Microwave versus saline-linked radiofrequency (Aquamantys) assisted liver resection in a porcine liver resection model. A safety and feasibility pilot study.

PURPOSE: The aim of this study was to compare the feasibility, efficacy and safety of microwave ablation and saline-linked radiofrequency (Aquamantys) in liver resection. METHODS: Sixteen domestic pigs (8 per group) underwent thermoablations. Group A consisted of 8 pigs in which microwave left lateral liver resection was performed. Group B consisted of 8 pigs which underwent left lateral liver resection by the Aquamantys system. After 28 days of close follow-up, the animals were sacrificed in order to study the macroscopic and microscopic findings of each intervention on the liver edge. RESULTS: An average of 47.13 min was enough for the entire operation to take place using Aquamantys, whereas an average of 59.13 min was needed in the microwave liver resection group. Mean blood loss was 40 ml (range 5-85) with Aquamantys whereas mean blood loss was 72.37 ml (range 42-100) using microwave. Postoperative complications rates were extremely low in both groups. There was no intra- or postoperative mortality. CONCLUSIONS: Our study demonstrated that left lateral liver resection using Aquamantys system is technically feasible in the porcine model and proved to be highly effective and a safer hemostatic method compared to microwave ablation.

An overview of laparoscopic techniques in abdominal aortic aneurysm repair.

BACKGROUND: Since 1993, various laparoscopic techniques have been developed to make laparoscopic treatment of abdominal aortic aneurysms (AAAs) a possible therapeutic alternative. We aim to review all published clinical studies on laparoscopic surgery of AAAs and juxtarenal abdominal aortic aneurysms (JAAAs). METHODS: A thorough search of English-language literature published between January 1966 and December 2012 was performed. Studies that reported the results of laparoscopic surgical procedures as the intended repair strategy in patients with AAAs and JAAAs were selected using specific inclusion criteria. Only case series containing more than five patients were included. Outcome measures of eligible studies were extracted, tabulated, and then analyzed cumulatively, using a purely descriptive approach. RESULTS: Fourteen studies were included in the analysis encompassing 933 patients with AAAs (mean age, 68.5 years; age range, 46-88) averaging 55.8 mm in diameter and 96 patients with JAAAs (mean age, 71 years; age range, 50-81) averaging 57 mm in diameter. The mean follow-up was 15.3 months for the AAA cases and 32.8 months for the JAAA cases. Hand-assisted laparoscopy, in particular, had a low 30-day mortality rate, short cross-clamping and operative times, few perioperative and postoperative complications, high graft patency rates, and short length of both hospital and intensive care unit stay. CONCLUSIONS: Laparoscopic surgical procedures are a safe, feasible, and worthwhile alternative for patients with AAAs and JAAAs. Hand-assisted laparoscopy, in particular, was associated with low morbidity and mortality and short hospital and intensive care unit stay. However, the final decision regarding the best laparoscopic treatment should be left to the surgeon because of the limits of the data.

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

BACKGROUND: Diabetes 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. METHODS: Adipose-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 ß3 (TGF-ß3) was assessed in all grafts. RESULTS: The 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-ß3 expression was noted in group 1 compared with group 2. CONCLUSIONS: These 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-ß3. This might represent a novel therapeutic approach in skin graft surgery for diabetic wounds.

Staple line reinforcement in laparoscopic bariatric surgery: does it actually make a difference? A systematic review and meta-analysis.

