Carlo Castoro

Trends in management and prognosis for esophageal cancer surgery: twenty-five years of experience at a single institution.

OBJECTIVE To investigate trends in results of esophagectomies to treat esophageal cancer at a single high-volume institution during the past 25 years. DESIGN AND SETTING Retrospective cohort study in a university tertiary referral center. PATIENTS AND METHODS Patients with cancer of the thoracic esophagus or esophagogastric junction seen from 1980 through 2004 were included (N = 3493). Three time periods were defined: 1980-1987, 1988-1995, and 1996-2004. MAIN OUTCOME MEASURES Clinical presentation, tumor characteristics, and morbidity, mortality, and survival rates among patients with esophageal cancer undergoing esophagectomy. RESULTS The ratio of squamous cell carcinoma to adenocarcinoma decreased from 3.3 to 1.7 (P <.001) during the study period, in parallel with an increase in the number of patients with tumors in the lower esophagus/esophagogastric junction. An increasing proportion of patients who underwent resection received neoadjuvant treatment (chemotherapy/chemoradiotherapy), and 1978 patients underwent esophagectomy. The R0 resection rate increased from 74.5% to 90.1% (P <.001). In addition, an increasing proportion of patients had early-stage tumor in the resected specimen. In-hospital postoperative mortality decreased from 8.2% to 2.6% (P <.001), and the 5-year survival rate significantly improved from 18.8% to 42.3% (P <.001) for all patients who underwent resection. Pathological tumor stage, completeness of the resection, time period, sex, tumor histological type, and tumor location influenced the prognosis of patients with esophageal cancer undergoing esophagectomy. CONCLUSIONS A change in location and histological type of esophageal cancer has occurred during the past 25 years. Earlier diagnosis, a multidisciplinary approach, and refinements in surgical technique and perioperative care have led to a significant reduction in postoperative mortality rate and improved long-term survival among patients with cancer of the thoracic esophagus or esophagogastric junction.

Systematic review of health-related quality of life after esophagectomy for esophageal cancer

This study is aimed to assess the long-term health-related quality of life (HRQL) of patients after esophagectomy for esophageal cancer in comparison with established norms, and to evaluate changes in HRQL during the different stages of follow-up after esophageal resection. A systematic review was performed by searching medical databases (Medline, Embase and the Cochrane Library) for potentially relevant studies that appeared between January 1975 and March 2011. Studies were included if they addressed the question of HRQL after esophageal resection for esophageal cancer. Two researchers independently performed the study selection, data extraction and analysis processes. Twenty-one observational studies were included with a total of 1282 (12-355) patients. Five studies were performed with short form-36 (SF-36) and 16 with European Organization for Research and Treatment of Cancer (EORTC) QLQ C30 (14 of them also utilized the disease-specific OES18 or its previous version OES24). The analysis of long-term generic HRQL with SF-36 showed pooled scores for physical, role and social function after esophagectomy similar to United States norms, but lower pooled scores for physical function, vitality and general health perception. The analysis of HRQL conducted using the Global EORTC C30 global scale during a 6-mo follow-up showed that global scale and physical function were better at the baseline. The symptom scales indicated worsened fatigue, dyspnea and diarrhea 6 mo after esophagectomy. In contrast, however, emotional function had significantly improved after 6 mo. In conclusion, short- and long-term HRQL is deeply affected after esophagectomy for cancer. The impairment of physical function may be a long-term consequence of esophagectomy involving either the respiratory system or the alimentary tract. The short- and long-term improvement in the emotional function of patients who have undergone successful operations may be attributed to the impression that they have survived a near-death experience.

