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1.
Ann Surg ; 261(5): 902-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25361220

ABSTRACT

OBJECTIVE: The study objectives were to analyze the impact of the number of lymph nodes (LNs) reported as resected (NLNr) and the number of LNs invaded (NLNi) on the prognosis of esophageal cancer (EC) after neoadjuvant chemoradiotherapy. BACKGROUND: Pathological LN status is a major disease prognostic factor and marker of surgical quality. The impact of neoadjuvant chemoradiation (nCRT) on LN status remains poorly studied in EC. METHODS: Post hoc analysis from a phase III randomized controlled trial comparing nCRT and surgery (group nCRT) to surgery alone (group S) in stage I and II EC (NCT00047112). Only patients who underwent surgical resection were considered (n = 170). RESULTS: nCRT resulted in tumoral downstaging (pT0, 40.7% vs 1.1%, P < 0.001), LN downstaging (pN0, 69.1% vs 47.2%, P = 0.016), and reduction in the median NLNr [16.0 (range, 0-47.0) vs 22.0 (range, 3.0-58.0), P = 0.001] and NLNi [0 (range, 0-25) vs 1.0 (range, 0-25), P = 0.001]. A good histological response (TRG1/2) in the resected esophageal specimen correlated with reduced median NLNi [0 (range, 0-10) vs 1.0 (range, 0-4), P = 0.007]. After adjustment by treatment, NLNi [hazards ratio (HR) (1-3 vs 0) 3.5, 95% confidence interval (CI): 2.3-5.5, and HR (>3 vs 0) 3.5, 95% CI: 2.0-6.2, P < 0.001] correlated with prognosis, whereas NLNr [HR (<15 vs ≥15) 0.95, 95% CI: 0.6-1.4, P = 0.807 and HR (<23 vs ≥23) 1.4, 95% CI: 0.9-2.0, P = 0.131] did not. In Poisson regression analysis, nCRT was an independent predictive variable for reduced NLNr [exp(coefficient) 0.80, 95% CI: 0.66-0.96, P = 0.018]. CONCLUSIONS: nCRT is not only responsible for disease downstaging but also predicts fewer LNs being identified after surgical resection for EC. This has implications for the current quality criteria for surgical resection.


Subject(s)
Chemoradiotherapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Lymph Nodes/pathology , Neoadjuvant Therapy , Adult , Aged , Esophageal Neoplasms/surgery , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Survival Analysis
2.
Bull Acad Natl Med ; 197(2): 443-55; discussion 455-6, 2013 Feb.
Article in French | MEDLINE | ID: mdl-24919373

ABSTRACT

INTRODUCTION: The signet ring cell (SRC) histological subtype is a factor of poor prognosis in advanced gastric adenocarcinomas, but its prognostic value in early gastric cancer is unclear. The aim of this study was to evaluate the prognostic impact of SRC in superficial gastric adenocarcinomas, based on a comparison of patients with SRC and non SRC histologies. PATIENTS AND METHODS: From a large national cohort of 3,010 patients operated on for gastric adenocarcinoma between January 1997 and January 2010, we selected patients with pTis or pT1 tumors and compared those with SRC and non SRC histology on the basis of demographic, surgical and histologic factors and outcomes. The primary endpoint was the 3-year survival rate. RESULTS: Among 421 patients with a pTis or pT1 tumor, 104 (24.7%) had the SRC subtype and 317 (75.3%) a non SRC subtype. Median age was significantly lower in the SRC group than in the non SRC group (59.6 vs 68.8 years, p<0.001). Other demographic variables were similar in the two groups. Extensive surgical resection was more frequent in the non SRC group (31.9% vs 12.5%, p<0.001), but R0 resection rates were similar (97.5% vs 98.1%, p=0.900). The submucosa was more frequently involved in the SRC group (94.2% vs 84.9%, p=0.043), while lymph node involvement and the number of invaded nodes were similar in the two groups. Recurrences (5.8% vs 8.8%, p=0.223) and sites of recurrence (especially peritoneal carcinomatosis, 1.9% vs 1.6% ; p=0.838) were similar in the two groups. The 3-year survival rate was similar in the SRC and non SRC groups (94.1% vs 89.9%, p=0. 403), although the median survival time had not been reached CONCLUSION: SRC is not a prognostic factor in superficial gastric adenocarcinoma.