BACKGROUND: Staple line leaks represent a major concern in all laparoscopic operations but are particularly important in bariatric surgery, where leak complications carry significant morbidity and mortality. Therefore, several means of staple line reinforcement have been described, but none is totally accepted. In this study, we attempt to illuminate any clear benefit of staple line reinforcement through a systematic review and meta-analysis of reported articles. METHODS: Two major databases (PubMed and Cochrane) were searched and assessed by two reviewers. Inclusion criteria were: detailed description of operative technique, especially concerning staple line reinforcement, and possible existence of proven staple line leak. Selected studies were evaluated by systematic review and meta-analysis according to their eligibility. The study population was finally divided into two groups: reinforcement (of any type) and no reinforcement. RESULTS: In the initial search, 126 studies were obtained. Then, 17 full papers, both randomised controlled trials (RCTs) and non-RCTs, were included in the systematic review. Seven studies, comprising 3,299 patients, were examined for evaluation of population odds of leak (7.69), which was considered clinically significant. Meta-analysis of three studies comprising 1,899 patients revealed no clear benefit of reinforcement group, though with marginal significance. CONCLUSIONS: Although several drawbacks exist, this study illustrates two important aspects: that current staplers may not be uniformly reliable, and that staple line reinforcement does not seem to have any clear benefit, at least concerning leak rate.

Laparoscopic adrenalectomy: where do we stand now?

Laparoscopic adrenalectomy (LA) has become the procedure of choice for the surgical removal of the vast majority of small sized adrenal tumors (

Clinical features of hypersensitivity reactions to oxaliplatin: a 10-year experience.

BACKGROUND: Oxaliplatin has become one of the major cytotoxic agents for the treatment of gastrointestinal tumors. As a result, several cases of the so-called oxaliplatin-associated hypersensitivity reaction have been documented. PATIENTS AND METHODS: We have retrospectively evaluated and characterized these reactions in our patient group by reviewing the files of 1,224 patients exposed to an oxaliplatin-containing regimen in order to provide useful clinical information for diagnosis and management. RESULTS: Three hundred and eight (308) patients who have never been exposed to platinum compounds developed symptoms compatible with a reaction to oxaliplatin that was verified by manifestation of at least similar symptoms on rechallenging. The reactions occurred after the first 5 courses, with a median course number of 9 (range 1-24). These reactions could be distinguished as (1) mild reactions occurring in 195 (63%) patients manifesting with itching and small area erythema either during treatment or within the next hours, and (2) severe reactions occurring in 113 (37%) patients within minutes of drug infusion manifesting with diffuse erythroderma, facial swelling, chest tightness, bronchospasm and changes in blood pressure. Oxaliplatin withdrawal was not required in patients with a mild reaction. Forty-eight (42%) patients having a severe reaction with appropriate premedication and prolongation of the infusion duration could tolerate 2-4 subsequent courses. For the remaining 65 (58%) patients, oxaliplatin withdrawal was inevitable because of the very severe reactions occurring on rechallenging. In addition, 3 patients presented with thrombocytopenia and 3 others with hemolytic anemia, all reversible upon oxaliplatin discontinuation. CONCLUSIONS: Hypersensitivity reactions to oxaliplatin are underestimated. Although the reactions are not frequent during first courses, in extensively pretreated patients, they may become a serious problem. In the majority of patients, drug discontinuation might not be necessary. In patients manifesting a severe reaction, re-exposure to oxaliplatin should be considered only if the patient can tolerate the reaction and there has been clinical benefit from this therapy. Physicians and nursing staff should be aware of the risk and be well prepared.

Video-assisted lung resection using radiofrequency ablation in a porcine model.

BACKGROUND: The aim of this study was to assess the feasibility, efficacy, and safety of video-assisted lingula resection using radiofrequency ablation (RFA) with internally cooled electrodes in a porcine model. MATERIALS AND METHODS: Six domestic pigs underwent RFA-assisted thoracoscopic lingulectomy. RFA was the only aerostatic and hemostatic method applied throughout the operation. After 30 d, the animals were sacrificed for the study of the macroscopic and microscopic effects of the technique. RESULTS: No signs of pneumothorax, blood loss, or infection were observed up to 1 mo postoperatively. There was no mortality either during or after surgery. The histopathology of the lung revealed three clearly demarcated zone lesions. CONCLUSIONS: Our study demonstrates that thoracoscopic lingulectomy using RFA energy is technically feasible. RFA energy is an effective and safe aerostatic and hemostatic method in the porcine model.

