LACC Trial: Final Analysis on Overall Survival Comparing Open Versus Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The aim of this study was to compare overall survival between open and minimally invasive radical hysterectomy with participants followed for 4.5 years. The primary objective was to evaluate whether minimally invasive surgery was noninferior in disease-free survival (DFS) to abdominal radical hysterectomy. Secondary outcomes included overall survival. Sample size was based on DFS of 90% at 4.5 years and 7.2% noninferiority margin for minimally invasive surgery. A total of 631 patients were enrolled: 319 assigned to minimally invasive and 312 to open surgery. Of these, 289 (90.6%) patients underwent minimally invasive surgery and 274 (87.8%) patients open surgery. At 4.5 years, DFS was 85.0% in the minimally invasive group and 96% in the open group (difference of -11.1; 95% CI, -15.8 to -6.3; P = .95 for noninferiority). Minimally invasive surgery was associated with lower rate of DFS compared with open surgery (hazard ratio [HR], 3.91 [95% CI, 2.02 to 7.58]; P < .001). Rate of overall survival at 4.5 years was 90.6% versus 96.2% for the minimally invasive and open surgery groups, respectively (HR for death of any cause = 2.71 [95% CI, 1.32 to 5.59]; P = .007). Given higher recurrence rate and worse overall survival with minimally invasive surgery, an open approach should be standard of care.

Recommendations for the treatment of vulvar cancer in settings with limited resources: Report from the International Gynecological Cancer Society consensus meeting.

Introduction: Due to scant literature and the absence of high-level evidence, the treatment of vulvar cancer is even more challenging in countries facing limited resources, where direct application of international guidelines is difficult. Recommendations from a panel of experts convened to address some of these challenges were developed. Methods: The panel met in Rio de Janeiro in September 2019 during the International Gynecological Cancer Society congress and was composed of specialists from countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East. The panel addressed 62 questions and provided recommendations for the management of early, locally advanced, recurrent, and/or metastatic vulvar cancer. Consensus was defined as at least 75% of the voting members selecting a particular recommendation, whereas a majority vote was considered when one option garnered between 50.0% and 74.9% of votes. Resource limitation was defined as any issues limiting access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or funding for the provision of contemporary medical care. Results: Consensus was reached for nine of 62 (14.5%) questions presented to the panel, whereas a majority vote was reached for 29 (46.7%) additional questions. For the remaining questions, there was considerable heterogeneity in the recommendations. Conclusion: The development of guidelines focusing on areas of the world facing more severe resource limitations may improve medical practice and patient care.

Recommendations for the prevention, screening, diagnosis, staging, and management of cervical cancer in areas with limited resources: Report from the International Gynecological Cancer Society consensus meeting.

Introduction: Nearly 85% of cervical cancer new cases are diagnosed in limited resources countries. Although several strategies have been proposed to reduce the disease burden, challenges remain to provide the best possible care. We report recommendations from an expert consensus meeting convened to address from prevention to management of cervical cancer in limited resources countries. Methods: The expert panel, composed by invited specialists from 38 developing countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East, convened in Rio de Janeiro in September 2019, during the Global Meeting of the International Gynecological Cancer Society (IGCS). Panel members considered the published scientific evidence and their practical experience on the topics, as well as the perceived cost-effectiveness of, and access to, the available interventions. The focus of the recommendations was on geographic regions rather than entire countries because medical practice varies considerably in the countries represented. Resource limitation was qualified as limited access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or overall funding for provision of state-of-the-art care. Consensus was defined as at least 75% of the voting members selecting a particular answer of the multiple-choice questionnaire, whereas the majority vote was considered as 50% to 74.9%. Results: Consensus was reached for 25 of the 121 (20.7%) questions, whereas for 54 (44.6%) questions there was one option garnering between 50% to 74.9% of votes (majority votes). For the remaining questions, considerable heterogeneity in responses was observed. Discussion: The implementation of international guidelines is challenging in countries with resource limitations or unique health-care landscapes. The development of guidelines by the health care providers in those regions is more reflective of the reality on the ground and may improve medical practice and patient care. However, challenges remain toward achieving that goal at political, economic, social, and medical levels.