Subject(s)
Carcinoma, Signet Ring Cell/mortality , Carcinoma, Signet Ring Cell/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Aged , Carcinoma, Signet Ring Cell/surgery , Cohort Studies , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Prognosis , Retrospective Studies , Stomach Neoplasms/surgery
4.
World J Surg ; 36(2): 346-54, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22102091

ABSTRACT

BACKGROUND: Signet ring cell (SRC) carcinoma is defined as an adenocarcinoma in which >50% of the total operative specimen consists of isolated or small groups of malignant cells containing intracytoplasmic mucins (hSRCs). We previously demonstrated that hSRCs are a predictor of poor prognosis with specific tumoral characteristics suggesting the need for a dedicated therapeutic strategy before surgery. However diagnostic accuracy and prognostic value of SRCs on pretreatment biopsies (bSRCs) is unknown. The aim of the study was to determine if bSRCs can accurately predict hSRCs and survival. METHODS: A retrospective analysis was performed among 254 patients with an adenocarcinoma. We performed pretreatment endoscopic biopsies and histopathologic analysis of the surgical specimen. Pretreatment endoscopic biopsy results were compared with definitive pathologic results and were correlated with long-term survival. RESULTS: From 254 patients enrolled, 96 had bSRCs (37.8%), and 101 (39.8%) had hSRCs. Pretreatment biopsy results were correct in 89 of 101 patients with hSRC (sensitivity 88.1%) and in 146 of 153 with histologic non-SRCs (hNSRCs) (specificity 95.4%). The positive and negative predictive values for the biopsies were 92.7, and 92.4%, respectively, with an overall accuracy of 92.5%. When compared to the biopsy results, non-SRCs (bNSRCs), bSRCs were associated with poorer survival and were identified as an independent factor for poor prognosis (hazard ratio 1.89 with 95% confidence interval 1.35 to 2.64, P < 0.001). CONCLUSIONS: The presence of signet ring cells in samples obtained from routine pretreatment endoscopic biopsies accurately predicts SRC histology and poor prognosis. The specific therapeutic strategy can consequently be considered from the initial diagnosis.


Subject(s)
Biopsy , Carcinoma, Signet Ring Cell/pathology , Gastroscopy , Preoperative Care , Stomach Neoplasms/pathology , Aged , Carcinoma, Signet Ring Cell/mortality , Carcinoma, Signet Ring Cell/surgery , Female , Follow-Up Studies , Gastrectomy , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Retrospective Studies , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Survival Analysis , Survival Rate
5.
Lancet Oncol ; 12(3): 296-305, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21109491

ABSTRACT

Gastric and oesophageal cancers are among the leading causes of cancer-related death worldwide. By contrast with the decreasing prevalence of gastric cancer, incidence and prevalence of oesophagogastric junction adenocarcinoma (OGJA) are rising rapidly in developed countries. We provide an update about treatment strategies for resectable OGJA. Here we review findings from the latest randomised trials and meta-analyses, and propose guidelines regarding endoscopic, surgical, and perioperative treatments. Through a team approach, members from all diagnostic and therapeutic disciplines, such as gastroenterologists, surgeons, oncologists, radiologists, and radiotherapists, can effectively administer a range of treatment modalities.


Subject(s)
Adenocarcinoma/therapy , Esophageal Neoplasms/therapy , Stomach Neoplasms/therapy , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Antineoplastic Agents/therapeutic use , Combined Modality Therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophagogastric Junction/pathology , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
6.
BMC Cancer ; 11: 310, 2011 Jul 23.
Article in English | MEDLINE | ID: mdl-21781337

ABSTRACT

BACKGROUND: Open transthoracic oesophagectomy is the standard treatment for infracarinal resectable oesophageal carcinomas, although it is associated with high mortality and morbidity rates of 2 to 10% and 30 to 50%, respectively, for both the abdominal and thoracic approaches. The worldwide popularity of laparoscopic techniques is based on promising results, including lower postoperative morbidity rates, which are related to the reduced postoperative trauma. We hypothesise that the laparoscopic abdominal approach (laparoscopic gastric mobilisation) in oesophageal cancer surgery will decrease the major postoperative complication rate due to the reduced surgical trauma. METHODS/DESIGN: The MIRO trial is an open, controlled, prospective, randomised multicentre phase III trial. Patients in study arm A will receive laparoscopic-assisted oesophagectomy, i.e., a transthoracic oesophagectomy with two-field lymphadenectomy and laparoscopic gastric mobilisation. Patients in study arm B will receive the same procedure, but with the conventional open abdominal approach. The primary objective of the study is to evaluate the major postoperative 30-day morbidity. Secondary objectives are to assess the overall 30-day morbidity, 30-day mortality, 30-day pulmonary morbidity, disease-free survival, overall survival as well as quality of life and to perform medico-economic analysis. A total of 200 patients will be enrolled, and two safety analyses will be performed using 25 and 50 patients included in arm A. DISCUSSION: Postoperative morbidity remains high after oesophageal cancer surgery, especially due to major pulmonary complications, which are responsible for 50% of the postoperative deaths. This study represents the first randomised controlled phase III trial to evaluate the benefits of the minimally invasive approach with respect to the postoperative course and oncological outcomes in oesophageal cancer surgery. TRIAL REGISTRATION: NCT00937456 (ClinicalTrials.gov).