Single-layered cervical esophageal anastomoses: A prospective study of two suturing techniques

We carried out a prospective, randomized study over a 1-year period to compare the efficacy of a single layer of continuous absorbable monofilament (Maxon) with that of a single layer of interrupted Polyglactin sutures (Vicryl) in the performance of cervical esophagogastric anastomoses. Forty-two consecutive patients with carcinoma of the esophagus or cardia, in whom the stomach was transposed through the mediastinal route after esophagectomy, were enrolled in the study. There were 21 patients in each group. There was no hospital mortality. One asymptomatic anastomotic leak and two early anastomotic strictures requiring dilation occurred in patients in whom an interrupted technique was employed. The continuous technique required significantly less operative time (p < 0.0001), and the cost of the suture material was reduced markedly. We conclude that either a continuous or an interrupted monolayer esophagogastric anastomosis can give satisfactory results after esophagectomy for cancer, provided that the vascular supply to the gastric fundus is maintained adequately. The continuous technique has the advantages of being time-saving, cheaper, and easier to perform and to teach.

Effects of Neoadjuvant Therapy on Perioperative Morbidity in Elderly Patients Undergoing Esophagectomy for Esophageal Cancer

BackgroundThe use of cytoreductive therapy followed by surgery is preferred by many centers dealing with locally advanced esophageal cancer. However, the potential for increase in mortality and morbidity rates has raised concerns on the use of chemoradiation therapy, especially in elderly patients. The aim of this study was to assess the effects of induction therapy on postoperative mortality and morbidity in elderly patients undergoing esophagectomy for locally advanced esophageal cancer at a single institution.MethodsPostoperative mortality and morbidity of patients ≥70 years old undergoing esophagectomy after neoadjuvant therapy, between January 1992 and October 2005 for cancer of the esophagus or esophagogastric junction, were compared with findings in younger patients also receiving preoperative cytoreductive treatments.Results818 patients underwent esophagectomy during the study period. The study population included 238 patients <70 years and 31 ≥70 years old undergoing esophageal resection after neoadjuvant treatment. Despite a significant difference in comorbidities (pulmonary, cardiological and vascular), postoperative mortality and morbidity were similar irrespective of age.ConclusionsElderly patients receiving neoadjuvant therapies for cancer of the esophagus or esophagogastric junction do not have a significantly increased prevalence of mortality and major postoperative complications, although cardiovascular complications are more likely to occur. Advanced age should no longer be considered a contraindication to preoperative chemoradiation therapy preceding esophageal resection in carefully selected fit patients.

Interval Between Neoadjuvant Chemoradiotherapy and Surgery for Squamous Cell Carcinoma of the Thoracic Esophagus Does Delayed Surgery Have an Impact on Outcome

Objective:Aim of this study was to evaluate whether delayed surgery after neoadjuvant chemoradiotherapy (CRT) affects postoperative outcomes in patients with locally advanced squamous cell carcinoma (SCC) of the thoracic esophagus. Background:Esophagectomy is usually recommended within 4 to 6 weeks after completion of neoadjuvant CRT. However, the optimal timing of surgery is not clearly defined. Methods:A total of 129 consecutive patients with locally advanced esophageal cancer, treated between 1998 and 2007, were retrospectively analyzed using prospectively collected data. Patients were divided into 3 groups on the basis of timing to surgery: group 1, ⩽30 days (n = 17); group 2, 31 to 60 days (n = 83); and group 3, 61 to 90 days (n = 29). Subsequently, only 2—numerically more consistent—groups were studied, using the median value of timing intervals as a cutoff level: group A, ⩽46 days (n = 66); and group B, >46 days (n = 63). Results:Groups were comparable in terms of patient and tumor characteristics, type of neoadjuvant regimen, toxicity, postoperative morbidity and mortality rates, tumor downstaging, and pathologic complete responses. The overall 5-year actuarial survival rate was 0% in group 1, 43.1% in group 2, and 35.9% in group 3 (P = 0.13). After R0 resection (n = 106), the 5-year actuarial survival rate was 0%, 51%, and 47.3%, respectively (P = 0.18). Tumor recurrence after R0 resection seemed to be inversely related, even if not significantly (P = 0.17), to the time interval between chemoradiation and surgery: 50% in group 1, 40.6% in group 2, and 21.7% in group 3. When considering only 2 groups, the overall 5-year survival was 33.1% in group A and 42.7% in group B (P = 0.64); after R0 resection, the 5-year survival was 37.8% and 56.3%, respectively (P = 0.18). The rate of tumor recurrence was significantly lower in group B (25%) than in group A (48.3%) (P = 0.02). Conclusion:Delayed surgery after neoadjuvant chemoradiation does not compromise the outcomes of patients with locally advanced SCC of the esophagus. Delaying surgery up to 90 days offers relevant advantages in the clinical management of the patients, can reduce tumor recurrences, and may improve prognosis after complete R0 resection surgery.