Interest In and Practices Related to Gynecologic Oncology among Members of the Brazilian Federation of Associations of Gynecology and Obstetrics.

OBJECTIVE: The present study aims to obtain basic demographic information, the level of interest and of training in gynecology oncology among Brazilian obstetricians and gynecologists (OB-GYNs) to create a professional profile. METHODS: An online questionnaire was sent to 16,008 gynecologists affiliated to the Brazilian Federation of Associations of Gynecology and Obstetrics (FEBRASGO, in the Portuguese acronym). We considered gynecologists dedicated to gynecologic oncology (OB-GYNs ONCO) those who self-reported that > 50% of their daily practice consists in working with women's cancer care. RESULTS: A total of 1,608 (10%) of 16,008 FEBRASGO members responded. The OB-GYNs are concentrated in the southern and southeastern states of Brazil. Gynecologic oncology was considered the 8th greatest area of interest in gynecology among the OB-GYNs. A total of 95 (5.9%) of the OB-GYNs were considered OB-GYNs ONCO. Obstetricians and gynecologists are actively engaged in cancer care: > 60% of them dedicate up to 25% of their daily practice to oncology. The role of the physicians in screening and prevention, diagnosis, in the treatment of precancerous lesions, and in low complexity surgical procedures is notably high. Gynecologists dedicated to gynecologic oncology in Brazil have a heterogeneous, nonstandardized and short training period in gynecologic oncology. These professionals had a more significantly role in performing medium- and high-complexity operations compared with OB-GYNs (65.2% versus 34%, and 47.3% versus 8.4%, respectively). CONCLUSION: The role of OB-GYNs and of OB-GYNs ONCO appears to be complementary. Obstetricians and gynecologists act more often in screening and prevention and in low-complexity surgical procedures, whereas OB-GYNs ONCO are more involved in highly complex cases. Strategies to raise standards in cancer training and to encourage the recognition of gynecologic oncology as a subspecialty should be adopted in Brazil.

OBJETIVO: O presente estudo tem como objetivo obter informações demográficas básicas, o nível de interesse e de treinamento em ginecologia oncológica entre obstetras e ginecologistas (OB-GYNs) brasileiros para criar um perfil destes profissionais. MéTODOS: Um questionário online foi enviado a 16.008 ginecologistas filiados à Federação Brasileira de Associações de Ginecologia e Obstetrícia (FEBRASGO). Nós consideramos ginecologistas dedicados à oncologia ginecológica (OB-GYNs ONCO) aqueles que referiram atuar em > 50% de sua prática diária com o tratamento do câncer feminino. RESULTADOS: Um total de 1.608 (10%) dos 16.008 membros da FEBRASGO responderam ao questionário. Os OB-GYNs estão concentrados nos estados do sul e sudeste do Brasil. A oncologia ginecológica foi considerada a 8ª área de maior interesse em ginecologia entre os OB-GYNs. Um total de 95 (5,9%) dos OB-GYNs foram considerados ginecologistas dedicados à oncologia ginecológica (OB-GYNs ONCO). Obstetras e ginecologistas estão ativamente envolvidos no tratamento do câncer: > 60% deles dedicam até 25% de sua prática diária à oncologia. O papel dos médicos na triagem e na prevenção, no diagnóstico, no tratamento de lesões pré-cancerosas e em procedimentos cirúrgicos de baixa complexidade é notavelmente alto. Ginecologistas dedicados à oncologia ginecológica no Brasil têm um período de treinamento em oncologia ginecológica heterogêneo, não padronizado e curto. Estes profissionais tiveram um papel mais significativo na realização de operações de média e alta complexidade em comparação com OB-GYNs (65,2% versus 34%, e 47,3% versus 8,4%, respectivamente). CONCLUSãO: Os papéis dos OB-GYN e dos OB-GYNs ONCO parecem ser complementares. Os OB-GYNs frequentemente atuam em triagem e prevenção e em procedimentos cirúrgicos de baixa complexidade, enquanto os OB-GYNs ONCO estão mais envolvidos em casos de mais alta complexidade. Estratégias para elevar os padrões de treinamento em oncoginecologia e incentivar o reconhecimento da oncologia ginecológica como uma subespecialidade devem ser adotadas no Brasil.