Subject(s)
Adenocarcinoma/surgery , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/surgery , Esophagectomy/methods , Laparoscopy , Adult , Aged , Esophagus/pathology , Esophagus/surgery , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lymph Node Excision , Middle Aged , Postoperative Care , Preoperative Care , Prospective Studies , Stomach/surgery , Thoracotomy , Young Adult
7.
Bull Acad Natl Med ; 195(1): 93-112, 2011 Jan.
Article in French | MEDLINE | ID: mdl-22039706

ABSTRACT

Management of esophageal cancer has evolvedmarkedly in the last two decades. Advances in neoadjuvant treatment combined with refinements in surgical techniques and perioperative care have resulted in better postoperative outcomes and long-term survival. We investigated trends in the outcome of esophagectomy for esophageal cancer over the past 20 years at our high-volume institution. We studied patients who underwent surgery for primary cancer of the esophagus or gastroesophageal junction from 1988 through 2008 (N = 1153). Four study periods (P) were compared: 1988-1993 (P1), 1994-1998 (P2), 1999-2003 (P3) and 2004-2008 (P4). Demographic parameters, tumor characteristics, post-operative morbidity, in-hospital mortality and long-term survival were recorded prospectively and the four periods were compared retrospectively. Squamous cell carcinoma accountedfor 77.4% of the 1153 malignancies. The ratio of squamous cell carcinoma to adenocarcinoma fell from 12.0 to 1.3 during the study period (P1 vs P4, P < 0.001), with aparallel increase in the number tumors of the lower esophagus or gastroesophageal junction. The post-operative mortality and morbidity rates were respectively 5.6% and 42.7% overall and remained stable during the study period. The five-year survival rate among all resected patients improved significantly, from 24.3% to 42.7% (P1 vs P4, P< 0.001). The complete (RO) resection rate was 80.7% overall and increased from 74.1% to 82.1% (P1 vs P4, P < 0.05). The five-year survival rate improved significantly among RO-resected patients, from 32.7 % to 52.3 % (PI vs P4, P<.0001). The proportion of patients who received neoadjuvant treatment (mainly chemoradiotherapy) rose from 46.8% to 66.5%. The completeness of the pathologic response after neoadjuvant chemoradiotherapy correlated with long-term survival (P < 0.001): five-year survival rates among pathologically complete, partial and non responders were 52.1%, 24.8% and 10%, respectively. Short-term outcomes after resection remained stable during the study period and comparedfavorably with those reported by other high-volume institutions. Long-term survival improved significantly. Advances in staging methods andsurgical management, combined with more stringent patient selection and use of neoadjuvant chemoradiation, may explain this progress. More reliable predictors of complete RO resection and of the response to chemoradiation therapy are needed in order to tailor management to the individual patient.


Subject(s)
Esophageal Neoplasms/surgery , Esophagogastric Junction/surgery , Carcinoma/mortality , Carcinoma/surgery , Esophageal Neoplasms/mortality , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy/statistics & numerical data , Neoadjuvant Therapy/trends , Retrospective Studies
8.
Chemotherapy ; 56(3): 234-8, 2010.
Article in English | MEDLINE | ID: mdl-20551640

