Christos Tsigris

Serum levels of E-selectin, ICAM-1 and VCAM-1 in colorectal cancer patients: correlations with clinicopathological features, patient survival and tumour surgery

The serum concentrations of the cell adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 63 patients with colorectal cancer and in 51 controls by an enzyme-linked immunosorbent assay (ELISA). Their relationship to clinicopathological variables and patient survival and changes in their levels after surgery were examined. Colorectal cancer patients showed significantly higher serum levels of E-selectin, ICAM-1 and VCAM-1 compared with healthy controls. There was a significant association between the serum levels of these molecules, disease stage and the presence of both lymph node and distant metastases. Both ICAM-1 and VCAM-1 levels correlated with serum E-selectin and carcinoembryonic antigen (CEA) levels. Serum levels of all three molecules decreased significantly after radical resection of the tumour. Elevated pre-operative E-selectin, ICAM-1 and VCAM-1 levels were significant prognostic factors, although not independent of stage, for patient survival. These findings suggest that serum concentrations of E-selectin, ICAM-1 and VCAM-1 may reflect tumour progression and metastasis. Since these markers are linked to CEA levels, it is uncertain whether their measurement will prove cost-effective in colorectal cancer management.

Hypersensitivity Reactions to Carboplatin Administration Are Common but Not Always Severe: A 10-Year Experience

We have retrospectively evaluated and characterized the hypersensitivity reactions associated with carboplatin administration in ovarian cancer patients treated mainly on an outpatient basis at the Laikon Hospital from 1988 to 1998. A total of 240 patients, who had never been exposed to platinum compounds previously, received carboplatin plus cyclophosphamide (n = 58) or paclitaxel (n = 136) intravenously, and intraperitoneal carboplatin plus intravenous cyclophosphamide (n = 46). The median number of carboplatin courses was 6 (range 3–12) and 5 (range 4–6) for the intravenous and intraperitoneal treatment regimens, respectively. Thirty-two of 194 patients (16%) who were on intravenous carboplatin treatment developed symptoms compatible with a hypersensitivity reaction to carboplatin, that was always verified by manifestation of at least similar symptoms on rechallenging. In contrast, in the group of 46 patients on intraperitoneal carboplatin treatment, no hypersensitivity reaction was ever noticed. Hypersensitivity reactions always occurred after administration of the first 4 intravenous courses of carboplatin; 4, 19, 4, and 5 reactions occurred at the 5th, 6th, 7th, and 8th courses, respectively. These reactions could be distinguished in: (a) mild hypersensitivity reactions in 20 of 194 patients, which manifested as itching (20 patients) and small area erythema plus erythema of the palms and soles (12 patients), occurring either during intravenous injection when most of the drug scheduled had been administered, or within 3 days, and (b) in severe reactions in 12 of 194 patients, which manifested acutely as itching, diffuse erythroderma, rigor, facial swelling, throat and chest tightness, tachycardia (12 patients) and bronchospasm (2 patients), and hypertension or hypotension in 8 and 4 patients, respectively. With appropriate symptomatic management, discontinuation of carboplatin treatment was not required in patients with mild hypersensitivity reactions, but none of the 12 patients with severe reactions was able to receive a full subsequent dose of carboplatin on rechallenging. However, in 4 of these 12 patients carboplatin was replaced by cisplatin, which was given for 4–6 courses without side effects. These findings indicate that although hypersensitivity reactions are common in general, occurring in almost 1 of every 6 patients treated intravenously with carboplatin, their clinical picture is variable, leading to discontinuation of treatment in only 6% of patients. This is not the case when the intraperitoneal route of carboplatin administration is used when indicated.

Autologous transplantation of adipose-derived stem cells enhances skin graft survival and wound healing in diabetic rats.

