Rita Alfieri

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.

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.

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.

Totally implantable venous access devices: retrospective analysis of different insertion techniques and predictors of complications in 796 devices implanted in a single institution

BackgroundThe aim of this study was to assess the efficacy and safety of totally implanted vascular devices (TIVAD) using different techniques of insertion.MethodsWe performed a retrospective study using a prospective collected database of 796 consecutive oncological patients in which TIVADs were inserted. We focused on early and late complications following different insertion techniques (surgical cutdown, blind and ultrasound guided percutaneous) according to different techniques.ResultsUltrasound guided technique was used in 646 cases, cephalic vein cutdown in 102 patients and percutaneous blind technique in 48 patients. The overall complication rate on insertion was 7.2% (57 of 796 cases). Early complications were less frequent using the ultrasound guided technique: arterial puncture (p = 0.009), technical failure (p = 0.009), access site change after first attempt (p = 0.002); pneumothorax occurred in 4 cases, all using the blind percutaneus technique. Late complications occurred in 49 cases (6.1%) which required TIVAD removal in 43 cases and included: sepsis (29 cases), thrombosis (3 cases), dislocation (7 cases), skin dehiscence (3 cases), and severe pain (1 case).ConclusionUltrasound guided technique is the safest option for TIVAD insertion, with the lowest rates of immediate complications.

ERCC1 C8092A (rs3212986) polymorphism as a predictive marker in esophageal cancer patients treated with cisplatin/5-FU-based neoadjuvant therapy.

Objective At present, no consensus exists on the beneficial effect of preoperative cisplatin/5-fluorouracil (5-FU)-based chemotherapy versus primary surgery in the management of patients with esophageal cancer. The aim of this study was to evaluate the impact of some relevant genetic polymorphisms, within drug-related and DNA repair genes, on the clinical outcome of esophageal cancer patients subjected to cisplatin/5-FU-based neoadjuvant treatment. Methods DNA from 143 esophageal cancer patients, 63 receiving neoadjuvant therapy and 80 receiving primary surgery, was analyzed for the following polymorphisms: the GSTM1 null, GSTT1 null, and GSTP1 Ile105Val (rs16953) in glutathione S-transferase (GST) family, 2 in thymidylate synthase (TS) gene, and the ERCC1 Asn118Asn (rs11615), ERCC1 C8092A (rs3212986), XPD/ERCC2 Asp312Asn (rs1799793), and XPD/ERCC2 Lys751Gln (rs13181) of the nucleotide excision repair pathway. Results We found that the ERCC1 rs3212986, although not associated with therapeutic response, is an independent predictive marker of better outcome in a cisplatin/5-FU-based neoadjuvant setting (hazard ratio: 0.38, 95% confidence interval: 0.2–0.73, P=0.008). In contrast, no association with clinical outcome was observed for this polymorphism in the primary surgery group. Conclusion Our study indicates the ERCC1 rs3212986 as a predictive marker in the cisplatin/5-FU-based neoadjuvant setting, and also suggests its use as a marker to select the appropriate therapeutic approach in esophageal cancer patients.

Postoperative outcome after oesophagectomy for cancer: Nutritional status is the missing ring in the current prognostic scores

BACKGROUND Several prognostic scores were designed in order to estimate the risk of postoperative adverse events. None of them includes a component directly associated to the nutritional status. The aims of the study were the evaluation of performance of risk-adjusted models for early outcomes after oesophagectomy and to develop a score for severe complication prediction with special consideration regarding nutritional status. METHODS A comparison of POSSUM and Charlson score and their derivates, ASA, Lagarde score and nutritional index (PNI) was performed on 167 patients undergoing oesophagectomy for cancer. A logistic regression model was also estimated to obtain a new prognostic score for severe morbidity prediction. RESULTS Overall morbidity was 35.3% (59 cases), severe complications (grade III-V of Clavien-Dindo classification) occurred in 20 cases. Discrimination was poor for all the scores. Multivariable analysis identified pulse, connective tissue disease, PNI and potassium as independent predictors of severe morbidity. This model showed good discrimination and calibration. Internal validation using standard bootstrapping techniques confirmed the good performance. CONCLUSIONS Nutrition could be an independent risk factor for major complications and a nutritional status coefficient could be included in current prognostic scores to improve risk estimation of major postoperative complications after oesophagectomy for cancer.