Hybrid procedures in the treatment of thoracoabdominal aortic aneurysms: a systematic review.

PURPOSE: To summarize the existing evidence on the use of hybrid open/endovascular repair in patients with thoracoabdominal aortic aneurysms (TAAA). METHODS: A thorough search was performed of the English-language literature published between January 1999 and October 2008. Studies that reported the results of hybrid procedures as the intended repair strategy in patients with TAAAs were selected using specific inclusion criteria [TAAA diagnosis based on the modified Crawford classification, a minimum 1-month follow-up, and data available on patient demographics, technical success, 30-day mortality, follow-up length, and outcome (neurological deficit, renal impairment, and/or graft vessel patency)]. From 35 articles initially identified, 15 studies were included in the statistical analysis encompassing 108 patients (75 men; mean age 67.6 years) with TAAAs averaging 72.7 mm in diameter. The majority of patients had aneurysms classified as Crawford types I (n = 20), II (n = 39), or III (n = 29); there were 14 type IV and 6 type V. RESULTS: Technical success was achieved in 91.6% (n = 99) of the 108 patients. Nineteen (16.6%) primary endoleaks and 3 (2.7%) secondary endoleaks were reported. Elective 30-day mortality was 10.4% (n = 10), while total 30-day mortality, including emergency cases, was 14.8% (n = 16). Three (2.7%) patients developed some permanent neurological deficit; renal failure was reported in 12 (11.1%). The mean follow-up period was 10.6 months, during which 97% of the grafts remained patent. Overall follow-up mortality was 24.1% (n = 26). CONCLUSION: Hybrid open endovascular repair is a new therapeutic option with encouraging results for patients considered unfit for conventional open repair. However, further research is required to draw robust conclusions.

Fibrinolytic and coagulation pathways after laparoscopic and open surgery: a prospective randomized trial.

BACKGROUND: Tissue injury poses increased risk for postoperative thromboembolic complications. Laparoscopic surgery, by causing limited tissue injury, is associated with lower risk for thromboembolism than is open surgery. We conducted a prospective randomized study in order to detect potentially existing differences in activation of coagulation and fibrinolytic pathways between open and laparoscopic surgery. METHODS: Forty patients with chronic cholelithiasis were randomly assigned to undergo open (group A) or laparoscopic cholecystectomy (group B). Blood samples were taken preoperatively, at the end of the procedure, and at 24 and 72 h postoperatively. Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), platelets (PLT), soluble fibrin monomer complexes (F.S. test), fibrin degradation products (FDP), D-dimers (D-D), and fibrinogen (FIB) were measured and compared within each group and between groups: Thrombin-antithrombin complexes (TAT) and prothrombin fragments (F1 + 2) were measured at 24 and 72 h postoperatively. RESULTS: Demographics were comparable between groups. Immediately postoperatively, TAT and F1 + 2 were significantly higher in group A (p < 0.05). They also increased significantly postoperatively as compared with preoperative levels within each group (p < 0.05). D-dimers were significantly higher in group A (p < 0.01) immediately postoperatively. D-dimers also increased significantly postoperatively in group B as compared with preoperative levels (p < 0.001). FIB decreased slightly in both groups at 24 h postoperatively but there was a significant increase in group A (p < 0.01). Soluble fibrin monomer complexes (SFMC) were detected twice in group A and only once in group B. FDP levels over 5 µg/ml were detected more often in group A (p < 0.05). There was not any case of thromboembolism or abnormal bleeding. CONCLUSIONS: Open surgery leads to higher activation of the clotting system than do laparoscopic procedures. Although of a lower degree, hypercoagulability is still observed in patients undergoing laparoscopic surgery and therefore routine thromboembolic prophylaxis should be considered.

BCL-2, p53 and HLA-DR antigen expression in surgically treated parotid cancer patients.