Interest in and practices related to gynecologic oncology among members of the Brazilian Federation of Associations of Gynecology and Obstetrics / Interesse e práticas relacionadas à oncologia ginecológica entre os membros da Federação Brasileira de Associações de Ginecologia e Obstetrícia

Abstract Objective The present study aims to obtain basic demographic information, the level of interest and of training in gynecology oncology among Brazilian obstetricians and gynecologists (OB-GYNs) to create a professional profile. Methods An online questionnaire was sent to 16,008 gynecologists affiliated to the Brazilian Federation of Associations of Gynecology and Obstetrics (FEBRASGO, in the Portuguese acronym). We considered gynecologists dedicated to gynecologic oncology (OB-GYNs ONCO) those who self-reported that > 50% of their daily practice consists in working with women's cancer care. Results A total of 1,608 (10%) of 16,008 FEBRASGO members responded. The OBGYNs are concentrated in the southern and southeastern states of Brazil. Gynecologic oncology was considered the 8th greatest area of interest in gynecology among the OBGYNs. A total of 95 (5.9%) of the OB-GYNs were considered OB-GYNs ONCO. Obstetricians and gynecologists are actively engaged in cancer care: > 60% of them dedicate up to 25% of their daily practice to oncology. The role of the physicians in screening and prevention, diagnosis, in the treatment of precancerous lesions, and in low complexity surgical procedures is notably high. Gynecologists dedicated to gynecologic oncology in Brazil have a heterogeneous, nonstandardized and short training period in gynecologic oncology. These professionals had a more significantly role in performing medium- and high-complexity operations compared with OB-GYNs (65.2% versus 34%, and 47.3% versus 8.4%, respectively). Conclusion The role of OB-GYNs and of OB-GYNs ONCO appears to be complementary. Obstetricians and gynecologists actmore often in screening and prevention and in low-complexity surgical procedures, whereas OB-GYNs ONCO are more involved in highly complex cases. Strategies to raise standards in cancer training and to encourage the recognition of gynecologic oncology as a subspecialty should be adopted in Brazil.

Resumo Objetivo Opresente estudotemcomo objetivo obter informações demográficas básicas, o nível de interesse e de treinamento em ginecologia oncológica entre obstetras e ginecologistas (OB-GYNs) brasileiros para criar um perfil destes profissionais. Métodos Umquestionário online foi enviado a 16.008 ginecologistas filiados à Federação Brasileira de Associações de Ginecologia e Obstetrícia (FEBRASGO). Nós consideramos ginecologistas dedicados à oncologia ginecológica (OB-GYNsONCO) aqueles que referiram atuar em > 50% de sua prática diária com o tratamento do câncer feminino. Resultados Um total de 1.608 (10%) dos 16.008 membros da FEBRASGO responderam ao questionário. Os OB-GYNs estão concentrados nos estados do sul e sudeste do Brasil. A oncologia ginecológica foi considerada a 8ª área de maior interesse em ginecologia entre os OB-GYNs. Um total de 95 (5,9%) dos OB-GYNs foram considerados ginecologistas dedicados à oncologia ginecológica (OB-GYNs ONCO). Obstetras e ginecologistas estão ativamente envolvidos no tratamento do câncer: > 60% deles dedicam até 25% de sua prática diária à oncologia. O papel dosmédicos na triageme na prevenção, no diagnóstico, no tratamento de lesões pré-cancerosas e em procedimentos cirúrgicos de baixa complexidade é notavelmente alto. Ginecologistas dedicados à oncologia ginecológica no Brasil têm umperíodo de treinamento emoncologia ginecológica heterogêneo, não padronizado e curto. Estes profissionais tiveram um papel mais significativo na realização de operações de média e alta complexidade em comparação com OB-GYNs (65,2% versus 34%, e 47,3% versus 8,4%, respectivamente). Conclusão Os papéis dos OB-GYN e dos OB-GYNs ONCO parecem ser complementares. Os OB-GYNs frequentemente atuam emtriageme prevenção e em procedimentos cirúrgicos de baixa complexidade, enquanto os OB-GYNs ONCO estão mais envolvidos em casos demais alta complexidade. Estratégias para elevar os padrões de treinamento em oncoginecologia e incentivar o reconhecimento da oncologia ginecológica como uma subespecialidade devem ser adotadas no Brasil.