ABSTRACT

BACKGROUNDS: The combination gemcitabine-oxaliplatin (GEMOX) is frequently used in patients with advanced biliary tract carcinoma (BTC). However, this is only based on phase II studies performed in selected patients.We assessed the efficacy and safety of the GEMOX regimen in non-selected patients with advanced BTC. METHODS: All consecutive patients with advanced BTC received the GEMOX regimen in a setting outside a study: gemcitabine 1,000 mg/m(2) on day 1, and oxaliplatin 100 mg/m(2) on day 2, treatment repeated every 2 weeks until progression or unacceptable toxicity. RESULTS: Forty-four patients were enrolled. EFFICACY: 1 complete and 6 partial responses (objective response rate = 16.3%), 18 tumour stabilizations (41.9%, disease control rate = 58.1%), median progression-free survival was 5.0 months and median overall survival was 11.0 months. TOXICITY: grade 3 neuropathy in 4 patients, grade 3 asthenia in 5 patients. CONCLUSION: The GEMOX combination was well tolerated, with a modest activity in non-selected patients with advanced BTC. This regimen should be compared to the new standard gemcitabine-cisplatin combination.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biliary Tract Neoplasms/drug therapy , Carcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Biliary Tract Neoplasms/mortality , Biliary Tract Neoplasms/pathology , Carcinoma/mortality , Carcinoma/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Treatment Outcome
10.
Presse Med ; 36(3 Pt 2): 496-500, 2007 Mar.
Article in French | MEDLINE | ID: mdl-17336859

ABSTRACT

The prognosis for esophageal cancer remains grim despite recent progress in diagnosis and treatment. Surgery is the standard treatment for stages I and II (only). Neoadjuvant chemotherapy or combined radiation and chemotherapy may be considered for stages IIb and III. Palliative surgery is no longer considered useful. Neoadjuvant or adjuvant radiation treatment does not improve survival. Adjuvant chemotherapy does not improve survival, and the benefits of its neoadjuvant use remain controversial in view of the discordant results. There is strong evidence that a neoadjuvant combination of radiation and chemotherapy improves resection and survival rates compared with surgery alone, but definitive proof is not currently available. Combined radiation and chemotherapy may be considered for locally advanced tumors in responding patients, with curative salvage surgery if the tumor persists. For patients whose tumor is inoperable, a combination of radiation and chemotherapy is the standard treatment.


Subject(s)
Esophageal Neoplasms/therapy , Esophageal Neoplasms/pathology , Humans , Neoplasm Metastasis , Neoplasm Staging
11.
Hum Mutat ; 27(10): 1064, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16941501

ABSTRACT

Familial adenomatous polyposis has been linked to germline mutations in the APC tumor suppressor gene. However, a number of patients with familial adenomatous polyposis (with either classical or attenuated phenotype) have no APC mutation. Recently, germline mutations in the Wnt pathway component gene AXIN2 have been associated with tooth agenesis-colorectal cancer syndrome. Moreover, biallelic mutations in the base excision repair gene MUTYH have been associated with polyposis and early-onset colorectal cancer. The aim of this study was to further assess the contribution of AXIN2 and MUTYH to hereditary colorectal cancer susceptibility. AXIN2 and MUTYH genes were screened for germline mutations by PCR and direct sequencing in 39 unrelated patients with multiple adenomas or colorectal cancer without evidence of APC mutation nor mismatch repair defect. Two novel AXIN2 variants were detected in one patient with multiple adenomas, but no clearly pathogenic mutation. In contrast, nine different MUTYH mutations were detected in eight patients, including four novel mutations. Biallelic MUTYH mutations were only found in patients with multiple adenomatous polyposis (7 out of 22 (32%)). Interestingly, five MUTYH mutation carriers had a family history consistent with dominant inheritance. Moreover, one patient with biallelic MUTYH mutations presented with multiple adenomas and severe tooth agenesis. Therefore, germline mutations are rare in AXIN2 but frequent in MUTYH in patients with multiple adenomas. Our data suggest that genetic testing of MUTYH may be of interest in patients with pedigrees apparently compatible with autosomal recessive as well as dominant inheritance.


Subject(s)
Adenomatous Polyposis Coli/genetics , Cytoskeletal Proteins/genetics , DNA Glycosylases/genetics , Mutation/genetics , Adenomatous Polyposis Coli/pathology , Adolescent , Adult , Aged , Axin Protein , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Mutational Analysis/methods , Female , Gene Frequency , Genetic Predisposition to Disease/genetics , Germ-Line Mutation/genetics , Humans , Male , Middle Aged , Models, Genetic , Pedigree
12.
Gastroenterol Clin Biol ; 30(8-9): 1085-9, 2006.
Article in French | MEDLINE | ID: mdl-17075456

ABSTRACT

Congenital duodenal atresia is usually associated with various congenital anomalies. The embryological events in the development of the biliary tract and duodenum are linked. Although an association between duodenal atresia and biliary anomalies is predictable, it is rarely observed. We describe the case of a 27 year-old woman, operated on for duodenal atresia in her childhood, who presented cholangiolitis. Morphologic investigation allowed the diagnosis of choledochal cyst with an intracystic stone developed in the pancreatic head. A pancreatico-duodenectomy was performed because of the importance and the location of dilatation and stone with biliary obstruction. To our knowledge, the association between a congenital duodenal atresia and a choledochal cyst revealed at adult age had never been described in the literature.