Genetic Features of Metachronous Esophageal Cancer Developed in Hodgkin’s Lymphoma or Breast Cancer Long-Term Survivors: An Exploratory Study

Background Development of novel therapeutic drugs and regimens for cancer treatment has led to improvements in patient long-term survival. This success has, however, been accompanied by the increased occurrence of second primary cancers. Indeed, patients who received regional radiotherapy for Hodgkin’s Lymphoma (HL) or breast cancer may develop, many years later, a solid metachronous tumor in the irradiated field. Despite extensive epidemiological studies, little information is available on the genetic changes involved in the pathogenesis of these solid therapy-related neoplasms. Methods Using microsatellite markers located in 7 chromosomal regions frequently deleted in sporadic esophageal cancer, we investigated loss of heterozygosity (LOH) and microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty samples were of esophageal carcinoma developed in HL or breast cancer long-term survivors: 14 squamous cell carcinomas (ESCC) and 6 adenocarcinomas (EADC), while 26 samples, used as control, were of sporadic esophageal cancer (15 ESCC and 11 EADC). Results We found that, though the overall LOH frequency at the studied chromosomal regions was similar among metachronous and sporadic tumors, the latter exhibited a statistically different higher LOH frequency at 17q21.31 (p = 0.018). By stratifying for tumor histotype we observed that LOH at 3p24.1, 5q11.2 and 9p21.3 were more frequent in ESCC than in EADC suggesting a different role of the genetic determinants located nearby these regions in the development of the two esophageal cancer histotypes. Conclusions Altogether, our results strengthen the genetic diversity among ESCC and EADC whether they occurred spontaneously or after therapeutic treatments. The presence of histotype-specific alterations in esophageal carcinoma arisen in HL or breast cancer long-term survivors suggests that their transformation process, though the putative different etiological origin, may retrace sporadic ESCC and EADC carcinogenesis.

Iterated combination-based paired permutation tests to determine shape effects of chemotherapy in patients with esophageal cancer

The nonparametric combination of dependent permutation tests method is a useful general tool when a testing problem can be broken down into a set of different k > 1 partial tests. These partial tests, after adjustment of p-values to control for multiplicity, can be marginally analyzed, but jointly considered they can provide information on an overall hypothesis, which might represent the true goal of the testing problem. On the one hand, independence among the partial tests is usually an unrealistic assumption; on the other, even when the underlying dependence relations are known quite often they are difficult to cope with properly. Therefore this combination must be achieved nonparametrically, by implicitly taking into account the dependence structure of tests without explicitly describing it. An important property of the tests based on nonparametric combination methodology, when the number of response variables is high compared to the sample sizes, consists in the finite sample consistency. A practical problem involves choosing the most suitable combining function for each specific testing problem given that the final result can be affected by this crucial choice. The purpose of this article is to present an nonparametric combination solution based on the iterated combination of partial tests, evaluate its power behavior using a Monte Carlo simulation study and apply it to a real medical problem, namely the evaluation of the effects of chemotherapy on the shape of esophageal tumors. R code has been implemented to carry out the analyses.

Hybrid minimally invasive esophagectomy for cancer: impact on postoperative inflammatory and nutritional status

The purpose of this case-control study was to evaluate the impact of hybrid minimally invasive esophagectomy for cancer on surgical stress response and nutritional status. All 34 consecutive patients undergoing hybrid minimally invasive esophagectomy for cancer at our surgical unit between 2008 and 2013 were retrospectively compared with 34 patients undergoing esophagectomy with open gastric tubulization (open), matched for neoadjuvant therapy, pathological stage, gender and age. Demographic data, tumor features and postoperative course (including quality of life and systemic inflammatory and nutritional status) were compared. Postoperative course was similar in terms of complication rate. Length of stay in intensive care unit was shorter in patients undergoing hybrid minimally invasive esophagectomy (P = 0.002). In the first postoperative day, patients undergoing hybrid minimally invasive esophagectomy had lower C-reactive protein levels (P = 0.001) and white cell blood count (P = 0.05), and higher albumin serum level (P = 0.001). In this group, albumin remained higher also at third (P = 0.06) and seventh (P = 0.008) postoperative day, and C-reactive protein resulted lower at third post day (P = 0.04). Hybrid minimally invasive esophagectomy significantly improved the systemic inflammatory and catabolic response to surgical trauma, contributing to a shorter length of stay in intensive care unit.