hERG1 Channels and Glut-1 as Independent Prognostic Indicators of Worse Outcome in Stage I and II Colorectal Cancer: A Pilot Study.

BACKGROUND: There is a need to identify new markers to assess recurrence risk in early-stage colorectal cancer (CRC) patients. We explored the prognostic impact of ether-a-gò-gò-related gene 1 channels and some hypoxia markers, in patients with nonmetastatic (stage I, II, and III) CRC. METHODS: The expression of hERG1, vascular endothelial growth factor A (VEGF-A), glucose transporter 1, carbonic anhydrase IX (CA-IX), epidermal growth factor receptor (EGF-R), and p53 was tested by immunohistochemistry in 135 patients. The median follow-up was 35 months. Clinicopathologic parameters and overall survival were evaluated. RESULTS: hERG1 displayed a statistically significant association with Glut-1, VEGF-A, CA-IX, and EGF-R; p53 with VEGF-A and CA-IX; Glut-1 with the age of the patients; and EGF-R with TNM and mucin content. TNM and CA-IX were prognostic factors at the univariate analysis; TNM, hERG1, and Glut-1, at the multivariate analysis. Risk scores calculated from the final multivariate model allowed to stratify patients into four different risk groups: A) stage I-II, Glut-1 positivity, any hERG1; B) stage I-II, Glut-1 and hERG1 negativity; C) stage I-II, Glut-1 negativity, hERG1 positivity; D) stage III, any Glut-1 and any hERG1. CONCLUSIONS: hERG1 positivity with Glut-1 negativity identifies a patient group with poor prognosis within stage I-II CRC. The possibility that these patients might benefit from adjuvant therapy, independently from the TNM stage, is discussed. IMPACT: More robust prognostic and predictive markers, supplementing standard clinical and pathologic staging, are needed for node-negative patients.

Polymorphic DNA repair and metabolic genes: a multigenic study on gastric cancer.

Risk factors for gastric cancer (GC) include inter-individual variability in the inflammatory response to Helicobacter pylori infection, in the ability of detoxifying DNA reactive species and repairing DNA damage generated by oxidative stress and dietary carcinogens. To evaluate the association between polymorphic DNA repair genes and GC risk, a case-control study including 314 histologically confirmed GC patients and 548 healthy controls was conducted in a GC high-risk area in Tuscany, Italy. Polymorphic variants of base excision repair (APE1-D148E, XRCC1-R194W, XRCC1-R399Q and OGG1-S326C), nucleotide excision repair (XPC-PAT, XPA-23G>A, ERCC1-19007T>C and XPD-L751Q), recombination (XRCC3-T241M) and alkylation damage reversal (MGMT-L84F) were tested for their potential role in the development of GC by using logistic regression models. The same population was also characterised for GSTT1 and GSTM1 variant alleles to search for possible functional interactions between metabolic and DNA repair genotypes by two-way interactions using multivariate logistic models. No significant association between any single DNA repair genotype and GC risk was detected with a borderline association with the XPC-PAT homozygous genotype [odds ratio (OR) =1.42; 95% confidence interval (CI) 0.94-2.17]. Gene-gene interaction analysis revealed combinations of unfavourable genotypes involving either multiple DNA repair polymorphisms or DNA repair and GST-specific genotypes. The combination of the XPC-PAT and the XPA variant alleles significantly increased GC risk (OR=2.15; 95% CI 1.17-3.93, P=0.0092). A significant interaction was also found between the APE1 wild-type genotype and either the single GSTT1 (OR=4.90; 95% CI 2.38-10.11, P=0.0079) or double GSTM1-GSTT1 null (OR=7.84; 95% CI 3.19-19.22, P=0.0169) genotypes or the XPA-mutant allele (OR=3.56; 95% CI 1.53-8.25, P=0.0012). These findings indicate that a complex interaction between host factors such as oxidative stress, antioxidant capacity and efficiency of multiple DNA repair pathways underlies the inter-individual variability in GC risk.

