Impact of neoadjuvant chemoradiation on lymph node status in esophageal cancer: post hoc analysis of a randomized controlled trial.

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.

Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of randomized controlled phase III trial FFCD 9901.

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.

[Ambulatory emergency surgery]. / Quelle place pour les urgences en chirurgie ambulatoire ?

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.

Pancreatic metastases of renal clear cell carcinoma: a clinicopathological study of 11 cases with special emphasis on the usefulness of PAX2 and mesothelin for the distinction from primary ductal adenocarcinoma of the pancreas.

OBJECTIVE: To determine whether PAX2 and mesothelin immunohistochemistry add additional diagnostic value in discriminating between pancreatic metastasis of renal clear cell carcinoma (PMRCC) and primary ductal adenocarcinoma of the pancreas (PDAC). STUDY DESIGN: We retrospectively collected tissue from PMRCC and PDAC. Eleven cases of PMRCC registered at Lille University Hospitals from 2001 to 2010 were included. Eleven cases of PDAC were randomly selected from our files. A comparative immunohistochemical study with anti-PAX2, anti-mesothelin, and the classical renal antibodies anti-CD10 and anti-vimentin was performed on PMRCC and PDAC. RESULTS: We found that PMRCC displays a clinical presentation that might mimic primary pancreatic tumor, as PMRCC presented as a solitary mass in 8 cases and appeared a long time after diagnosis of a renal tumor (12.8 years, mean for metachronous metastasis). By immunohistochemistry we observed that PAX2, mesothelin, CD10 and vimentin stainings were noted in 10/11 (91%), 0/11 (0%), 11/11 (100%) and 7/11 cases (64%), respectively, among 11 PMRCC cases. All PDACs displayed diffuse mesothelin (100%) expression without PAX2 and vimentin (0%) staining, whereas CD10 was noted in 4/11 cases (36%). CONCLUSION: These data suggest that in difficult diagnostic cases both PAX2 and mesothelin immunohistochemical study may be useful in discriminating between PMRCC and primary pancreatic carcinoma.

[Does early signet ring cell gastric carcinoma carry a worse prognosis?]. / Tumeurs adénocarcinomateuses superficielles de l'estomac: un contingent majoritaire à cellules indépendantes est-il associé à un mauvais pronostic?

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.

Is pretreatment endoscopic biopsy a good predictor of signet ring cell histology in gastric carcinoma?

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.

[Cancer of the esophagus and gastroesophageal junction: evolution of surgical management]. / Cancer de l'oesophage et de la jonction oeso-gastrique: evolution de la stratégie chirurgicale.

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.

Open versus laparoscopically-assisted oesophagectomy for cancer: a multicentre randomised controlled phase III trial - the MIRO trial.

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).

[Salvage surgery: cancer of the esophagus]. / La chirurgie de rattrapage : le cancer de l'oesophage.

Neoadjuvant chemoradiotherapy is the gold standard of the treatment of advanced oesophageal cancer. The role of surgery after chemoradiotherapy is still debated. Feasibility of curative resection depends on dose of radiotherapy, morbimortality rates, and nutrition status at the end of the protocol especially for non-responders patients. Adding surgery to radiochemotherapy improves local tumour control but does not increase overall survival of patients with advanced oesophageal cancer. According to the two randomised trials published on the subject, surgery is not recommended after chemoradiotherapy for responders. Recommendations of French National Thesaurus are: exclusive chemoradiotherapy as reference, esophagectomy for residual tumour as alternative for operable patients. Surgery may be proposed for selected non-responders patients and some complete pathological response in expert center.

Oesophagogastric junction adenocarcinoma: which therapeutic approach?

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.

Experience of gemcitabine plus oxaliplatin chemotherapy in patients with advanced biliary tract carcinoma.

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.

Integration of neoadjuvant and adjuvant chemotherapy in patients with resectable liver metastases from colorectal cancer.