Subject(s)
Choledochal Cyst/complications , Duodenal Obstruction/congenital , Intestinal Atresia/complications , Adult , Choledochal Cyst/surgery , Cholelithiasis/diagnosis , Cholelithiasis/surgery , Cholestasis/etiology , Cholestasis/surgery , Duodenal Obstruction/surgery , Female , Humans , Intestinal Atresia/surgery , Pancreaticoduodenectomy
13.
Prog Urol ; 16(5): 588-93, 2006 Nov.
Article in French | MEDLINE | ID: mdl-17175957

ABSTRACT

OBJECTIVES: To evaluate the clinical features, staging by medical imaging, treatment strategy and results of surgical management of deep pelvic endometriosis with bladder and/or ureteric involvement. MATERIALS AND METHODS: Eighteen cases of ureteric and/or bladder deep pelvic endometriosis (DPE) were treated in our centre between 1996 and 2004. Preoperative data (clinical symptoms, MR imaging), intraoperative data (resection and urinary tract diversion procedures, associated procedures on the genital and gastrointestinal tracts), and postoperative data (histological results, complications, anatomical follow-up by imaging and functional assessment) were reviewed. RESULTS: Urinary symptoms were present in 55% of cases, genital symptoms were present in 83% of cases and gastrointestinal symptoms were present in 46% of cases. A combination of gynaecological and gastrointestinal lesions was demonstrated on imaging in 82% of cases. The mean postoperative follow-up was 16 months (range: 6-36 months). Six patients presented anterior vesical endometriosis. In these cases, the sensitivity and specificity of MRI were 100%. Six partial cystectomies were performed. All corresponded to endometriotic lesions on histological examination. No cases of recurrence of vesical endometriosis were observed. Posterior endometriosis with ureteric involvement was observed in 13 patients (including one with vesical endometriosis). The ureteric lesion was asymptomatic in 8 out of 13 cases (61%). The diagnostic sensitivity of MRI was 92% for posterior nodules, identifying 4 lateral parametrial nodules and 8 median retrocervical nodules. Ureterohydronephrosis was observed in 3 patients with lateral parametrial nodules and 8 patients with median retrocervical nodules, and was bilateral for 3 patients, i.e. 14 dilated renal units. Surgical management consisted of 2 ureteric resections with end-to-end anastomosis, 3 psoas bladder reimplantations, and 9 ureterolyses (8 patients). Two out of 13 patients (15%) with ureteric lesions treated by ureterolysis developed recurrence of the ureteric stricture with upper tract dilatation related to recurrence of the lateral nodule. In 14 patients, genital and/or gastrointestinal resections were associated with the urinary tract procedure. CONCLUSION: Preoperative evaluation of all DPE lesions is based on MRI with reconstruction images of the ureter in the presence of urinary tract lesions. Systematic ureteric stenting prior to surgical dissection of the pelvic wall is recommended in patients with posterior nodules and in the case of partial cystectomy for anterior nodules when the ureteric meati are adjacent to the lesion. Ureteric reimplantation onto a psoas hitch bladder must be performed when the DPE lesions are extensive and partly resected or invade the ureteric wall. The frequency of associated lesions (urinary, gynaecological gastrointestinal) justifies a multidisciplinary surgical approach.