Laparoscopic appendectomy performed by residents and experienced surgeons.

BACKGROUND: Laparoscopic appendectomy is widely performed by surgical residents, but its changing indications and outcomes have been poorly investigated. The aim of this study was to examine whether a difference exists in indications and outcomes between laparoscopic appendectomies performed by residents and those performed by experienced surgeons. METHODS: Between 1999 and 2007, 218 laparoscopic appendectomies were performed and recorded. Data were analyzed to compare operations performed by residents with those by experienced surgeons in terms of indications for surgery and severity of disease. Moreover, laparoscopic appendectomies were thoroughly compared regarding outcomes and complications. RESULTS: The residents had fewer conversions with laparoscopic appendectomy (8% vs 17%, P=0.04), and similar complication rates (12% vs 13%, P=0.16), compared with experienced surgeons. The median operating time was also comparable (67 minutes vs 60 minutes, P=0.23). However, patients operated on by residents had more emergencies (86% vs 70%, P=0.009), included more foreigners (27% vs 15%, P=0.03), and had intermediate to severe diseases, (81 vs 52%, P<0.001) than patients did operated on by experienced surgeons. CONCLUSIONS: Surgical residents performed more emergency laparoscopic appendectomies on foreign patients suffering from intermediate to severe diseases compared with experienced surgeons, with comparable surgical outcomes and lower conversion rates.

Comparison of laparoscopic and open repair for primary ventral hernias.

We designed a retrospective clinical trial comparing laparoscopic primary ventral hernia repair (LPVHR) and open traditional repair (OPVHR). Demographics, perioperative data, results, and follow-up were examined to determine if there was any difference in the main outcomes. From January 2000 to December 2006, 28 consecutive, unselected patients, who successfully underwent LPVHR, were matched with 36 patients, who received OPVHR (with mesh) during the same period. The operating room records, clinical files, and outpatient sheets were examined. Patient demographics, results, and follow-up were compared in the 2 groups. Demographic characteristics, site of hernia, concomitant surgery, and defect size were comparable between the 2 groups, but the proportion of urgent procedures was higher in OPVHR patients (25% vs. 4%; P=0.03). The overall complication rates were similar, with some specific differences, whereas analgesic requirement and hospital stay were also comparable. The operative times were significantly longer for the LPVHR group (70 min vs. 35 min; P<0.000). Four recurrences were noted in both OPVHR and LPVHR patients, 11% versus 14%, respectively, with no significant difference (P=0.67). LPVHR seemed to be as safe as the OVHR in this study, although LPVHR increased operative time. The complications of each method should be taken into consideration before making the choice of the surgical approach.

The CHOLEGAS study: multicentric randomized, blinded, controlled trial of gastrectomy plus prophylactic cholecystectomy versus gastrectomy only, in adults submitted to gastric cancer surgery with curative intent.

