Summary Oesophageal carcinoma affects more than 450 000 people worldwide and the incidence is rapidly increasing. Squamous-cell carcinoma is the predominant form of oesophageal carcinoma worldwide, ...but a shift in epidemiology has been seen in Australia, the UK, the USA, and some western European countries (eg, Finland, France, and the Netherlands), where the incidence of adenocarcinoma now exceeds that of squamous-cell types. The overall 5-year survival of patients with oesophageal carcinoma ranges from 15% to 25%. Diagnoses made at earlier stages are associated with better outcomes than those made at later stages. In this Seminar we discuss the epidemiology, pathophysiology, diagnosis and staging, management, prevention, and advances in the treatment of oesophageal carcinoma.
Abstract Objectives Accurate cancer localization and negative resection margins are necessary for successful segmentectomy. In this study, we evaluate a newly developed software package that permits ...automated segmentation of the pulmonary parenchyma, allowing 3-dimensional assessment of tumor size, location, and estimates of surgical margins. Methods A pilot study using a newly developed 3-dimensional computed tomography analytic software package was performed to retrospectively evaluate preoperative computed tomography images of patients who underwent segmentectomy (n = 36) or lobectomy (n = 15) for stage 1 non–small cell lung cancer. The software accomplishes an automated reconstruction of anatomic pulmonary segments of the lung based on bronchial arborization. Estimates of anticipated surgical margins and pulmonary segmental volume were made on the basis of 3-dimensional reconstruction. Results Autosegmentation was achieved in 72.7% (32/44) of preoperative computed tomography images with slice thicknesses of 3 mm or less. Reasons for segmentation failure included local severe emphysema or pneumonitis, and lower computed tomography resolution. Tumor segmental localization was achieved in all autosegmented studies. The 3-dimensional computed tomography analysis provided a positive predictive value of 87% in predicting a marginal clearance greater than 1 cm and a 75% positive predictive value in predicting a margin to tumor diameter ratio greater than 1 in relation to the surgical pathology assessment. Conclusions This preoperative 3-dimensional computed tomography analysis of segmental anatomy can confirm the tumor location within an anatomic segment and aid in predicting surgical margins. This 3-dimensional computed tomography information may assist in the preoperative assessment regarding the suitability of segmentectomy for peripheral lung cancers.
Although anatomic segmentectomy has been considered a compromised procedure by many surgeons, recent retrospective, single-institution series have demonstrated tumor recurrence and patient survival ...rates that approximate those achieved by lobectomy. The primary objective of this study was to use propensity score matching to compare outcomes after these anatomic resection approaches for stage I non-small-cell lung cancer.
A retrospective data set including 392 segmentectomy patients and 800 lobectomy patients was used to identify matched segmentectomy and lobectomy cohorts (n = 312 patients per group) using a propensity score matching algorithm that accounted for confounding effects of preoperative patient variables. Primary outcome variables included freedom from recurrence and overall survival. Factors affecting survival were assessed by Cox regression analysis and Kaplan-Meier estimates.
Perioperative mortality was 1.2% in the segmentectomy group and 2.5% in the lobectomy group (P = .38). At a mean follow-up of 5.4 years, comparing segmentectomy with lobectomy, no differences were noted in locoregional (5.5% v 5.1%, respectively; P = 1.00), distant (14.8% v 11.6%, respectively; P = .29), or overall recurrence rates (20.2% v 16.7%, respectively; P = .30). Furthermore, when comparing segmentectomy with lobectomy, no significant differences were noted in 5-year freedom from recurrence (70% v 71%, respectively; P = .467) or 5-year survival (54% v 60%, respectively; P = .258). Segmentectomy was not found to be an independent predictor of recurrence (hazard ratio, 1.11; 95% CI, 0.87 to 1.40) or overall survival (hazard ratio, 1.17; 95% CI, 0.89 to 1.52).