Subject(s)
Endometriosis/surgery , Ureteral Diseases/surgery , Urinary Bladder Diseases/surgery , Adult , Endometriosis/diagnosis , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Retrospective Studies , Ureteral Diseases/diagnosis , Urinary Bladder Diseases/diagnosis , Urologic Surgical Procedures
14.
J Am Coll Surg ; 201(2): 253-62, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16038824

ABSTRACT

BACKGROUND: Resection for adenocarcinoma of the gastroesophageal junction (AGEJ) is associated with severe mortality and morbidity. This retrospective study aimed to evaluate mortality and morbidity after resection for AGEJ and to determine their predictive factors. STUDY DESIGN: Data from 1,192 patients (mean age 65 +/- 11 years) who underwent resection for AGEJ by members of French Association of Surgery from 1985 to 2000 were collected. A stepwise logistic regression model was built to identify by multivariate analysis the variables independently associated with mortality, morbidity, anastomotic leakage, and major pulmonary complications. RESULTS: Distribution of Siewert's type was: I = 480 (40%), II = 500 (42%), and III = 212 (18%). Most type I and II tumors were treated by esophagectomy and proximal gastrectomy (93% and 58%, respectively), using an approach including a thoracotomy (82% and 64%, respectively); type III tumors were treated mainly by total gastrectomy and distal esophagectomy (83%), through an exclusive transabdominal approach (69%). Seventy-six (6%) patients died postoperatively. Only American Society of Anesthesiologists (ASA) scores III and IV (p < 0.001) and period of study (p = 0.025) were predictive of mortality. Predictive factors of overall morbidity (overall rate = 35%) were high ASA score (p < 0.001), age more than 60 years (p = 0.020), male gender (p = 0.039), and cervical anastomosis (p = 0.001). Factors predictive of anastomotic leakage (overall rate = 9%) were high ASA score (p = 0.006) and manual anastomosis (p = 0.010). Factors predictive of major pulmonary complications (overall rate = 23%) were high ASA score (p = 0.015), age more than 60 years (p < 0.001), anastomotic leakage (p < 0.001), and abdominal complications (p = 0.003). CONCLUSIONS: ASA score is a reliable predictive factor of operative mortality and morbidity after resection of AGEJ.


Subject(s)
Adenocarcinoma/surgery , Esophageal Neoplasms/surgery , Esophagectomy , Esophagogastric Junction , Gastrectomy , Stomach Neoplasms/surgery , Actuarial Analysis , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophagectomy/adverse effects , Esophagectomy/methods , Esophagectomy/mortality , Female , France/epidemiology , Gastrectomy/adverse effects , Gastrectomy/methods , Gastrectomy/mortality , Hospital Mortality , Humans , Logistic Models , Male , Middle Aged , Morbidity , Multivariate Analysis , Neoadjuvant Therapy , Neoplasm Staging , Retrospective Studies , Risk Factors , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Surveys and Questionnaires , Survival Analysis
15.
Biochem J ; 377(Pt 3): 701-8, 2004 Feb 01.
Article in English | MEDLINE | ID: mdl-14583090

ABSTRACT

Abnormal gastro-oesophageal reflux and bile acids have been linked to the presence of Barrett's oesophageal premalignant lesion associated with an increase in mucin-producing goblet cells and MUC4 mucin gene overexpression. However, the molecular mechanisms underlying the regulation of MUC4 by bile acids are unknown. Since total bile is a complex mixture, we undertook to identify which bile acids are responsible for MUC4 up-regulation by using a wide panel of bile acids and their conjugates. MUC4 apomucin expression was studied by immunohistochemistry both in patient biopsies and OE33 oesophageal cancer cell line. MUC4 mRNA levels and promoter regulation were studied by reverse transcriptase-PCR and transient transfection assays respectively. We show that among the bile acids tested, taurocholic, taurodeoxycholic, taurochenodeoxycholic and glycocholic acids and sodium glycocholate are strong activators of MUC4 expression and that this regulation occurs at the transcriptional level. By using specific pharmacological inhibitors of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, protein kinase A and protein kinase C, we demonstrate that bile acid-mediated up-regulation of MUC4 is promoter-specific and mainly involves activation of phosphatidylinositol 3-kinase. This new mechanism of regulation of MUC4 mucin gene points out an important role for bile acids as key molecules in targeting MUC4 overexpression in early stages of oesophageal carcinogenesis.


Subject(s)
Adenocarcinoma/genetics , Bile Acids and Salts/physiology , Esophageal Neoplasms/genetics , Mucins/genetics , Phosphatidylinositol 3-Kinases/metabolism , Promoter Regions, Genetic/physiology , Signal Transduction/physiology , Stomach Neoplasms/genetics , Transcription, Genetic/physiology , Adenocarcinoma/enzymology , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Bile Acids and Salts/pharmacology , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Cell Line, Tumor , Enzyme Activation/physiology , Esophageal Neoplasms/enzymology , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Gastric Mucins/genetics , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , Humans , Mucin-1/biosynthesis , Mucin-4 , Mucins/biosynthesis , Mucous Membrane/chemistry , Mucous Membrane/metabolism , Peptide Fragments/biosynthesis , Promoter Regions, Genetic/drug effects , Promoter Regions, Genetic/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/metabolism , Signal Transduction/drug effects , Stomach Neoplasms/enzymology , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Transcription, Genetic/drug effects , Up-Regulation/drug effects , Up-Regulation/physiology
16.
Ann Thorac Surg ; 75(6): 1720-6, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12822606