BackgroundDiabetes can lead to impaired wound healing and skin grafts used surgically for diabetic wounds are often complicated with necrosis, although different therapies have been proposed. Adipose-derived stem cells (ASCs) participate in tissue repair processes and may have a role during impaired wound healing. In this study, autologous transplantation of ASCs was used to determine if it increases angiogenesis and skin graft survival and enhances wound healing in diabetic rats. MethodsAdipose-derived stem cells were successfully isolated and cultured. A full-thickness skin graft model was used to determine the effects of locally administered ASCs in 10 rats rendered diabetic (group 1), whereas 10 others served as controls (group 2). Histological examination of skin grafts followed after 1 week. Additionally, immunohistochemical staining intensity of vascular endothelial growth factor (VEGF) and transforming growth factor &bgr;3 (TGF-&bgr;3) was assessed in all grafts. ResultsThe gross and histological results showed significantly increased survival, angiogenesis, and epithelialization. Mean area of graft necrosis was significantly less in group 1 than in group 2 (7.49% vs 39.67%, P < 0.001). Statistically significant increase of capillary density, collagen intensity, VEGF, and TGF-&bgr;3 expression was noted in group 1 compared with group 2. ConclusionsThese findings suggest that autologous ASC transplantation can enhance skin graft survival in diabetic rats through differentiation, vasculogenesis, and secretion of growth factors such as VEGF and TGF-&bgr;3. This might represent a novel therapeutic approach in skin graft surgery for diabetic wounds.

Efficacy and safety of laparoscopic mini gastric bypass. A systematic review

BACKGROUND Laparoscopic mini-gastric bypass (LMGB) is a relatively new bariatric procedure; published studies are accumulating in various settings. The objective of this study was to summarize the available evidence about the efficacy and safety of LMGB. METHODS A systematic search in the literature was performed , and PubMed and reference lists were scrutinized (end-of-search date: July 15, 2013). For the assessment of the eligible articles, the Newcastle-Ottawa quality assessment scale was used. RESULTS Ten eligible studies were included in this study, reporting data on 4,899 patients. According to all included studies, LMGB induced substantial weight and body mass index reduction, as well as substantial excess weight loss. Moreover, resolution or improvement in all major associated medical illnesses and improvement in overall Gastrointestinal Quality of Life Index score were recorded. Major bleeding and anastomotic ulcer were the most commonly reported complications. Readmission rate ranged from 0%- 11%, whereas the rate of revision operations ranged from .3%- 6%. The latter were conducted due to a variety of medical reasons such as inadequate or excessive weight loss, malnutrition, and upper gastrointestinal bleeding. Finally, the mortality rate ranged between 0% and .5% among primary LMGB procedures. CONCLUSION LMGB represents an effective bariatric procedure; its safety and minimal postoperative morbidity seem remarkable. Randomized comparative studies seem mandatory for the further evaluation of LMGB.

Morbid Obesity and Sleeve Gastrectomy: How Does It Work?

Laparoscopic sleeve gastrectomy is known to be a safe and effective procedure for treating morbid obesity and is performed with increasing frequency both in Europe and the USA. Despite its broad use, many questions about the remaining gastric tube diameter, its long-term efficacy, its effects on gastric emptying, and the hormones involved still remain to be answered. In order to use such a relatively new surgical procedure wisely, it is essential for every surgeon and physician to understand how sleeve gastrectomy acts in obesity and what its potential benefits on the patients’ metabolism are. This review focuses on the most important pathophysiologic questions referred to sleeve gastrectomy on the literature so far, in an attempt to evaluate the different issues still pending on the subject.

Improvement of skin-graft survival after autologous transplantation of adipose-derived stem cells in rats

BACKGROUND Skin grafts are frequently used for a variety of indications in plastic and reconstructive surgery. Their necrosis is a common complication, while different therapies have been proposed. Currently, adipose-derived stem cells (ASCs) hold great promise for their angiogenic potential and role during tissue repair. In this study, autologous transplantation of ASCs was used in skin grafts in rats to determine if it increases angiogenesis, skin-graft survival and wound healing. METHODS ASCs were isolated, cultured, labelled with fluorescent dye and injected under full-thickness skin grafts in 10 rats (group 1), while 10 others served as controls (group 2). Skin grafts were analysed after 1 week. Collagens framework was assessed with Massons trichrome stain and angiogenesis with von Willebrand factor (vWF) immunohistochemistry. In addition, immunohistochemical staining intensity of vascular endothelial growth factor (VEGF) and transforming growth factor b3 (TGFb3) was assessed in all grafts. RESULTS Mean area of graft necrosis was significantly less in group 1 than in group 2 (6.12% vs. 32.62%, p<0.01). Statistically significant increase of microvessel density, collagen density, VEGF and TGFb3 expression was noted in group 1 compared with group 2 (all: p<0.01). CONCLUSIONS These findings suggest that autologous ASCs transplantation increases full-thickness skin-graft survival and shows promise for use in skin-graft surgery. This might be both due to in situ differentiation of ASCs into endothelial cells and increased secretion by ASCs of growth factors, such as VEGF and TGFb3 that enhance angiogenesis and wound healing.