The liver is the primary metastatic site in patients with colorectal cancer, and the only hope for a cure or prolonged survival in patients with liver metastases is provided by surgical resection. Advances obtained in non-resectable metastatic disease using new chemotherapeutic agents raise important questions about the use of neoadjuvant and adjuvant chemotherapy in patients with resectable liver metastases. Two major randomized studies have yielded positive results. First, a combined intra-arterial plus systemic fluoropyrimidine-based chemotherapy regimen demonstrated a relapse-free survival benefit when compared to systemic 5-fluorouracil-leucovorin therapy alone. This approach is still restricted to specialized centres, however, due to technical limitations and locoregional toxicities. Secondly, an EORTC trial demonstrated the superiority of peri-operative FOLFOX-4 chemotherapy in comparison to surgery alone. Oxaliplatin and irinotecan can induce substantial liver damage, especially steatohepatitis and vascular lesions, but the impact of these lesions on postoperative morbidity and survival remains unclear. Ongoing and planned trials will assess the addition of anti-angiogenic and anti-epidermal growth factor receptor agents to chemotherapy regimens.

E-selectin gene S128R polymorphism is associated with poor prognosis in patients with stage II or III colorectal cancer.

Some host-related factors may predict the risk of metastasis after surgery of colorectal cancer (CRC). The endothelial adhesion molecule E-selectin is implicated in the metastatic spread of CRC. We postulated that some polymorphisms within the E-selectin gene, especially the S128R polymorphism, may increase the risk of metastases by facilitating adhesion of tumour cells to the endothelium. We collected blood samples for DNA extraction from 264 patients treated for stage II or III CRC and from 310 healthy controls in order to assess three polymorphisms within the E-selectin gene (S128R, G98T and L554F) and one within the P-selectin gene (V640L). Genotypes were analysed by the allelic discrimination TaqMan real-time PCR assay. The S128R polymorphism was detected in 59 patients (22.3%) and was strictly correlated with the G98T polymorphism. In multivariate analysis, the S128R polymorphism was associated with shorter event-free survival (EFS) and overall survival (OS) in the whole population (EFS: P=.003, HR 1.82, 95% CI 1.23-2.70; OS: P<10(-4), HR 4.31, 95% CI 2.46-10.99), in patients with stage II CRC(EFS: P=.04, HR 1.92, 95% CI 1.02-3.60; OS: P=.02, HR 4.44, 95% CI 1.16-17.03), and in patients with stage III CRC (EFS: P=.04, HR 1.68, 95% CI 1.01-2.80; OS: P=.001, HR 4.04, 95% CI 1.73-9.46). L554F and V640L polymorphisms had no prognostic value. The S128R polymorphism is a constitutional factor associated with a higher risk of relapse and death in patients treated for CRC. This polymorphism detection may permit better selection of patients suitable for adjuvant therapy, especially among those with stage II disease.

Life-threatening postoperative pancreatic fistula (grade C) after pancreaticoduodenectomy: incidence, prognosis, and risk factors.

