and in orthotopic xenografts. Exposure of cultured cells or xenografts for 6 h or 4 weeks, respectively, produced a significant (P < 0.01) increase in BAG3 protein amounts. Interestingly, at the same times, we could not detect any significant variation in the levels of HSP70/72 protein or cell apoptosis. These results confirm the stressful effect of exposure to ELF in human cells, by identifying BAG3 protein as a marker of ELF-induced stress. Furthermore, they suggest that BAG3 induction by ELF may contribute to melanoma cell survival and/or resistance to therapy., (Copyright © 2011 Wiley-Liss, Inc.)

Lung cancer is the most common cancer in the world. One third of patients with non-small cell lung cancer (NSCLC) are diagnosed with locally or regionally advanced unresectable disease at presentation. Currently, in this stage of disease, a combination of chemotherapy and radiotherapy is the standard treatment approach for patients with good performance status, and concomitant chemo-radiotherapy has demonstrated to be the best therapeutic approach. However, despite improvements in treatment, local tumor control remains suboptimal and distant metastases remain the major site of failure. The diversity of molecular abnormalities in NSCLC may partly contribute to its resistance to therapy. It is therefore widely accepted that one approach to improve the efficacy of cancer therapy is the development of rational combinations of anticancer agents that may exhibit synergistic interactions. The introduction of several biologic agents represents an important advance in the management of NSCLC and some of them have shown to have a synergistic effect when given in combination with radiotherapy and chemotherapy in preclinical and in clinical models. In the present review we discuss the rationale and the feasibility of these combinations and the first results available from clinical trials.

Human leukemia results from multiple mutations that lead to abnormalities in the expressions and functions of genes that maintain the delicate balance between proliferation, differentiation and apoptosis. Continued research on the molecular aspects of leukemia cells has resulted in the developments of several potentially useful therapeutic agents. Discovery of new cellular and/or molecular pathways enabling innate or acquired resistance of cancers to current chemotherapeutics to be overcome is therefore of crucial importance if one wants to efficiently combat those cancers associated with dismal prognoses. In this concern, natural compounds are regarded as new chemical entities for the development of drugs against various pharmacological targets, including cancer, and, above all, leukemia.

Lung cancer is the major cause of cancer death in the world. Non Small Cell Lung Cancer (NSCLC) accounts approximately 80-85% of all lung cancer diagnosis; the majority of patients will be diagnosed with non operable, advanced-stage disease. Palliative chemotherapy and/or radiotherapy represent the standard of care of this disease. Platinum based doublets with third generation agents are considered the standard of first line advanced NSCLC treatment. However, data arising from the availability of pemetrexed suggest that histology could play a key role in decision making. Advances in understanding of the molecular pathogenesis of lung cancer have led to the identification of several specific targets such as vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) for therapeutic agents. Bevacizumab is the first recombinant humanized monoclonal antibody (mAb) binding VEGF to demonstrate clinical benefit and a rather survival prolongation in combination with chemotherapy in the treatment of non squamous chemo-naive advanced NSCLC patients. Two types of anti-EGFR targeting agents have reached advanced clinical development: mAbs and small molecule inhibitors of the EGFR tyrosine kinase enzymatic activity (TKIs). Among TKIs gefitinib has been tested in several phase II-III studies showing an improvement in survival and responses in first, second and third line treatment in selected patients with specific clinical and molecular characteristics. Furthermore, erlotinib has showed to significantly improve survival in an unselected population of patients following the failure of one or two chemotherapy regimens. This review will discuss the different therapeutic options for first and second line treatment in the clinical practice.

Non-small-cell lung cancer (NSCLC) is not considered to be immunogenic, but it may provide an accessible target for the properly primed immune system. Identifying lung tumor antigens and presenting them in the optimal context may enable the immune system to generate anti-lung tumor effector cells, which are usually absent. Despite encouraging preclinical and Phase I-II data, no specific active cancer vaccine has been approved for NSCLC therapy to date. Patient selection and measurable immune response methodology assessment could explain these negative results. Vaccine therapy has recently been re-emerging as a potential approach. This article discusses the Phase I, II and III trials investigating the most promising vaccines in the treatment of patients affected by any stage of NSCLC, thus providing a perspective on the future of this approach in this setting.

To date, lung cancer is still the leading cause of cancer-related mortality worldwide, with the majority of lung cancers arising in the elderly. As a consequence, we can expect an increase in the number of older lung cancer patients considered suitable for chemotherapy in the near future. Elderly patients often have comorbid conditions and progressive physiologic reduction of organ function, which can make the selection of proper treatment daunting. Some patients will be able to tolerate chemotherapy as well as their younger counterparts, whereas others will experience severe toxicity and require treatment modifications. Thus, a major issue is effectively selecting patients suitable for standard or attenuated therapy. A comprehensive geriatric assessment performed at baseline is a useful tool that can help select the best treatment regimen to be administered to elderly patients. Until now, few trials have specifically focused on elderly patients affected by non-small cell lung cancer (NSCLC), particularly those with advanced disease; prospective elderly-specific studies in early stages are still lacking. High priority should be given to evaluating the role of new targeted therapies. Unfortunately, to date, clinical trials that include functional status and comorbidity as part of the geriatric assessment are rare. Future trials, specifically in the elderly population, should include these kinds of evaluations. The most recent therapies for the treatment of elderly patients with NSCLC will be discussed here.