ABSTRACT

BACKGROUND: Esophagectomy remains a standard treatment for patients with resectable esophageal cancer, but the 5-year survival is only 20% to 25%. After complete resection survival is significantly longer than after incomplete resection with microscopic or macroscopic penetration. The purpose of this study was to prospectively identify the factors predictive of complete resection of operable esophageal cancers. METHODS: Betwen January 1995 and January 2002, 372 patients with esophageal cancer underwent surgery with curative intent. Complete resection was performed in 304 patients (81.7%), incomplete resection with microscopic penetration in 28 (7.5%), and incomplete resection with macroscopic penetration in 40 (10.8%). Univariate and multivariate analysis included 16 preoperative and operative factors. RESULTS: Factors predictive of complete resection were absence of any modification of the esophageal axis on the barium swallow (p = 0.019) and a partial or complete response to preoperative radiochemotherapy (p = 0.042). Three groups of patients were identified: group 1 had no deviation of the axis on the barium swallow (n = 253); group 2 had deviation of the axis on the barium swallow and partial or complete response to radiochemotherapy (n = 66); and group 3 had deviation of the axis on the barium swallow and no response to radiochemotherapy or no preoperative treatment (n = 53). Rates of complete resection were 90.1%, 74.2%, and 50.9%, and 5-year actuarial survivals were 46%, 37%, and 0%, respectively (p < 0.001). CONCLUSIONS: Complete resection of esophageal cancer is predictable. Deviation axis on the barium swallow and morphologic response to neoadjuvant radiochemotherapy are variables available for all patients at onset of therapeutic management.


Subject(s)
Adenocarcinoma/surgery , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/surgery , Esophagectomy , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Barium Sulfate , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Combined Modality Therapy , Contrast Media , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophagoscopy , Esophagus/diagnostic imaging , Esophagus/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multivariate Analysis , Neoadjuvant Therapy/methods , Neoadjuvant Therapy/mortality , Neoplasm Invasiveness , Predictive Value of Tests , Prospective Studies , Radiography , Survival Rate
17.
Gastroenterol Clin Biol ; 26(5): 454-62, 2002 May.
Article in French | MEDLINE | ID: mdl-12122354

ABSTRACT

OBJECTIVE: Surgery is the treatment of reference for early-stage esophageal cancer, but 5-year survival is only 20% to 25%. After complete resection (R0), survival is significantly longer than after incomplete resection, with microscopic (R1) or macroscopic (R2) penetration. The purpose of this work was to identify retrospectively the factors predictive of complete resection of operable esophageal cancers. PATIENTS AND METHODS: Between January 1982 and March 2001, 746 patients with esophageal cancer underwent curative surgery. R0 resection was performed in 585 patients (78.4%), R1 in 61 (8.2%) and R2 in 100 (13.4%). Univariate and multivariate analysis included 28 preoperative, clinical, tumor and therapeutic parameters. RESULTS: Multivariate analysis showed that factors predictive of complete resection R0 were: absence of any modification of the esophageal axis on the barium swallow (P=0.054), a partial or complete response to preoperative radio-chemotherapy (P=0.042), tumor height<10 cm (P=0.1) and tumor diameter<30 mm (P=0.01). Three groups of patients were identified from the 2 most significant variables. Group 1: no deviation of the axis on the barium swallow (n=501). Group 2: deviation of the axis on the barium swallow and partial or complete response to radiochemotherapy (n=91). Group 3: deviation of the axis on the barium swallow and no response to radiochemotherapy or no preoperative treatment (n=126). For the three groups, rate of R0 resection was 82.6%, 80.1% and 61.1% and 5-year actuarial survival 36%, 27% and 14%, respectively. These rates were significantly different between groups (P<10(- 4)) and two by two (P<0.04). CONCLUSION: Complete resection of esophageal cancer is predictable. After validation with an independent population the findings presented here could be used to establish stratification criteria for future therapeutic trials.