BACKGROUND: Pancreatic fistula (PF) is one of the most common postoperative complications of pancreatoduodenectomy (PD). A recent International Study Group on Pancreatic Fistula (ISGPF) definition grades the severity of PF according to the clinical impact on the patient's hospital course. Although PF is generally treated conservatively (grade A), some cases may require interventional procedures (grade B) or may be life-threatening and necessitate emergency reoperation (grade C). The aim of the present study was to evaluate the incidence of postoperative grade C PF after PD and to assess the prognosis and risk factors for this life-threatening condition. STUDY DESIGN: Between January 2000 and December 2006, 680 consecutive patients underwent PD in 5 digestive surgery departments in the northwest region of France (Lille, Amiens, Rouen, and Caen). PF was defined as drain output of any measurable volume of fluid on or after postoperative day 3 with amylase content greater than 3 times the serum amylase activity (ISGPF guidelines). To identify possible risk factors for grade C PF, we reviewed the records of 111 (16.3%) patients with postoperative PF and compared grade C cases with grade A+B cases. RESULTS: The median age was 59 years (range 22-87). The male-to-female ratio was 1.6:1. Fifty-six (50.4%) PDs were performed via pancreaticogastrostomy and 55 via pancreaticojejunostomy. Overall mortality was 2% (n = 14). Grade C PF was observed in 36 (32%) patients, of whom 17 (47%) had sepsis due to an abdominal collection, 16 (44%) had postoperative bleeding, 10 (27.7%) had bleeding associated with abdominal collection, and 3 (9%) had multi-organ failure due to other causes. Of these 36 patients, 35 (97%) underwent reoperation. The mortality rate in grade C PF patients was 38.8%. The major causes of death were sepsis (n = 6) and recurrent bleeding after reoperation (n = 5). Grade C PF increased the duration of postoperative hospitalization (46 vs 29 days, P < .001). Univariate analysis showed that peroperative soft pancreatic parenchyma, peroperative blood transfusion, and postoperative bleeding were significant risk factors for grade C PF, with P values of .011, .003, and .001, respectively. No risk factors for grade C PF were identified in a multivariate analysis. The sensibility, specificity, positive predictive value, and negative predictive value of the presence of the 3 risk factors for grade C PF were 13.89%, 100%, 100%, and 70.75%, respectively. CONCLUSION: Sixteen percent of patients had PF after PD. Among them, 30% had grade C PF, with a mortality rate of about 40%. Achievement of a 100% predictive positive value for grade C PF after PD in individuals with 3 discriminant risk factors (peroperative soft pancreatic parenchyma, peroperative transfusion, and postoperative bleeding) is a first step towards the identification of high-risk patients who should be managed differently from other patients with PF during or after PD.

[Oesophageal cancer: what's new during the last 10 years?]. / Cancer de l'oesophage: quoi de neuf dans la prise en charge depuis 10 ans?

During the last 10 years, the incidence of lower third oesophagus and esogastric junction adenocarcinomas in western countries continued to increase whereas that of squamous cell carcinomas declined. In France, this trend was also observed even if it remained much fainter than that observed in the United States. Increasingly arguments incite to propose specific diagnostic and therapeutic approaches for each histological type. Preoperative work-up includes for some patients primary laparoscopic approach and positrons emission tomography. Indications for both procedures are specified in the recent recommendations of the National Thesaurus. Endoscopic approach is now a valuable option offered for selected patients treated in a curative or palliative attempt or sustaining postoperative fistula. Curative therapeutic strategies include surgery, chemotherapy, and radiotherapy, mostly in a combined fashion. Therapeutic strategies have markedly changed for 10 years, and their respective place is specified for each histological types and according to tumour location.

The number of metastatic lymph nodes and the ratio between metastatic and examined lymph nodes are independent prognostic factors in esophageal cancer regardless of neoadjuvant chemoradiation or lymphadenectomy extent.

OBJECTIVE: To investigate whether the number of lymph nodes metastasis (LNMs) and the ratio between metastatic and examined lymph nodes (LNs) are better prognostic factors when compared with traditional staging systems in patients with esophageal carcinoma. SUMMARY BACKGROUND DATA: The accuracy of the 6th UICC/TNM classification is suboptimal, especially when not taking into account neoadjuvant therapy and lymphadenectomy extent. METHODS: For 536 patients who underwent curative en bloc esophagectomy, in whom 51.5% (n = 276) received neoadjuvant chemoradiation, LNMs were classified according to the 6th UICC/TNM classification and systems based on the number (< or =4 and >4) or the ratio (< or =0.2 and >0.2) of LNMs. Survival of the respective stages, predictors of survival, and influence of both chemoradiation and number of examined LNs were studied. RESULTS: After a median follow-up of 50 months, the 5-year survival rates were 47% for the entire population, significantly poorer for patients with >4 LNMs (8% vs. 53%, P < 0.001) or a ratio of LNMs >0.2 (22% vs. 54%, P < 0.001). After adjustment for confounding variables, a number of LNMs >4 and a ratio of LNMs >0.2 were the only predictors of poor prognosis. The prognostic role of both the number and the ratio of LNMs was maintained whether patients received neoadjuvant chemoradiation or not. Moreover, LN ratio is shown to be more accurate for inadequately staged patients (<15 examined LNs), whereas the number of LNMs is pertinent for adequately staged patients (> or =15 examined LNs). CONCLUSION: Staging systems for esophageal cancer that use the number (< or =4 or >4) and the ratio (< or =0.2 or >0.2) of LNMs have greater prognostic importance than the current staging systems because of the good stratification of the groups and their clinical utility, taking into account neoadjuvant therapy and lymphadenectomy extent.