Quality of life in patients with esophageal stenting for the palliation of malignant dysphagia

Incidence of esophageal cancer (EC) is rising more rapidly in the Western world than that of any other cancer. Despite advances in therapy, more than 50% of patients have incurable disease at the time of presentation. This precludes curative treatment and makes palliative treatment a more realistic option for most of these patients. Dysphagia is the predominant symptom in more than 70% of patients with EC and although several management options have been developed in recent years to palliate this symptom, the optimum management is not established. Self-expanding metal stents (SEMS) are a well-established palliation modality for dysphagia in such patients. Health-related quality of life (HRQoL) is becoming a major issue in the evaluation of any therapeutic or palliative intervention. To date, only a few published studies can be found on Medline examining HRQoL in patients with advanced EC treated with SEMS implantation. The aim of this study was to review the impact on HRQoL of SEMS implantation as palliative treatment in patients with EC. All Medline articles regarding HRQoL in patients with advanced EC, particularly those related to SEMS, were reviewed. In most studies, relief of dysphagia was the only aspect of HRQoL being measured and SEMS implantation was compared with other palliative treatments such as brachytherapy and laser therapy. SEMS insertion provides a swift palliation of dysphagia compared to brachytherapy and no evidence was found to suggest that stent implantation is different to laser treatment in terms of improving dysphagia, recurrent dysphagia and better HRQoL, although SEMS insertion has a better technical success rate and also reduces the number of repeat interventions.

Inflammatory colonic carcinogenesis: A review on pathogenesis and immunosurveillance mechanisms in ulcerative colitis

Ulcerative colitis (UC) is characterized by repeated flare-ups of inflammation that can lead to oncogenic insults to the colonic epithelial. UC-associated carcinogenesis presents a different sequence of tumorigenic events compared to those that contribute to the development of sporadic colorectal cancer. In fact, in UC, the early events are represented by oxidative DNA damage and DNA methylation that can produce an inhibition of oncosuppressor genes, mutation of p53, aneuploidy, and microsatellite instability. Hypermethylation of tumor suppressor and DNA mismatch repair gene promoter regions is an epigenetic mechanism of gene silencing that contribute to tumorigenesis and may represent the first step in inflammatory carcinogenesis. Moreover, p53 is frequently mutated in the early stages of UC-associated cancer. Aneuploidy is an independent risk factor for forthcoming carcinogenesis in UC. Epithelial cell-T-cell cross-talk mediated by CD80 is a key factor in controlling the progression from low to high grade dysplasia in UC-associated carcinogenesis.

The HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesis ☆,☆☆

A subset of gastric (intestinal-type) and esophageal (Barrett) adenocarcinoma features HER2 protein overexpression. Consistent evidence demonstrates that microRNAs have a major role in HER2 (dys)regulation. MiR-125a-5p and miR125b expressions were tested in the spectrum of lesions in the gastroesophageal carcinogenic cascade, also correlating miR-125a-5p/125b levels with HER2 status. MiR-125a-5p and miR-125b expression (quantitative reverse transcriptase polymerase chain reaction [qRT-PCR]) and HER2 status (immunohistochemistry [IHC] and chromogenic in situ hybridization [CISH]) were assessed in a series of 90 biopsy samples spanning the whole histologic spectrum of gastric and esophageal carcinogenesis. To support the obtained results, the qRT-PCR levels of microRNAs and their expression (in situ hybridization) were tested in an adjunctive series of gastric and esophageal adenocarcinoma, including (IHC/CISH validated) HER2-negative and HER2-positive cases. Both miR-125a-5p and miR-125b levels were significantly down-regulated throughout the gastric and esophageal carcinogenic cascade. HER2 status (IHC and CISH) correlated inversely with miR-125 expression (qRT-PCR and in situ hybridization). Dysregulation of miR-125a-5p/125b and HER2 is an early event in the gastric (intestinal-type) and esophageal (Barrett) oncogenesis. In both oncogenetic cascades, miR-125 expression correlates inversely with HER2 status. MiR-125a-5p/125b can be considered among the therapeutic targets in HER2-positive esophageal and gastric adenocarcinoma.

