Efstathios Papalambros

Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: A phase II study.

Study objectives: The present study was conducted to evaluate the efficacy and safety of the combination of Oxaliplatin, Leucovorin and 5-FU as second line therapy, following relapse to Gemcitabine, in patients with advanced adenocarcinoma of the pancreas. Patients and methods: Patients with advanced pancreatic cancer previously treated with Gemcitabine were included in the study. All patients had histologically or cytologically confirmed adenocarcinoma of the pancreas that was unresectable, locally advanced or metastatic. Treatment consisted of Oxaliplatin 50 mg/m2 (2-hour iv infusion), followed by Leucovorin 50 mg/m2 (i.v. bolus) and 500 mg/m2 5-FU (1-hour iv infusion), administered weekly, until unacceptable toxicity or disease progression. Objective tumour response and toxicity were evaluated according to World Health Organisation (WHO) criteria. Results: A total of 30 patients, 20 men and 10 women, median age 63 years (range 52–71 years) and Karnofsky Performance Status (PS) of ≥50 entered the study. The majority of patients (96%) had locally advanced disease. A total of 380 doses of chemotherapy were delivered, a median of 12 doses per patient. Partial responses were observed in 7 patients (PR 23.3%), stable disease in 9 (SD 30.0%), while 14 patients progressed (PD 46.7%). Improved PS was observed in 18 (42.8%) patients. Patients that had responded to first-line Gemcitabine treatment were found more likely to respond or stabilize their disease with second-line treatment. The median duration of response was 22 weeks, and median overall survival was 25 weeks, Grade 3/4 toxicity expressed per chemotherapy dose included leukopenia 16%, anemia 3.2%, thrombocytopenia 3.2%, diarrhea 14.2%, fatigue 16.1% and neurotoxicity 4.2%. Eight patients (27%) suffered a febrile neutropenic event managed successfully with oral antibiotic home therapy, while 17 patients required G-CSF support. There were no treatment related deaths. Conclusions: The combination of Oxaliplatin, Leucovorin and 5-FU was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced or metastatic pancreatic adenocarcinoma, previously treated with Gemcitabine. Additional studies are warranted with this regimen in Gemcitabine relapsed pancreatic cancer patients.

Weekly Gemcitabine for the Treatment of Biliary Tract and Gallbladder Cancer

Objectives: To evaluate the efficacy and safety of weekly administration of gemcitabine treatment in chemotherapy-naïve patients with advanced biliary tract and gallbladder cancer. Patients and methods: Gemcitabine at a dose of 800 mg/m2 was administered weekly as a 30-min infusion to patients with previously operated, histologically confirmed, metastatic, or unresectable locally advanced cholangiocarcinoma. Treatment was continued until unacceptable toxicity or disease progression. Results: A total of 30 patients (median age 66 years; range 54–72 years) were included in the study. A median of 14 (range, 4–33) weekly doses was administered. Out of 30 patients evaluable for response, nine partial responses were observed (30.0%), while a further 11 patients demonstrated stable disease (36.7%). The median time to disease progression was 7 months (range, 5–34). Overall response rate was superior in patients with cancer of the gallbladder (ORR=35.7%) compared with those patients with biliary duct cancer (ORR=27.3%). This correlated to a significantly longer time to progression of 6.4 months (95% confidence interval (CI), 5.6–7.1 months) versus 3.6 months (95% CI, 2.9–4.3 months; p=0.03) and a significantly better overall survival of 17.1 months (95% CI, 15.8–18.5 months) versus 11.4 months (95% CI, 10.2–12.6 months, p=0.021). Toxicities were generally mild with only one case of grade 3 neutropenia. There were no cases of febrile neutropenia and no treatment-related deaths. Conclusions: Weekly administration of gemcitabine provides a safe, well-tolerated, and effective treatment for chemotherapy naïve patients with advanced cholangiocarcinoma, particularly with a gallbladder origin.