Our objective was to investigate the prognostic significance of bcl-2 protein, p53 protein and HLA-DR antigen expression in a group of surgically treated parotid cancer patients. We studied bcl-2, p53 and HLA-DR immunohistochemical expression in paraffin-embedded surgically removed tissue specimens derived from 26 patients with parotid cancer and 9 patients with Warthin parotid tumors operated between 2000 and 2006 at the Hippokration Hospital of Athens. The staining results were correlated with the patients' clinicopathological characteristics and clinical outcome. Bcl-2 expression was associated with a significantly decreased survival in patients with advanced tumor stage (P = 0.04), high grade lesions (P = 0.02), or cervical node involvement (P = 0.03). Radiotherapy was associated with a significantly improved recurrence-free survival among patients with negative tumor staining for either bcl-2, or both HLA-DR and bcl-2 [HLA-DR(-)/Bcl-2(-)] (P = 0.04 for both comparisons). Classical clinicopathologic factors failed to show prognostic value both in the univariate and the multivariate analyses performed. Our results suggest that bcl-2 can be used to identify locally advanced or histologically aggressive tumors with a lower survival probability following the application of standard treatment modalities. Furthermore, bcl-2(+) patients should be considered for more aggressive adjuvant treatment protocols, since conventional radiotherapy often fails to decrease relapse rates in this setting of patients.

Malignant carcinoid tumor of the cystic duct: a rare cause of bile duct obstruction.

BACKGROUND: Carcinoid tumors of the extrahepatic biliary tree are extremely rare malignancies, accounting for 0.2%-2% of all gastrointestinal carcinoid tumors, while carcinoids of the cystic duct are an uncommon entity and an extremely unusual cause of bile duct obstruction. METHODS: After an extensive literature review, we retrospectively analysed 61 cases of carcinoid tumor of the biliary tree as well as one additional case of a 60-year-old female with symptoms and laboratory/imaging examination findings compatible with those of a malignant biliary tract obstruction. At laparotomy, resection of the gallbladder and common bile duct was performed. Histological study revealed a well-differentiated neuro-endocrine carcinoma of the cystic duct. The patient remained disease-free at 16 months. RESULTS: Our presentation is the seventh case reported in the world literature. Compared to cholangiocarcinoma, analysis of the reviewed group indicates an increased incidence of extrahepatic carcinoid tumors in younger persons along with a slight female predominance. Statistically, the most common anatomic location is the common bile duct, followed by the perihilar region and the cystic duct. Jaundice is the most common finding. Curative surgery was realized in the majority of cases and long-term disease-free survival was achieved when surgery was curative. CONCLUSIONS: Carcinoid tumors obstructing the biliary tree are extremely difficult to diagnose preoperatively, and nearly impossible to differentiate from non-neuroendocrine tumors. As surgery offers the only potential cure for both biliary carcinoids and cholangiocarcinoma, we recommend aggressive surgical therapy as the treatment of choice in every case of potentially resectable biliary tumor.

Platelet production and related pathophysiology in acute myelogenous leukemia at first diagnosis: prognostic implications.

Among various laboratory and clinical features megakaryocytopoiesis and platelet (PLT) counts have been previously insufficiently evaluated for their prognostic significance in acute myelogenous leukaemia (AML). We studied several clinical and laboratory features of 108 first diagnosed AML patients in relation with their prognosis. Patients with favourable prognostic features were excluded from the study. This study focused on the prognostic impact of PLT counts and related molecular biology in AML patients at initial diagnosis. In particular, the PLT counts were correlated with the endogenous production of thrombopoietin (TPO), c-mpl expression, CD34+ leukemic blast cell proportion, cytogenetics, and a prognostic correlation was established. We found that the most favorable prognosis appeared in the AML patient group with PLTs <25x10(9)/l and correlated to cytogenetic findings (normal or abnormal karyotypes), while by far the most unfavorable prognosis was found in the patient group with PLTs > or =130x10(9)/l independent of the corresponding cytogenetics. It was demonstrated that AML patients with normal or elevated PLT counts at first presentation, may constitute a distinct patient group with particular characteristics such as higher levels of endogenous TPO production, high expression of CD34+ leukemic blast cells, higher expression of c-mpl and consequently low response to chemotherapy and a very poor prognosis. These correlations between PLTs production (megakaryothrombopoiesis), TPO serum levels and TPO receptor (c-mpl) expression may help in the determination of risk-adapted AML patient groups and of targeted therapeutic strategies.