Introduction: For patients with advanced NSCLC, treatment outcomes are still disappointing and the search for new active and safe drugs is warranted. The chemotherapeutic agent pemetrexed has produced, in the last years, an innovation of therapeutic algorithms of this disease, and this review is aimed at describing the role of pemetrexed in the treatment of NSCLC., Areas Covered: In the present review, we discuss the mechanism of action of pemetrexed, its safety profile and the main clinical data on pemetrexed in NSCLC treatment. The reader will gain information on pemetrexed efficacy in the first-line, second-line and maintenance treatment of advanced NSCLC. Moreover, the histotype-based approach to NSCLC treatment, which is important for the selection of patients to be treated with pemetrexed, is clarified., Expert Opinion: The recent introduction of pemetrexed in the first-line and maintenance treatment of advanced non-squamous NSCLC represents, in our opinion, a significant step forward in the treatment of this disease in the last 3 years. Furthermore, cisplatin plus pemetrexed has a more favorable safety profile as compared with those of pre-existing cisplatin-based regimens.

Extremity vascular trauma is common in most urban trauma centers and controversy remains about the optimal management of arterial injuries. We examined the records of 188 patients who had lower extremity arterial trauma from September 1987 to April 1992 to help clarify these issues. There were 142 (75.5%) gunshot wounds, 18 (9.6%) stab wounds, 5 (2.7%) shotgun wounds, and 23 (12.2%) patients with blunt trauma. There were 43 (22.9%) associated venous injuries. There were 10 repair failures in the acute postoperative period. There were no repair failures for the iliac artery. Three failures involved the superficial femoral artery (SFA), six were popliteal, and one tibial. Vein and polytetrafluoroethylene (PTFE) grafts were used to repair the SFA with equal success. Repair of the popliteal artery with PTFE failed in four of five cases, while vein grafts failed in only 2 of 19 cases (p < 0.01). Graft failure was associated with blunt trauma in 8 of 23 patients (35%), and always resulted in amputation. Penetrating injuries accounted for only 2 of 165 (1.2%) failures and were successfully redone with no amputations. Venous injury was present in all SFA failures. Popliteal vein injury was present in two PTFE and two vein grafts that failed. There were no infections of vein or PTFE grafts. In conclusion, PTFE and vein have equal graft patency for the repair of the iliac and femoral arteries. However, the patency of PTFE was significantly worse in the popliteal location. Vein grafts should be used for repair of this vessel. Graft failure and amputation were more common with popliteal and tibial injuries from blunt mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

A small number of trauma patients with penetrating thoracic trauma will require formal pulmonary resections to repair severe injuries or control massive haemorrhage. Although previous reports on this subject have addressed the management of these injuries in battle conditions, civilian experience with this type of chest injury is limited. In a 3-year period, 259 patients underwent urgent thoracotomies for penetrating thoracic trauma. We retrospectively reviewed 43 patients who underwent lobectomies or pneumonectomies to control bleeding (93%) or bronchial injuries (7%). Handguns were the aetiologic agent in 41 patients (95%). The most common complication, pneumonia, was seen in 21 patients (87%). Fifteen patients (62%) developed respiratory failure. The complications of wound infection, post-operative haemorrhage and empyema were seen in equal frequency in four patients (16%). Two patients (8%) developed bronchopleural fistulas. Nine pneumonectomies and 34 lobectomies were performed with mortality rates of 66% and 38%, respectively (overall mortality, 44%). Ten (53%) deaths occurred in the operating room, late deaths (2-15 days) were secondary to sepsis and multiple organ dysfunction syndrome (MODS). Currently, the management of patients with devastating thoracic injuries to the thoracic cavity is divided into two stages. First, initial resuscitation with rapid surgery to control major bleeding, cardiac tamponade, tracheal disruptions and potentially lethal air embolism is indicated. Once the life-threatening conditions have been resolved, definitive surgical procedures are performed to repair injuries to any of the thoracic structures.

We surveyed directors of trauma at 408 trauma centers (as indicated by the state chairmen of the American College of Surgeons' Committee on Trauma [ACSCOT]). Of the 408 trauma directors 290 (71%) responded with information relative to their hospitals and the 1537 general surgeons taking trauma call. Altogether, 75% of the surgeons worked on an identified trauma service, 80% belonged to a cadre of surgeons identified as expert, 52% were viewed as full time, 25% provided in-house staff coverage, and 76% had completed an ATLS course. Six percent of the entire group were 60 to 73 years old and demonstrated a commitment to trauma equal to that of their younger cohorts. As a group, the older surgeons took less call, but when community or the institutional call needs were identified, the older surgeons met the challenge.