Fenestrated and Branched Endografts for the Treatment of Thoracoabdominal Aortic Aneurysms: A Systematic Review

Purpose: To offer a critical review of the current literature on the use of fenestrated and branched stent-grafts in patients with thoracoabdominal aortic aneurysms (TAAA). Methods: A thorough search of the English-language literature published between January 2000 and September 2009 identified reports of endovascular procedures using fenestrated and/or branched endografts as the intended repair strategy in patients with TAAA. Studies were selected based on specific inclusion criteria: (1) >3 high-risk patients with preoperative diagnosis of TAAA, (2) the intended treatment strategy was an endovascular repair using a fenestrated or branched endograft or both, and (3) patient demographics and outcome data (technical success rate, 30-day mortality, and follow-up length) were clearly stated. From 47 articles initially identified, 7 studies were included in the statistical analysis encompassing 155 patients (mean age 74.4 years, range 41–86) with TAAA averaging 69.2 mm in diameter. The mean follow-up was 11.8 months, and the majority of patients had Crawford type IV aneurysms. Outcome measures of eligible studies were tabulated and then analyzed cumulatively. Results: Technical success was achieved in 94.2% (n = 146) of the 155 patients. Twenty-three (18.4%) primary endoleaks were reported. The 30-day mortality was 7.1% (n = 11), while the 1-year survival rate was 82.6% (n = 128). Three (1.9%) patients developed permanent paraplegia and 2 (1.3%) developed permanent paraparesis; renal failure was reported in 9 (5.8%). Overall follow-up mortality was 16.1% (n=25). Conclusion: Endovascular treatment with fenestrated or/and branched stent-grafts is a new therapeutic option with encouraging results for patients considered unfit for conventional open repair. However, prolonged follow-up studies are needed in order to draw robust conclusions.

Cell-Assisted Lipotransfer

Adipose tissue is believed to constitute an ideal source of uncultured stromal stem cells. By optimizing the harvesting, storage, and transplantation of adipose tissue, long-lasting results can be obtained. Cell-assisted lipotransfer (CAL) is a novel approach to autologous fat transplantation in which adipose-derived stem cells are attached to the aspirated fat. The authors describe the cell processing methods, delivery systems, and clinical applications of CAL.

Bile Duct Injuries Associated with Laparoscopic and Open Cholecystectomy: An 11-Year Experience in One Institute

PurposeBile duct injury (BDI) represents the most serious complication of laparoscopic cholecystectomy (LC). The aim of this retrospective single-institution study was to evaluate the real incidence of BDI during laparoscopic and open cholecystectomy (OC) in a tertiary academic center in Athens, Greece.MethodsBetween January 1991 and December 2001, 3 637 patients underwent cholecystectomy in our department; as LC in 2 079 patients (LC group) and as OC in 1 558 patients (OC group). All the LCs were performed or supervised by five staff surgeons and all the OCs were performed or supervised by another five staff surgeons.ResultsThere were 13 BDIs associated with LC (0.62%) and 6 associated with OC (0.38%) (P = 0.317). There was one death associated with BDI after LC. Only two (15.4%) of the BDIs associated with LC occurred within the proposed learning curve limit of 50 LCs per individual surgeon.ConclusionLaparoscopic cholecystectomy is safe and is not associated with a higher incidence of BDI than OC. Moreover, we did not find that the learning curve for LC affected BDI occurrence.

Expression of Heregulin in Human Coronary Atherosclerotic Lesions

Background: Endothelial cells, monocytes/macrophages, and vascular smooth muscle cells contribute to the establishment and progression of atherosclerotic lesions by expressing growth and inflammatory factors. The aim of the present study was to determine whether heregulin (HRG) is associated with human coronary artery disease. Methods: Twenty-six fresh human coronary artery segments were collected at autopsy. Expression of cysteine-rich 61 (CYR61) and VEGF in response to HRG was studied in the human endothelial cell line EA.hy926, and expression of CYR61 and HRG was evaluated in activated macrophages isolated from peripheral blood of healthy donors. Results: We found that HRG was overexpressed at the protein and mRNA level in all lesions analyzed and gradually increased as the stages of the lesions progressed. Expression of HRG was observed in the intima primarily in macrophages. The same specimens were analyzed for the expression of CYR61, an angiogenetic factor regulated by HRG in breast cancer epithelial cells. CYR61 was expressed in both normal and atheromatic specimens, but its expression was significantly enhanced in macrophages of the intima. Activation of primary human macrophages results in increased expression of both HRG and CYR61. In addition, studies in endothelial cells where no endogenous HRG is present showed that HRG induces expression of CYR61 and secretion of VEGF. Conclusions: HRG may, therefore, play an important role in the development of coronary artery disease and the expansion of the atherosclerotic plaque and may locally regulate the expression of the angiogenetic factor CYR61.