Prophylactic Thoracic Duct Mass Ligation Prevents Chylothorax After Transthoracic Esophagectomy for Cancer

BackgroundChylothorax after transthoracic esophagectomy for cancer is an uncommon but potentially life-threatening postoperative complication. It has been reported that preventive thoracic duct ligation can reduce the incidence of postoperative chylothorax after esophagectomy for cancer. In this prospective series, we evaluated the results of preventive intraoperative thoracic duct mass ligation in patients who underwent transthoracic esophagectomy for cancer.MethodsFrom 2001 to 2006, 323 patients underwent transthoracic esophagectomy for cancer and duct ligation during the operation was routinely performed.ResultsNo intraoperative or postoperative complications directly related to the procedure were recorded. No postoperative chylothorax was observed.ConclusionsIn this series, the technique of intraoperative thoracic duct mass ligation proved to be safe and effectively prevented postoperative chylothorax in patients who underwent transthoracic esophagectomy for cancer.

Human epithelial growth factor receptor 2 (HER2) status in primary and metastatic esophagogastric junction adenocarcinomas

Differences in human epithelial growth factor receptor 2 dysregulation in primary solid tumors and metastases may (at least partially) explain human epithelial growth factor receptor 2-targeted therapeutic inconsistencies. Human epithelial growth factor receptor 2 status was tested in a series of 47 radically treated consecutive esophagogastric junction adenocarcinomas (male/female, 38/9; mean age, 67.9 years) in both primary cancers and paired synchronous nodal metastases. None of the patients received neoadjuvant therapy. For each case, 2 nonadjacent tissue samples from primary esophagogastric junction adenocarcinoma and 2 different metastatic nodes were considered (188 tissue samples in all). Human epithelial growth factor receptor 2 status was assessed by immunohistochemistry (PATHWAY-HER2/neu [4B5]; Ventana Medical Systems, Milan, Italy) and dual chromogenic in situ hybridization (duoCISH; DAKO, Glostrup, Denmark). Immunohistochemistry staining scores were nil in 22 tumors (47%), 1 (21%) in 10, 2 (13%) in 6, and 3 (19%) in 9. Human epithelial growth factor receptor 2 gene amplification (25.5%) was associated with more differentiated phenotype (Fisher exact test, P = .039) and advanced tumor stage (Fisher exact test, P = .015). Significant agreement was observed between human epithelial growth factor receptor 2 protein expression (immunohistochemistry) and human epithelial growth factor receptor 2 genes amplification (chromogenic in situ hybridization) (κ = 0.84, P < .001). Both immunohistochemistry and chromogenic in situ hybridization documented an excellent intratumor agreement in human epithelial growth factor receptor 2 status (κ = 0.75, P < .001; κ = 0.88, P < .001, respectively). Human epithelial growth factor receptor 2 status was comparable in primary versus metastatic nodal cancers by both immunohistochemistry and chromogenic in situ hybridization (Cohen Φ, both P < .001). In esophagogastric junction adenocarcinomas, human epithelial growth factor receptor 2 status (as assessed by immunohistochemistry and/or chromogenic in situ hybridization) is virtually unaffected by intratumor variability; it is consistent with findings in nodal metastases, and it reliably identifies patients with esophagogastric junction adenocarcinoma eligible for anti-human epithelial growth factor receptor 2 therapy.