Strong association of interleukin-6 -174 G>C promoter polymorphism with increased risk of oral cancer.

In view of the recently found contribution of factors associated with thrombosis and inflammation to carcinogenesis, we investigated the possible association of interleukin-6 (IL-6) with an increased risk of oral cancer. In DNA samples of 162 patients with oral squamous cell carcinoma and 156 healthy controls of comparable ethnicity, age and sex, we studied the -174 G>C polymorphism in the IL-6 gene, which affects its transcription. C allele frequencies were significantly increased in patients compared to controls, 42.6% versus 23.1% (p<0.001). The CC homozygotes had a 7-fold greater risk of developing oral cancer (odds ratio 7.39, 95% CI 2.61-20.92), while the GC heterozygotes had a 4-fold greater risk (odds ratio 3.74, 95% CI 2.29-6.11). A significant increase in C alleles was observed in patients regardless of their smoking or alcohol consumption habits, early or advanced stage of cancer, and presence or absence of a family history for cancer or thrombophilia (p<0.001; Fishers exact test). These findings suggest that the -174 G>C polymorphism, by affecting IL-6 gene expression, is strongly associated with oral oncogenesis.

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.

CYP2E1 and risk of chemically mediated cancers

Importance of the field: Among various human CYPs, CYP2E1 is of particular interest because of its involvement in the metabolic activation of many low molecular mass procarcinogens. CYP2E1 induction, which may be a consequence of genetic polymorphism or/and gene induction by xenobiotics, is the first step leading to the development of certain chemically-mediated cancers. The aim of this review is to outline the current knowledge on chemically-induced cancers through activation by CYP2E1, with emphasis on the association between polymorphisms of the CYP2E1 gene and incidence of different neoplasias. Areas covered in this review: Literature searches of MEDLINE (1966 to July 2009) for English articles in CYP2E1-induced carcinogenesis were conducted. What the reader will gain: CYP2E1 genetic polymorphisms leading to enhanced CYP2E1 gene transcription have been associated with increased risk of development of malignant tumours, through increased biotransformation of procarcinogens. Likewise, long-term intake of CYP2E1 inducers, such as ethanol, isoniazid, various solvents and chemicals, also increase the probability of developing malignancy, especially for carriers of certain CYP2E1 alleles. Take home message: Genetic screening for CYP2E1 ‘carcinogenic’ polymorphisms and CYP2E1 phenotype determination of susceptible subjects, as well as the development of effective CYP2E1 inhibitors, could be a future perspective towards prevention of CYP2E1-mediated cancers.

Expression of nuclear factor κB in human gastric carcinoma: relationship with IκBa and prognostic significance

Nuclear factor (NF)-κB is a transcription factor constitutively activated in various neoplasms, including gastric carcinoma. However, its clinical significance in the latter remains an unresolved issue, as published information is limited and controversial. Furthermore, no data is available about the interaction of NFκB with its inhibitory protein IκBa in gastric carcinoma cases. In this study, the expression of NFκB1/p50 and pIκBa protein was evaluated immunohistochemically in paraffin-embedded tissues from 93 patients. The effect of NFκB1/p50 and pIκBa on clinical outcome was assessed. Positive immunostaining was detected for nuclear NFκB1/p50, cytoplasmic NFκB1/p50 and pIκBa in 91, 68 and 85.7% of cases, respectively. A positive correlation emerged between nuclear NFκB1/p50 and pIκBa (p < 0.0001) and a negative one between cytoplasmic NFκB1/p50 and pIκBa (p = 0.0033). Nuclear NFκB1/p50 was associated with stage (p = 0.0388), the depth of invasion (p = 0.0382), World Health Organization (WHO; p = 0.0326) and Lauren’s histological classification (p = 0.0046). NFκB1/p50 nuclear expression adversely affected survival in both univariate and multivariate analysis (p < 0.0001 and p = 0.02, respectively). Our results suggest that NFκB1/p50 nuclear expression and therefore activation is regulated by its interaction with IκBa and that the former may serve as a useful independent molecular marker for stratifying patients with gastric carcinoma in terms of prognosis.