Subject(s)
Esophageal Neoplasms/surgery , Analysis of Variance , Antineoplastic Agents/administration & dosage , Esophageal Neoplasms/mortality , Esophageal Neoplasms/therapy , Female , Humans , Male , Middle Aged , Preoperative Care , Radiotherapy , Survival Rate
18.
Gastroenterol Clin Biol ; 26(8-9): 782-5, 2002.
Article in French | MEDLINE | ID: mdl-12434081

ABSTRACT

We report two cases of fundic endocrine tumors associated with fundic atrophic gastritis-related hypergastrinemia and treated by antrectomy. About twenty infracentimetric tumors were observed in each patient and restrictively involved fundic mucosa. Antrectomy induced normalization of gastrinemia and the disappearance of fundic tumors, as soon as the 4(th) and 7(th) month. No recurrence was observed during the 5-year and 18-month follow-up time, respectively. We therefore consider that antrectomy may be regarded as a useful alternative treatment in the management of atrophic gastritis-related fundic endocrine tumors.


Subject(s)
Carcinoid Tumor/etiology , Carcinoid Tumor/surgery , Gastrectomy/methods , Gastric Fundus/surgery , Gastritis, Atrophic/complications , Pyloric Antrum/surgery , Stomach Neoplasms/etiology , Stomach Neoplasms/surgery , Abdominal Pain/etiology , Adult , Biopsy , Carcinoid Tumor/classification , Carcinoid Tumor/diagnosis , Dyspepsia/etiology , Enterochromaffin-like Cells , Female , Follow-Up Studies , Gastrins/blood , Gastritis, Atrophic/pathology , Gastroscopy , Humans , Immunohistochemistry , Middle Aged , Stomach Neoplasms/blood , Stomach Neoplasms/diagnosis , Treatment Outcome
19.
Presse Med ; 43(3): 301-4, 2014 Mar.
Article in French | MEDLINE | ID: mdl-24530140

ABSTRACT

Development of outpatient cases in emergency is still a controversy. Ambulatory surgery is possible in ambulatory surgical unit (ASU), or in emergency surgical units (ESU). Quality of care and safety need to be associated to patients' ambulatory management without impairment of ASU and ESU organization. Patient eligibility concerns not only traumatic hand surgery but also general or visceral surgery.


Subject(s)
Ambulatory Surgical Procedures/methods , Emergency Treatment , Humans , Quality of Health Care
20.
J Clin Oncol ; 32(23): 2416-22, 2014 Aug 10.
Article in English | MEDLINE | ID: mdl-24982463

ABSTRACT

PURPOSE: Although often investigated in locally advanced esophageal cancer (EC), the impact of neoadjuvant chemoradiotherapy (NCRT) in early stages is unknown. The aim of this multicenter randomized phase III trial was to assess whether NCRT improves outcomes for patients with stage I or II EC. METHODS: The primary end point was overall survival. Secondary end points were disease-free survival, postoperative morbidity, in-hospital mortality, R0 resection rate, and prognostic factor identification. From June 2000 to June 2009, 195 patients in 30 centers were randomly assigned to surgery alone (group S; n = 97) or NCRT followed by surgery (group CRT; n = 98). CRT protocol was 45 Gy in 25 fractions over 5 weeks with two courses of concomitant chemotherapy composed of fluorouracil 800 mg/m(2) and cisplatin 75 mg/m(2). We report the long-term results of the final analysis, after a median follow-up of 93.6 months. RESULTS: Pretreatment disease was stage I in 19.0%, IIA in 53.3%, and IIB in 27.7% of patients. For group CRT compared with group S, R0 resection rate was 93.8% versus 92.1% (P = .749), with 3-year overall survival rate of 47.5% versus 53.0% (hazard ratio [HR], 0.99; 95% CI, 0.69 to 1.40; P = .94) and postoperative mortality rate of 11.1% versus 3.4% (P = .049), respectively. Because interim analysis of the primary end point revealed an improbability of demonstrating the superiority of either treatment arm (HR, 1.09; 95% CI, 0.75 to 1.59; P = .66), the trial was stopped for anticipated futility. CONCLUSION: Compared with surgery alone, NCRT with cisplatin plus fluorouracil does not improve R0 resection rate or survival but enhances postoperative mortality in patients with stage I or II EC.


Subject(s)
Esophageal Neoplasms/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy, Adjuvant , Cisplatin/administration & dosage , Disease-Free Survival , Esophageal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoplasm Staging , Radiotherapy, Conformal
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