Vascular Endothelial Growth Factor and Matrix Metalloproteinase 9 Expression in Human Carotid Atherosclerotic Plaques: Relationship with Plaque Destabilization via Neovascularization

Background: The aim of this study was to evaluate the potential impact of vascular endothelial growth factor (VEGF) on carotid plaque destabilization in association with matrix metalloproteinase 9 (MMP-9) production. Methods: Expression of VEGF and MMP-9 were determined immunohistochemically in 53 human endarterectomized atherosclerotic carotid plaques. The relationship to carotid plaque characteristics, clinical data and histological morphology was investigated. Results: VEGF and MMP-9 had parallel overexpression in the inflammatory cells, especially in the neovascularized plaque lesions and around the cholesterol crystals. Strong expression of VEGF was evident in symptomatic patients (p < 0.057), in high-degree stenosis (p = 0.005), and in patients with ischemic infarct in brain scan (p = 0.021). No relation was proved between molecule expression and plaque ultrasonic characteristics. Conclusions: An intense expression of VEGF and MMP-9 in carotid plaques is related to plaque instability, high degree of stenosis and presence of symptomatic carotid occlusive disease.

Surgical Treatment of Carotid Body Tumours

OBJECTIVE To evaluate our results of the treatment of patients with carotid body tumours. DESIGN Retrospective study. SETTING University hospital, Greece. SUBJECTS 17 patients operated on for a carotid body tumour during the past 20 years. MAIN OUTCOME MEASURES Hospital mortality and morbidity, long-term outcome. RESULTS 3 patients had temporary cranial nerve lesions postoperatively, all of which resolved within three months. One patient developed a severe stroke and died seven days postoperatively. During follow-up that ranged from 7 months to 20 years, two patients died of unrelated causes. 5 patients were lost to follow up, and the remaining 10 were doing well with no signs of recurrence at the time of writing. CONCLUSION Excision of a carotid body tumour is recommended at the time of initial diagnosis in good-risk patients to avoid the difficulty of subsequent excision of an enlarging and highly vascular tumour with possible encasement of the carotid artery.

Malondialdehyde as an indicator of oxidative stress during abdominal aortic aneurysm repair.

Ischemia-reperfusion injury significantly contributes to abdominal aortic aneurysm (AAA)— related mortality and morbidity; therefore, we measured oxidative stress during open AAA repair and investigated any potential associations with intraoperative or perioperative events (aortic clamping time, blood loss, and the need to transfer to the intensive care unit). Blood samples were collected at specific time points from 53 patients undergoing open AAA repair: (1) before induction of anesthesia; (2) 15, 30, 60, and 120 minutes after aortic clamping; (3) 15 and 60 minutes after clamp removal; and (4) 24 hours postoperatively. Malondialdehyde (MDA) levels were measured by a spectrophotometric method. Baseline MDA values in patients with AAA were significantly higher than in controls (P < .0001). A positive correlation was found between preoperative MDA levels and the size of AAAs (Pearson correlation = 0.578, P < .001). No difference was observed in MDA levels between ruptured and nonruptured AAAs; however, when all symptomatic patients (ruptured and elective symptomatic AAAs, n = 18) were considered, there was a significant elevation in MDA levels (P < .001). There was also a significant increase in MDA values in patients transferred postoperatively to the intensive care unit (P < .001). Finally, a positive association was found between the duration of aortic clamping with MDA values at 15 and 60 minutes after declamping, but not after 24 hours (Pearson correlation = 0.467, P < .001). MDA levels may predict the postoperative course of elective and ruptured AAAs.

Inflammatory pseudotumor associated with Mycobacterium tuberculosis infection

BACKGROUND Inflammatory pseudotumor is a relatively rare entity; originally identified in the lung, it has been described in multiple extrapulmonary anatomic locations. CASE REPORT We report on the unusual case of an inflammatory pseudotumor associated with Mycobacterium tuberculosis infection, which was initially mistaken for a renal malignancy both in clinical and radiological settings. We additionally present three brief reviews concerning: (1) infectious agents postulated to induce morphological changes of an inflammatory pseudotumor; (2) mycobacterial pseudotumors; and (3) distinction from inflammatory myofibroblastic tumors of the renal pelvis. CONCLUSIONS The present case highlights the diagnostic importance of PCR-based detection of mycobacterial DNA in granulomatous tissue responses. It is of crucial importance that clinicians are aware of this unusual manifestation of mycobacterial infection to ensure that pertinent laboratory evaluation is employed and appropriate treatment is administered in order to avoid potential clinical implications.