Circulating lymphangiogenic growth factors in gastrointestinal solid tumors, could they be of any clinical significance?

Metastasis is the principal cause of cancer mortality, with the lymphatic system being the first route of tumor dissemination. The glycoproteins VEGF-C and VEGF-D are members of the vascular endothelial growth factor (VEGF) family, whose role has been recently recognized as lymphatic system regulators during embryogenesis and in pathological processes such as inflammation, lymphatic system disorders and malignant tumor metastasis. They are ligands for the VEGFR-3 receptor on the membrane of the lymphatic endothelial cell, resulting in dilatation of existing lymphatic vessels as well as in vegetation of new ones (lymphangiogenesis). Their determination is feasible in the circulating blood by immunoabsorption and in the tissue specimen by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Experimental and clinicopathological studies have linked the VEGF-C, VEGF-D/VEGFR3 axis to lymphatic spread as well as to the clinical outcome in several human solid tumors. The majority of these data are derived from surgical specimens and malignant cell series, rendering their clinical application questionable, due to subjectivity factors and post-treatment quantification. In an effort to overcome these drawbacks, an alternative method of immunodetection of the circulating levels of these molecules has been used in studies on gastric, esophageal and colorectal cancer. Their results denote that quantification of VEGF-C and VEGF-D in blood samples could serve as lymph node metastasis predictive biomarkers and contribute to preoperative staging of gastrointestinal malignancies.

Apolipoprotein J and leptin levels in patients with coronary heart disease.

BACKGROUND: Preliminary data suggest that apolipoprotein J (ApoJ) may play a role in the development and progression of atherosclerosis. Leptin, an adipose tissue hormone, exerts important cardiovascular effects. The association between serum ApoJ and leptin concentrations was assessed in patients with established or suspected coronary heart disease (CHD). PATIENTS AND METHODS: Serum ApoJ and leptin concentrations were evaluated in 67 CHD patients undergoing coronary angiography [54 individuals with significant (> or =50%) coronary artery stenosis and 13 patients without significant coronary artery stenosis on angiography]. RESULTS: Serum ApoJ concentrations in patients with significant coronary artery stenosis were significantly higher than in those without (303.9+/-118.6 vs. 121.2+/-37.5 microg/mL, respectively; p<0.001). The reverse pattern was observed for serum leptin levels (8.6+/-5.5 vs. 20.6+/-17.1 ng/ml, respectively; p=0.016). There was a significant negative correlation between ApoJ and leptin levels (r=-0.353; p=0.003). CONCLUSION: ApoJ and leptin may be markers for CHD.

Percutaneous cholecystostomy without interval cholecystectomy as definitive treatment of acute cholecystitis in elderly and critically ill patients.

OBJECTIVE: The aim of this study was to evaluate the safety and effectiveness of percutaneous cholecystostomy without interval cholecystectomy as definitive treatment for acute cholecystitis in elderly or critically ill patients with various coexisting diseases who were unfit for surgery under general anesthesia. DESIGN: Between July 2004 and June 2006, 24 consecutive elderly and critically ill patients unfit for surgery, suffering from acute cholecystitis, and in whom significant comorbid factors were present, underwent percutaneous cholecystostomy as an emergency procedure at Laiko General Hospital. The diagnosis and the severity of acute cholecystitis were based on the Tokyo Guidelines, whereas the American Society of Anesthesiologists' (ASA) physical status classification was used for the perioperative risk stratification for cholecystectomy. RESULTS: There were 14 male and 10 female patients with a median age of 79 years. Acute cholecystitis was classified as grade 2 in 20 patients and as grade 3 in 4 patients; 17 patients were classified as ASA score III and 7 as ASA score IV, whereas a total of 52 comorbid factors were present. Gallstones were disclosed as the underlying etiology in 23 patients, whereas one patient was diagnosed as suffering from acalculous cholecystitis. Percutaneous cholecystostomy was technically feasible in all patients (100%). Clinical improvement was noticed in 14 patients within 24 hours and in all patients within 72 hours. Statistically significant reduction in the values of white blood cells, C-reactive protein, and axillary body temperature were observed within 72 hours. The procedure-related mortality was 4%, whereas within a median follow-up of 17.5 months, definitive and effective control of symptoms was achieved in 90.5% of the patients. CONCLUSIONS: For the subgroup of extremely high-risk and unfit for surgery patients, percutaneous cholecystostomy might be considered as the definitive treatment since it controls the local symptoms and the systemic inflammatory response.