BACKGROUND: The incidence of gallstones and gallbladder sludge is known to be higher in patients after gastrectomy than in general population. This higher incidence is probably related to surgical dissection of the vagus nerve branches and the anatomical gastrointestinal reconstruction. Therefore, some surgeons perform routine concomitant cholecystectomy during standard surgery for gastric malignancies. However, not all the patients who are diagnosed to have cholelithiasis after gastric cancer surgery will develop symptoms or require additional surgical treatments and a standard laparoscopic cholecystectomy is feasible even in those patients who underwent previous gastric surgery. At the present, no randomized study has been published and the decision of gallbladder management is left to each surgeon preference. DESIGN: The study is a randomized controlled investigation. The study will be performed in the General and Oncologic Surgery, Department of Oncology-Azienda Ospedaliero-Universitaria Careggi-Florence-Italy, a large teaching institution, with the participation of all surgeons who accept to be involved in, together with other Italian Surgical Centers, on behalf of the GIRCG (Italian Research Group for Gastric Cancer).The patients will be randomized into two groups: in the first group the patient will be submitted to prophylactic cholecystectomy during standard surgery for curable gastric cancer (subtotal or total gastrectomy), while in the second group he/she will be submitted to standard gastric surgery only. TRIAL REGISTRATION: ClinicalTrials.gov ID. NCT00757640.

Predictors of recurrence after laparoscopic ventral hernia repair.

Laparoscopic ventral hernia repair (LVHR) is widely used to manage ventral hernias, but predictors of hernia recurrence have been poorly investigated. This retrospective study investigated the influence of common risk factors on hernia recurrence. Data from 146 consecutive, unselected patients who underwent LVHR between 2000 and 2006 were collected. Demographic, clinical, and perioperative parameters were analyzed to identify predictable risk factors for hernia recurrence. Both univariate and multivariate Cox's regression analysis were employed. The overall recurrence rate was 8% (12 patients) after an average follow-up of 45 months. On univariate analysis, smoking (P=0.01) and earlier repair (P<0.00) were significantly different in recurred patients. However, only earlier repair was an independent predictor of multivariate Cox's regression analysis (hazard ratio 0.085, 95% confidence interval: 0.020-0.355; P=0.001). LVHR is a safe technique to repair ventral hernias. However, smokers with earlier failed repair attempts have a higher risk of recurrence.

Characterization of tumor antigen peptide-specific T cells isolated from the neoplastic tissue of patients with gastric adenocarcinoma.

Gastric cancer is a significant cause of morbidity and mortality worldwide. Surgical resection remains the primary curative treatment for gastric adenocarcinoma, but the poor (15-35%) survival rate at 5 years has prompted many studies for new therapeutic strategies, such as specific immunotherapy. The aim of this study was to analyze the functional properties of the T cell response to different antigen peptides related to gastric cancer in patients with gastric adenocarcinoma. To this purpose, we have cloned and characterized tumor-infiltrating T cells (TILs) isolated from the neoplastic gastric tissue samples. A T cell response specific to different peptides of gastric cancer antigens tested was documented in 17 out of 20 patients, selected for their HLA-A02 and/or -A24 alleles. Most of the cancer peptide-specific TILs expressed a Th1/Tc1 profile and cytotoxic activity against target cells. The effector functions of cancer peptide-specific T cells obtained from the peripheral blood of the same patients were also studied. The majority of peripheral blood peptide-specific T cells also expressed the Th1/Tc1 functional profile. In conclusion, in most of the patients with gastric adenocarcinoma, a specific type-1 T cell response to gastric cancer antigens was detectable and would have the potential of hamper tumor cell growth. However, in order to get tumor cell killing in vivo, the activity and the number of cancer peptide-specific Th1/Tc1 cells probably need to be enhanced by vaccination with the appropriate cancer antigenic peptides or by injection of the autologus tumor peptide-specific T cells expanded in vitro.

The torsion of a wandering pelvic spleen: A case report.

A 15 years old patient was taken to the operative room for an explorative laparotomy due to abdominal pain and a pelvic spleen at preoperative computed tomography: was pointed out the absence of all splenic ligamentous attachments and short gastric vessels with a consequently dislocation of a bigger and congested spleen in the pelvis. This organ, wrapped in the omentum, was in a serious ischemic suffering due to a 720 degrees clock torsion around its exceptionally long pedicle (about 20 cm); besides was confirmed pancreatic body and tail ectopy. Following the derotation, the volume of the organ has decreased but became fixed in above norm dimensions. A total splenectomy was executed.

Safety of laparoscopic cholecystectomy performed by surgical residents.

