Perioperative benefit and outcome of thoracic epidural in esophageal surgery: a clinical review.

Surgery for esophageal cancer is a highly stressful and painful procedure, and a significant amount of analgesics may be required to eliminate perioperative pain and blunt the stress response to surgery. Proper management of postoperative pain has invariably been shown to reduce the incidence of postoperative complications and accelerate recovery. Neuraxial analgesic techniques after major thoracic and upper abdominal surgery have long been established to reduce respiratory, cardiovascular, metabolic, inflammatory, and neurohormonal complications.The aim of this review is to evaluate and discuss the relevant clinical benefits and outcome, as well as the possibilities and limits of thoracic epidural anesthesia/analgesia (TEA) in the setting of esophageal resections. A comprehensive search of original articles was conducted investigating relevant literature on MEDLINE, Cochrane reviews, Google Scholar, PubMed, and EMBASE from 1985 to July2017. The relationship between TEA and important endpoints such as the quality of postoperative pain control, postoperative respiratory complications, surgical stress-induced immunosuppression, the overall postoperative morbidity, length of hospital stay, and major outcomes has been explored and reported. TEA has proven to enable patients to mobilize faster, cooperate comfortably with respiratory physiotherapists and achieve satisfactory postoperative lung functions more rapidly. The superior analgesia provided by thoracic epidurals compared to that from parenteral opioids may decrease the incidence of ineffective cough, atelectasis and pulmonary infections, while the associated sympathetic block has been shown to enhance bowel blood flow, prevent reductions in gastric conduit perfusion, and reduce the duration of ileus. Epidural anesthesia/analgesia is still commonly used for major 'open' esophageal surgery, and the recognized advantages in this setting are soundly established, in particular as regards the early recovery from anesthesia, the quality of postoperative pain control, and the significantly shorter duration of postoperative mechanical ventilation. However, this technique requires specific technical skills for an optimal conduction and is not devoid of risks, complications, and failures.

Genetic risk of subsequent esophageal cancer in lymphoma and breast cancer long-term survival patients: a pilot study.

The occurrence of a second primary esophageal carcinoma (EC) in long-term cancer survivors may represent a late effect of previous radio-chemotherapeutic treatment. To identify the genetic factors that could increase this risk, we analyzed nine variants within ERCC1, XPD, XRCC1 and XRCC3 DNA repair pathway genes, and GSTP1, TP53 and MDM2 genes in 61 patients who received radio-chemotherapy for a prior lymphoma or breast cancer; 29 of them had a second primary EC. This cohort consists of 22 esophageal squamous cell carcinoma (ESCC) and 7 esophageal adenocarcinoma (EADC) patients. A validation cohort of 154 patients with sporadic EC was also included. The XPD Asp312Asn (rs1799793) was found to be associated with the risk of developing second primary ESCC (P=0.015). The resultant variant was also involved in the onset of sporadic ESCC (P=0.0018). To know in advance who among long-term cancer survivors have an increased risk of EC could lead to a more appropriate follow-up strategy.

Effect of preoperative chemoradiotherapy on outcome of patients with locally advanced esophagogastric junction adenocarcinoma-a pilot study.

BACKGROUND: To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered; indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. METHODS: We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin-5-fluorouracil-oxaliplatin) for 4 cycles, and concurrent computed tomography-based three-dimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. RESULTS: All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. CONCLUSIONS: In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response.

A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer.

BACKGROUND: Preoperative chemoradiotherapy (CRT) improves the survival of patients with oesophageal cancer when compared with surgery alone. METHODS: We conducted a phase II, multicenter trial of FOLFOX-4 and cetuximab in patients with locally advanced oesophageal cancer (LAEC) followed by daily radiotherapy (180 cGy fractions to 5040 cGy) with concurrent weekly cetuximab. Cytokines levels potentially related to cetuximab efficacy were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, at week 8 and at week 17. Primary end point was complete pathological response rate (pCR). RESULTS: In all, 41 patients were enroled. Among 30 patients who underwent surgery, a pCR was observed in 8 patients corresponding to a rate of 27%. The most frequent grade 3/4 toxicity was skin (30%) and neutropenia (30%). The 36-month survival rates were 85 and 52% in patients with pathological CR or PR vs 38 and 33% in patients with SD or PD. CONCLUSIONS: Incorporating cetuximab into a preoperative regimen for LAEC is feasible; no correlation between cytokines changes and patient outcome was observed. Positron emission tomography/computed tomography study even if influenced by the small number of patients appears to be able to predict patients outcome both as early and late metabolic response.

Pseudoachalasia: not only esophago-gastric cancer.

Pseudoachalasia is a rare clinical entity which has clinical, radiographic and manometric features often indistinguishable from achalasia. A small primary adenocarcinoma arising at the gastroesophageal junction or a tumor of the distal esophagus are the most frequent causes. Rarely, processes other than esophagogastric cancers may lead to the development of pseudoachalasia. We present three cases of pseudoachalasia in which the primary cause of the disease was not an esophagogastric cancer. The causes were a pancreatic carcinoma, a breast cancer and an histiocytosis X. Aspects of these three patients' diagnostic and therapeutic course are discussed in detail.

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer.