Expression of nuclear factor kappaB in human gastric carcinoma: relationship with I kappaB a and prognostic significance.

Nuclear factor (NF)-kappaB 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 NF kappaB with its inhibitory protein I kappaB a in gastric carcinoma cases. In this study, the expression of NF kappaB 1/p50 and p I kappaB a protein was evaluated immunohistochemically in paraffin-embedded tissues from 93 patients. The effect of NF kappaB 1/p50 and p I kappaB a on clinical outcome was assessed. Positive immunostaining was detected for nuclear NF kappaB 1/p50, cytoplasmic NF kappa B1/p50 and p I kappaB a in 91, 68 and 85.7% of cases, respectively. A positive correlation emerged between nuclear NF kappa B 1/p50 and p I kappaB a (p < 0.0001) and a negative one between cytoplasmic NF kappaB 1/p50 and p I kappaB a (p = 0.0033). Nuclear NF kappaB 1/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). NF kappaB 1/p50 nuclear expression adversely affected survival in both univariate and multivariate analysis (p < 0.0001 and p = 0.02, respectively). Our results suggest that NF kappaB 1/p50 nuclear expression and therefore activation is regulated by its interaction with I kappaB a and that the former may serve as a useful independent molecular marker for stratifying patients with gastric carcinoma in terms of prognosis.

Outcome of Fowler-Stephens operation for undescended testes: an experimental study.

The aim of this study was the outcome of Fowler-Stephens (FS) operations in prepubertal Wistar rats. Thirty-two 30-day-old rats underwent laparoscopic FS procedures on the right testicles (8 of them formed the control group). Nine, 30, 70, and 90 days later we assessed the testes histologically and determined inhibin betaB serum concentrations; 1 day earlier, ultrasonography was also performed. Decreases in central testicular vascularity and heterogeneous parenchymal echogenicity were the initial sonographic evidence of testicular damage, which either regressed in time or extended toward the periphery. Early degenerative changes either remained mild and restricted in the germinative epithelium or became more severe, affecting additional structures. Decreases in the seminiferous tubule area, thickening of the tunica albuginea, and increases in the number of mast cells were changes that reached significance. Significant decreases in the amount of serum inhibin betaB were also found, and the decreases correlated significantly with both the thickening of the tunica albuginea and the increases in the number of mast cells but not with the decreases in the seminiferous tubule area. Division of the spermatic vessels caused severe testicular degeneration as evidenced by changes in ultrasonographic and histologic features combined with drops in the levels of serum inhibin betaB.

Heterozygosity for interleukin-18 -607 A/C polymorphism is associated with risk for colorectal cancer.

BACKGROUND: The possible contribution of interleukin-18 (IL-18) -607 A/C polymorphism towards the development of colorectal cancer was investigated. PATIENTS AND METHODS: DNA samples of 84 patients with colorectal cancer (adenocarcinomas) and 89 healthy controls were examined by allele-specific polymerase chain reaction followed by electrophoretic analysis. The resulting allele and genotype frequencies of patients were compared to those of the respective controls using Fischer's exact test and odds ratios. RESULTS: The proportion of heterozygotes in the patient group was significantly higher than that in healthy controls (p < 0.01). This significant increase was detected independently of Dukes' tumor stage. Additionally, the carrier frequency of the mutant A allele was significantly higher in the patient group compared to controls (p < 0.05). CONCLUSION: The results indicate that heterozygotes for the IL-18 -607 A/C polymorphism exhibit increased risk for colorectal cancer development.