In this large propensity-matched comparison, lobectomy was associated with modestly increased freedom from recurrence and overall survival, but the differences were not statistically significant. These results will need further validation by prospective, randomized trials (eg, Cancer and Leukemia Group B 140503 trial).
A more detailed understanding of the somatic genetic events that drive gastrointestinal adenocarcinomas is necessary to improve diagnosis and therapy. Using data from high-density genomic profiling ...arrays, we conducted an analysis of somatic copy-number aberrations in 486 gastrointestinal adenocarcinomas including 296 esophageal and gastric cancers. Focal amplifications were substantially more prevalent in gastric/esophageal adenocarcinomas than colorectal tumors. We identified 64 regions of significant recurrent amplification and deletion, some shared and others unique to the adenocarcinoma types examined. Amplified genes were noted in 37% of gastric/esophageal tumors, including in therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, suggesting the potential use of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers where targeted therapeutics have been less developed compared with colorectal cancers. Amplified loci implicated genes with known involvement in carcinogenesis but also pointed to regions harboring potentially novel cancer genes, including a recurrent deletion found in 15% of esophageal tumors where the Runt transcription factor subunit RUNX1 was implicated, including by functional experiments in tissue culture. Together, our results defined genomic features that were common and distinct to various gut-derived adenocarcinomas, potentially informing novel opportunities for targeted therapeutic interventions.
Outcomes after a decade of laparoscopic giant paraesophageal hernia repair Luketich, James D., MD; Nason, Katie S., MD, MPH; Christie, Neil A., MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
02/2010, Letnik:
139, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Objective Laparoscopic repair of giant paraesophageal hernia is a complex operation requiring significant laparoscopic expertise. Our objective was to compare our current approach and outcomes for ...laparoscopic repair of giant paraesophageal hernia with our previous experience. Methods A retrospective review of patients undergoing nonemergency laparoscopic repair of giant paraesophageal hernia, stratified by early versus current era (January 1997–June 2003 and July 2003–June 2008), was performed. We evaluated clinical outcomes, barium esophagogram, and quality of life. Results Laparoscopic repair of giant paraesophageal hernia was performed in 662 patients (median age 70 years, range 19–92 years) with a median percentage of herniated stomach of 70% (range 30%–100%). With time, use of Collis gastroplasty decreased (86% to 53%), as did crural mesh reinforcement (17% to 12%). Current era patients were 50% more likely to have a Charlson comorbidity index score greater than 3. Thirty-day mortality was 1.7% (11/662). Mortality and complication rates were stable with time, despite increasing comorbid disease in current era. Postoperative gastroesophageal reflux disease health-related quality of life scores were available for 489 patients (30-month median follow-up), with good to excellent results in 90% (438/489). Radiographic recurrence (15.7%) was not associated with symptom recurrence. Reoperation occurred in 3.2% (21/662). Conclusions With time, we have obtained significant minimally invasive experience and refined our approach to laparoscopic repair of giant paraesophageal hernia. Perioperative morbidity and mortality remain low, despite increased comorbid disease in the current era. Laparoscopic repair provided excellent patient satisfaction and symptom improvement, even with small radiographic recurrences. Reoperation rates were comparable to the best open series.
Regulatory T cells (T
cells) maintain host self-tolerance but are a major barrier to effective cancer immunotherapy. T
cells subvert beneficial anti-tumor immunity by modulating inhibitory receptor ...expression on tumor-infiltrating lymphocytes (TILs); however, the underlying mediators and mechanisms have remained elusive. Here, we found that the cytokines IL-10 and IL-35 (Ebi3-IL-12α heterodimer) were divergently expressed by T
cell subpopulations in the tumor microenvironment (TME) and cooperatively promoted intratumoral T cell exhaustion by modulating several inhibitory receptor expression and exhaustion-associated transcriptomic signature of CD8
TILs. While expression of BLIMP1 (encoded by Prdm1) was a common target, IL-10 and IL-35 differentially affected effector T cell versus memory T cell fates, respectively, highlighting their differential, partially overlapping but non-redundant regulation of anti-tumor immunity. Our results reveal previously unappreciated cooperative roles for T
cell-derived IL-10 and IL-35 in promoting BLIMP1-dependent exhaustion of CD8
TILs that limits effective anti-tumor immunity.