The use of laparoscopy in abdominal trauma has been proposed for several decades; however, it has not been widely used. With the advent of laparoscopic cholecystectomy, general surgeons are realizing the potential of this technique. This should result in an expanded role for laparoscopy, including the evaluation of abdominal trauma. We present a series in which laparoscopy was used in the evaluation of tangential gunshot wounds to the abdomen. Laparoscopy enabled us to demonstrate whether the missile had violated the peritoneal cavity and to avoid laparotomy in cases without peritoneal penetration.

Melanosis Coli (MC) is a benign pigmentation disorder of the colon occasionally diagnosed at endoscopy. The authors report a case of M. coli in a patient with a gunshot to the abdomen, in whom the entity produced an interesting clinical picture, and a review of the literature on this condition.

The use of pancreatic duct ligation (DL) during a Whipple procedure for trauma has been reported but not analyzed. We reviewed 13 cases of DL and compared the results with that reported for the Whipple procedure for trauma with pancreaticojejunostomy (PJ). The mortality rate of DL was 53.8%. Pancreatitis occurred in three cases (23.1%) and caused one death. Pancreatic fistulae occurred in 50% of patients surviving two or more days after DL. No long-term survivor developed overt diabetes mellitus. Malabsorption occurred in 50% of the long-term survivors of DL. When the DL and PJ groups were compared no statistically significant difference could be found in either mortality or pancreatic morbidity. The 46.2% survival rate for DL warrants its consideration as a technique available to trauma surgeons when faced with an unstable patient unable to tolerate further operative therapy.

There is no universally accepted standard classification for liver injuries, and thus accurate comparison of reports on the subject is impossible. Most published reports on liver trauma suggest that both morbidity and mortality have a linear correlation with not only the amount of liver parenchyma injured but also with the magnitude of the surgical intervention. The exceptions are retrohepatic vein injuries, which have a mortality independent of associated parenchymal injury but should be integrated in any classification of liver injury. The classification proposed is based on the segmental anatomy of the liver (as defined by Couinaud): Grade I--Injuries requiring no operative intervention, or any injury that requires operative intervention limited to a segment or less. Grade II--Any injury that requires operative intervention involving two or more segments. Grade III--Any injury with an associated juxta- or retrohepatic vein injury. We reviewed all patients with isolated liver injuries during the past 5 years and prospectively reviewed all patients for the 6-month period from January to June 1988 and applied this classification. Sixty-nine patients had grade I injuries, with one death (1%); thirteen patients had grade II injuries, with six deaths (46%); and 13 patients had grade III injuries with nine deaths (69%). Postoperative morbidity was 7% for grade I, 57% for grade II, and 50% for grade III. This study supports the conclusion that morbidity and mortality from liver injury are directly related to the volume of parenchyma involved, and that segmental anatomy can be applied to define this volume. Mortality from retrohepatic vein injuries is independent of associated parenchymal injury. We believe that this proposed classification will provide a simple, reproducible, and accurate means for reporting and comparing liver injuries.

In order to determine the usefulness of serum amylase and lipase in the initial evaluation and subsequent management of blunt abdominal trauma (BAT) patients, we collected serum amylase and lipase on 85 consecutive BAT patients at admission, hospital day 1, hospital day 3, and hospital day 7. Only one patient had a pancreatic injury. A total of 45 patients (53%) had at least one enzyme abnormality during the study. There was no correlation between amylase or lipase values and age, sex, type of injury, diagnostic tests, operation, and outcome. In a control group of nonabdominal-trauma patients with admit studies only, all enzyme values were normal. We conclude that serum amylase and lipase are randomly elevated in patients with nonpancreatic-BAT both initially and during subsequent hospitalization and are not useful clinical tools in these patients.

Because of difficulties in rapid exposure and control, injuries of the retrohepatic veins and retrohepatic vena cava continue to have mortality rates approaching 100%. Current strategies include shunt and finger fracture techniques, with controversy continuing over the optimal approach. We describe a new technique which involves mobilization of the liver by transecting the superhepatic vena cava, and affords a posterior approach to these injuries. Cadaveric dissection and clinical experience are described.

Eight patients with fecal incontinence were seen. All eight patients had massive splenomegaly secondary to myelofibrosis and myeloid metaplasia. Six of the eight patients underwent splenectomy for hypersplenism. Five of the six had total improvement of the fecal incontinence. One died two weeks postoperatively and could not be evaluated. In our opinion, the fecal incontinence was related to the splenomegaly. The possible mechanism is discussed. If absolutely necessary for control of fecal incontinence in this situation, splenectomy should be considered.