Activation of MUC1 mucin expression by bile acids in human esophageal adenocarcinomatous cells and tissues is mediated by the phosphatidylinositol 3-kinase.

BACKGROUND: In esophageal adenocarcinoma, MUC1 mucin expression increases in early stages of the carcinogenetic sequence, during which bile reflux has been identified as a major carcinogen. However, no link between MUC1 overexpression and the presence of bile acids in the reflux has been established so far, and molecular mechanisms regulating MUC1 expression during esophageal carcinogenetic sequence are unknown. Our aim was to identify (1) the bile acids able to upregulate MUC1 expression in esophageal cancer cells and mucosal samples, (2) the regulatory regions in MUC1 promoter responsive to bile acids, and (3) the signaling pathway(s) involved in this regulation. METHODS: MUC1 mRNA and mucin expression were studied by the means of real-time reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, both in the human esophageal OE33 adenocarcinoma cell line and in an ex vivo explant model. MUC1 promoter was cloned and transcription regulation was studied by transient cell transfection to identify the bile acid-responsive regions. Signaling pathways involved were identified using specific pharmacologic inhibitors and siRNA approach. RESULTS: Taurocholic, taurodeoxycholic, taurochenodeoxycholic, glycocholic, sodium glycocholate, and deoxycholic bile acids upregulated MUC1 mRNA and protein expression. The highest induction was obtained with deoxycholic and taurocholic acids in both cellular and explant models. The bile acid-mediated upregulation of MUC1 transcription occurs at the promoter level, with responsive elements located in the -1472/-234 region of the promoter, and involves the phosphatidylinositol 3-kinase signaling pathway. CONCLUSIONS: Bile acids induce MUC1 mucin overexpression in human esophageal adenocarcinoma cells and tissues by activating its transcription through a process involving phosphatidylinositol 3-kinase.

The safety of the same-day discharge for selected patients after laparoscopic fundoplication: a prospective cohort study.

BACKGROUND: We conducted a prospective cohort study to assess the acceptability, feasibility and safety of day-case laparoscopic fundoplication for gastroesophageal reflux disease in an university-based tertiary care center. METHODS: The procedure was proposed as routine for patients with proven symptomatic uncomplicated gastroesophageal reflux disease fulfilling predetermined inclusion criteria from September 2003 to December 2005. Standard anesthetic, surgical, analgesic, and antiemetic protocols were used. Acceptability, admission, complication, and reoperation rates and patient satisfaction were evaluated. Postoperative pain and nausea were assessed using an 11-point numeric rating scale (NRS). The Gastrointestinal Quality of Life Index (GIQLI) was administered before and after surgery. RESULTS: Among 100 patients screened, 40 (40%) were included. Seven patients were admitted because of inadequate pain control (n = 3), nausea or vomiting (n = 3), or anxiety (n = 1); 33 were discharged as planned 6 to 8 hours after operation. Only 1 patient was readmitted and reoperated because of fundoplicature migration following uncontrolled vomiting. At follow-up, 92.5% of patients were satisfied with the day-case treatment. If offered a similar operation in the future, 82.5% of patients would have accepted day-case treatment. The Gastrointestinal Quality of Life Index was 90.7 (+/-21.2) preoperatively compared with 105.8 (+/-21.8) postoperatively (P < .001). CONCLUSIONS: Day-case laparoscopic fundoplication is feasible in selected patients. However, (1) strict control of postoperative nausea and pain is essential, and (2) preoperative standardized education program for ambulatory surgery might be useful in order to enhance patient acceptability and satisfaction rates.