Chylothorax is a rare but potentially lethal complication of esophagectomy. This study evaluated the rate of postesophagectomy chylothorax, identified associated risk factors, and compared ...postoperative outcomes in patients with and without chylothorax.
We reviewed 892 consecutive patients who underwent esophagectomy (1997 to 2008). Preoperative, operative, and postoperative details, including adverse outcomes and mortality, were analyzed.
Postesophagectomy chylothorax occurred in 34 patients (3.8%). Chylothorax was significantly associated with 30-day major complications (85% vs 46%; p<0.001), including an increased likelihood of sepsis (p=0.001), pneumonia (p=0.009), reintubation (p=0.002) or reoperation (p<0.001), and death (17.7% vs 3.9%, p<0.001). Median length of stay was 17 vs 8 days (p=0.005). Median time to chylothorax diagnosis was 5 days. Thoracic duct ligation was performed in 21 (62%) at a median 13 days after esophagectomy. Two patients required repeat duct ligation for persistent chylothorax. Squamous cell cancer histology (9 of 34; 26%) was an independent predictor of postoperative chylothorax (odds ratio, 4.18; 95% confidence interval, 1.39 to 12.6). Odds of chylothorax were 36 times greater with average daily chest tube output exceeding 400 mL in the first 6 postoperative days (odds ratio, 35.9; 95% confidence interval, 8.2 to 157.8).
Postoperative chylothorax is associated with significant postoperative morbidity and mortality. Patients with squamous cell cancer may be at increased risk. In addition, average daily chest tube output exceeding 400 mL in the early postoperative period should prompt fluid analysis for chylothorax to facilitate early diagnosis and consideration of thoracic duct ligation.
Segmentectomy for early-stage non-small cell lung cancer (NSCLC) remains controversial and has been previously associated with high local recurrence rates. We compared the outcomes of anatomic ...segmentectomy with lobectomy for stage I NSCLC and investigated the impact of surgical resection margins on recurrence.
From 2002 to 2006, 182 anatomic segmentectomies (114 open, 68 video-assisted thoracic surgery VATS), were performed for stage 1A (n = 109) or IB (n = 73) NSCLC. These were compared with 246 lobectomies (1A, 114; 1B, 132). Variables analyzed included hospital course, mortality, and patterns of recurrence and survival.
All segmentectomy surgical margins were free of tumor (average margin, 18.2 mm). Operative time (147 versus 216 minutes; p < 0.0001) and estimated blood loss (185 versus 291 mL; p = 0.0003) were significantly reduced after segmentectomy compared with lobectomy. Thirty-day mortality (1.1% versus 3.3%), total complications, disease-free recurrence, and survival were similar between segmentectomy and lobectomy at a mean follow-up of 18.1 and 28.5 months, respectively. There were 32 recurrences after segmentectomy (17.6%) at a mean of 14.3 months (14 locoregional 7.7%, 18 distant 9.9%), and 89% of recurrences were seen when tumor margins were 2 cm or less. Margin/tumor diameter ratios exceeding 1 were associated with a significant reduction in recurrence rates compared with ratios of less than 1 (25.0% versus 6.2%; p = 0.0014).
Anatomic segmentectomy can be performed safely by an open or VATS approach. Segmentectomy outcomes compare favorably with standard lobectomy for stage I NSCLC. Margin/tumor ratios of less than 1 are associated with a higher rate of recurrence. Lobectomy should be considered as primary therapy when such margins are not obtainable with segmentectomy in the good-risk patient.
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