Laparoscopic cholecystectomy is being widely performed by surgical residents, but specific outcomes have been poorly investigated. Data from 171 consecutive, unselected patients who underwent laparoscopic cholecystectomy performed by surgical residents were collected and matched with an equal number of randomly extracted laparoscopic cholecystectomies performed by experienced senior staff surgeons between 2000 and 2006 at our institution. Demographic data, emergency procedures, cholangiographies, complications and length of stay were not significantly different between the two groups. However, surgical residents performed the operations in less complicated patients (ASA group 3-4 2% vs. 8%, respectively, p = 0.04). Moreover, the median duration of surgery was significantly longer in the resident group (67 vs. 50 minutes, p < 0.001), with fewer additional contemporary procedures (3% vs. 7%, respectively, p = 0.009). This study established that although surgical residents operated on less complex patients with longer operative times, the intraoperative difficulties and main outcomes were the same as for the senior surgeons.

Acetaldehyde inhibits PPARgamma via H2O2-mediated c-Abl activation in human hepatic stellate cells.

BACKGROUND & AIMS: Accumulating evidence indicates that acetaldehyde (AcCHO) is one of the main mediators of fibrogenesis in alcoholic liver disease. AcCHO stimulates synthesis of fibrillar collagens in hepatic stellate cells, but the molecular events directly involved in the activation of collagen genes are debatable. METHODS: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that is expressed in stellate cells, and its activation by specific ligands inhibits collagen synthesis. In this study, we evaluated the effects of AcCHO on PPARgamma transcriptional activity and its correlation with the AcCHO-induced collagen synthesis in hepatic stellate cells. RESULTS: AcCHO treatment inhibited ligand-dependent and -independent PPARgamma transcriptional activity, and this effect was correlated with an increased phosphorylation of a mitogen-activated protein kinase site at serine 84 of the human PPARgamma. Transfection of the PPARgammaSer84Ala mutant completely prevented the effect of AcCHO on PPARgamma activity and in parallel abrogated the induction of collagen gene expression by AcCHO. The effect of AcCHO on PPARgamma activity and phosphorylation was blocked by extracellular signal-regulated kinase (ERK) 1/2 and protein kinase C (PKC)delta inhibitors as well as by catalase, suggesting that hydrogen peroxide is involved in the molecular cascade responsible for PPARgamma phosphorylation via activation of the PKCdelta/ERK pathway. Furthermore, inhibition of c-Abl completely abrogated the effect of AcCHO on either PPARgamma function or collagen synthesis; in addition, expression of the PPARgammaSer84Ala mutant prevented the profibrogenic signals mediated by c-Abl activation. CONCLUSIONS: Our results showed that the induction of collagen expression by AcCHO in stellate cells is dependent on PPARgamma phosphorylation induced by a hydrogen peroxide-mediated activation of the profibrogenic c-Abl signaling pathway.

Gastric duplication cyst in an adult: case report.

Duplication cysts of the stomach are uncommon findings in adult patients and diagnosis is often overlooked. Presenting symptoms are often non-specific, but complications, including chronic infections, ruptures or carcinoma arising in the cyst, are rare. We report a case of a non-communicating cyst of the stomach in a 67-year-old man.

herg1 gene and HERG1 protein are overexpressed in colorectal cancers and regulate cell invasion of tumor cells.

The acquisition of the capacity to invade surrounding tissues confers a more malignant phenotype to tumor cells and is necessary for the establishment of metastases. The understanding of the molecular mechanisms underlying cell invasion in human solid tumors such as colorectal cancers could provide not only more sensitive prognostic analyses but also novel molecular targets for cancer therapy. We report in this article that K(+) ion channels belonging to the HERG family are important determinants for the acquisition of an invasive phenotype in colorectal cancers. The herg1 gene and HERG1 protein are expressed in many colon cancer cell lines, and the activity of HERG channels modulates colon cancer cell invasiveness. Moreover, the amount of HERG1 protein expressed on the plasma membrane is directly related to the invasive phenotype of colon cancer cells. Finally, both the herg1 gene and HERG1 protein were expressed in a high percentage of primary human colorectal cancers, with the highest incidence occurring in metastatic cancers, whereas no expression could be detected either in normal colonic mucosa or in adenomas.