Genetic association studies in digestive system malignancies.

The multifactorial process of carcinogenesis in the digestive system involves mutations in oncogenes or tumor suppressor genes, as well as influence of environmental etiological factors. In recent years, common DNA polymorphisms in low penetrance genes emerged as genetic factors that seem to modulate an individual's susceptibility to malignancy, through interaction with environmental factors, such as diet or smoking. The increasing number of publications of genetic association studies on digestive system neoplasias has produced both important true association results and negative or controversial results. Here, we review the findings of genetic association studies of gene polymorphisms in regard to cancers of the digestive tract (oral, esophageal, nasopharyngeal, gastric and colorectal). We discuss the association of several DNA polymorphisms in genes of cytokines, matrix metalloproteinases, signal transduction proteins, diet-, and coagulation-related factors with specific types of cancer in the digestive tract. Genetic studies, which lead to a true association, are expected to increase understanding of the pathogenesis of each malignancy and to be a powerful tool of prevention and prognosis in the future.

Paclitaxel-ifosfamide-cisplatin as salvage chemotherapy in ovarian cancer patients pretreated with platinum compounds and paclitaxel.

BACKGROUND: The role of combination chemotherapy regimens in the management of ovarian cancer patients with tumors previously exposed to platinum compounds and paclitaxel has not yet been defined. The present phase II study evaluated the activity and toxicity of a paclitaxel-ifosfamide-cisplatin combination in the aforementioned group of patients. Given the in vitro and in vivo synergism between these three agents, it was believed that using a three drug combination would overcome tumor resistance to cisplatin. PATIENTS AND METHODS: Thirty-five patients were enrolled in the study. The median age was 55 and the median performance status 1. Thirteen (37%) had potentially platinum sensitive, 12 (35%) had primary platinum-resistant and 10 (28%) patients had secondary platinum-resistant tumors. Treatment consisted of paclitaxel 175 mg/m2 as a 3 h i.v. infusion on day 1, cisplatin 75 mg/m2 i.v. over 2 h fractionated over days 1 and 2, and ifosfamide 5 mg/m2 i.v. over 1 h fractionated on days 1-2 with mesna uroprotection. Courses were administered every 3 weeks on an outpatient basis. Granulocyte-colony stimulation factor (G-CSF) was given at a dose of 5 microg/kg/day on days 4-10. A median of 4 cycles were administered with the delivered dose intensity at 85% of the planned dose for the three agents. RESULTS: Among 35 patients evaluable for response and toxicity, there were 10 partial responses with a response rate of 28.6% (95% confidence interval 12%-45%). Stable disease was recorded in 9 (25.7%) and progressive disease in 16 (45.7%) patients. Subgroup analysis revealed a response rate of 38.5% in potentially platinum-sensitive, 16.5% in primary platinum-resistant and 30% in secondary platinum-resistant tumors. The median response duration was 5 months (range 3-14 months), the median time to progression 6 months (range 3-18 months) and the median survival 12 months (range 3-44 months). Myelotoxicity was significant with neutropenia grade 3 and 4 occurring in 35% and 45% of patients, respectively. Eight episodes (5% of all cycles) of febrile neutropenia were documented and well managed with oral or i.v. antibiotics and G-CSF continuation until complete recovery. Grade 1, 2 and 3 peripheral neuropathy developed in 30%, 30% and 10% of patients, respectively. In conclusion, the three drug combination demonstrated a significant effectiveness in potentially platinum-sensitive tumors and a moderate efficacy in platinum-resistant tumors. The regimen, although myelotoxic, is tolerable with G-CSF support. Further investigation via comparative studies is required to define any superiority of the present regimen over doublets of the three agents in this group of patients.