[Experience with and results of the laparoscopic treatment of laparocele]. / Esperienza e risultati nel trattamento laparoscopico dei laparoceli.

The purpose of this study was to describe our experience from December 1999 to March 2003 with a series of 76 cases of laparocele, 56 of which (74%) were incisional and 26 (26%) primitive. The case series shows a prevalence of the female sex (2/1) and in 18% of cases the patients were obese (BMI > or = 30). The mean corrected surface was 71 cm2 +/- 75 SD (10-260). The technique requires the use of an open access ePTFE dual mesh prosthesis with micropores. The mean operating time was 102 min +/- 38 SD (40-240). In 5 cases (6.5%) an open conversion was necessary owing to visceral lesions. Minor complications were observed in 19 patients (25%), who were treated in the early period of our experience. Among the most important complications was one late bowel perforation (1%) that required immediate laparoscopic reoperation. The mean hospital stay was 4 days +/- 2 SD (1-13), although now that a certain amount of experience has been acquired, the mean stay in hospital is only 2 days. The follow-up of 16 months +/- 3 SD (2-36) has revealed 3 recurrences (4%) and 1 trocar herniation (1%).

Laparoscopic cholecystectomy: retrospective comparative evaluation of titanium versus absorbable clips.

We present a retrospective study of the use of titanium and absorbable clips during laparoscopic cholecystectomy. The aim was to determine any differences in outcome and costs. From January 1999 to February 2002, 690 patients who had successfully undergone a laparoscopic cholecystectomy were reviewed. According to the type of clip, we retrospectively identified two groups of patients: 199 in whom the surgeons had used absorbable clips (absorbable clip group, ACG) and 491 in whom the surgeons had used titanium nonabsorbable clips (titanium clip group, TCG). Data about demographics, operation, results, complications, and follow-up were collected and matched in the two groups. Demographics, concomitant surgery, and the American Society of Anesthesiologists (ASA) status were comparable between the two groups. Although the proportions of cases requiring urgent operation, intraoperative cholangiography, use of a fourth trocar, and use of drainage suction were similar, the difficulty score of the operation was lower (6.3 vs. 7.0, P =.03) and the operative time was shorter (44 vs. 61 minutes, P <.0001) in the ACG than in the TCG. Complications, hospital stay, and long-term results were satisfactory and comparable between the two groups. No correlation was found between clip type and the incidence of biliary tree injuries, bleeding, wound infection, or readmission. The cost of the two types of clips varied slightly (90 euros for each procedure). Despite the fact that absorbable clips are theoretically less likely to cause complications than metallic ones, we were not able to demonstrate any clinical advantage during laparoscopic cholecystectomy in this retrospective study. Furthermore, the results suggest that absorbable clips are preferred when the cholecystectomy presents fewer difficulties.

Laparoscopic treatment of ventral hernias: prospective evaluation.

We describe 50 patients who recently underwent laparoscopic surgery. Early results, complications, and follow-up data were collected prospectively. Of 50 patients, 34 had an incisional hernia, whereas 16 had a primary defect. Three trocars were inserted. EndoShears or Ultracision was used for tissue manipulation. The prosthetic mesh used was an expanded polytetrafluoroethylene (ePTFE) mesh, inserted through the first trocar and fixed with a helicoidal stapler. Patients were followed-up in the outpatient clinic (mean, 14 months). Every operation was successfully completed, and mean operative time was 103 minutes. There were two small bowel injuries (4%) repaired by minilaparotomy. Postoperative pain was limited. Bowel movements, ambulation, and discharge were prompt. We noted 4 cases of urinary retention (8%), 8 seromas (16%), and 1 prolonged ileus, which resolved on day 5 spontaneously. Mean postoperative stay was 4 days. One patient was readmitted after 4 weeks because of incomplete obstruction, resolved conservatively. There has been only 1 recurrence (2%), 8 months after the operation. The technique appears safe and efficacious.