This study was performed to assess the efficacy and safety of docetaxel, cisplatin and fluorouracil combination in patients with unresectable locally advanced oesophageal squamous cell carcinoma. Treatment consisted of docetaxel 60 mg m(-2), cisplatin 75 mg m(-2) on day 1 and fluorouracil 750 mg m(-2) day(-1) on days 2-5, repeated every 3 weeks for three cycles, followed by carboplatin 100 mg m(-2) week(-1) for 5 weeks and concurrent radiotherapy (45 Gy in 25 fractions, 5 days week(-1)). After radiotherapy, eligible patients either underwent an oesophagectomy or received high dose rate endoluminal brachytherapy (HDR-EBT). Thirty-one out of 37 enrolled patients completed the planned chemotherapy and 30 completed chemoradiation. After completion of chemotherapy, 49% (95% CI: 32.2-66.2) had a clinical response. Twelve patients (32%) underwent a resection, which was radical in 60% (postoperative mortality: 0%). A pathological complete response was documented in four patients (11% of enrolled, 30% of resected). The median survival was 10.8 months (95% CI: 8.1-12.4), and the 1- and 2-year survival rates were 35.1 and 18.9%, respectively. Grade 3-4 toxicities were neutropoenia 32%, anaemia 11%, non-neutropoenic infections 18%, diarrhoea 6% and oesophagitis 5%. Nine patients (24%) developed a tracheo-oesophageal fistula during treatment. Even if the addition of docetaxel to cisplatin and 5-fluorouracil (5-FU) seems to be more active than the cisplatin and 5-FU combination, an incremental improvement in survival is not seen, and the toxicity observed in this study population is of concern. In order to improve the prognosis of these patients, new drugs, combinations and strategies with a better therapeutic index need to be identified.

Multimodal imaging of esophagus and cardia cancer before and after treatment.

PURPOSE: Prognosis and treatment of esophagus and cardia cancer (ECC) depend on the precision with which the disease is staged according to the American Joint Committee of Cancer (AJCC) criteria. Imaging modalities normally used in clinical staging are esophagography, esophagoscopy, endoscopic ultrasound (EUS), computed tomography (CT) and positron emission tomography- CT fusion (CT-PET). The combination of these methods is crucial in determining not only the right diagnosis but also the stage and follow-up after multimodal treatment. The purpose of our investigation was to define the role of each imaging modality in determining the most appropriate treatment options in patients with ECC. MATERIALS AND METHODS: Fifty-six patients with ECC diagnosed by X-ray of the upper digestive tract, endoscopy and biopsy were staged using EUS, chest and abdomen CT scan, and CT-PET. Thirty-four patients in stage II and 18 patients in stage III underwent surgery after neoadjuvant chemotherapy; four patients in stage IV were treated with the positioning of an endoprosthesis after chemoradiotherapy. In the 52 patients who had surgery, follow-up included digestive tract X-ray, endoscopy and CT of the chest and abdomen every 6-8 months for the first 3 years. CT-PET was only performed in patients with a clinical suspicion of recurrence and/or CT findings suspicious of persistent disease (12 cases). RESULTS: In all 56 patients, endoscopy, EUS, CT and CT-PET in combination were crucial in determining the site of disease, locoregional extent and depth of esophageal wall penetration (T), and any involvement of the mediastinal lymph nodes (N1), extrathoracic lymph nodes (M1) or hepatic metastases. In the locoregional staging of ECC before chemotherapy, we were able to differentiate T2-T3 from T4 in 40 patients; T4 disease was found in 12 potentially resectable cases. We were able to distinguish N0 from N1 in 12 patients. In four cases, the presence of small lymph node and/or liver metastases prompted positioning of an endoprosthesis. The specificity of CT in detecting small lymph nodes in the mediastinum was less than 50% while for CT-PET, it was more than 80%; EUS revealed sensitivity higher than 90% but a low specificity in seven cases. Only CT-PET revealed metastatic subdiaphragmatic lymph nodes (diameter <15 mm) in three cases. Presurgical restaging of the 18 patients (stage III) who had chemotherapy was based on endoscopy, EUS, CT of the chest and abdomen and CT-PET (only in suspected cases) and was compatible with surgery. Anastomotic recurrence was diagnosed in 16 patients by endoscopy with associated biopsy; any intramediastinal spread from anastomotic recurrences was evaluated by chest CT, and CT-PET in suspected cases. CONCLUSIONS: X-ray of the upper digestive tract and chest and abdomen CT scan are useful in preliminary evaluation of ECC. Endoscopy is particularly indicated for evaluating tumour morphology, taking biopsies for a histological diagnosis and the early diagnosis of anastomotic recurrences. EUS is indicated mainly for evaluating T stage before and after chemotherapy or chemoradiotherapy. CT-PET is extremely useful in identifying small mediastinal metastatic lymph nodes (N1) or extrathoracic lymph nodes (M1) and hepatic metastases (

Endoscopic treatment of pseudosarcomatous squamous carcinoma of the esophagus: case report and personal experience.

Spindle cell (or pseudosarcomatous) squamous carcinoma (PSC) is a rare malignant neoplasm of the esophagus, potentially capable of causing lymph node and distant metastases. Indications for surgery are the same as for squamous cell carcinoma (SCC) of the esophagus. The aims of this paper were to report a case of endoscopically treated PSC and to review our experience of surgically-treated patients with PSC in order to identify patients potentially suitable for endoscopic treatment. In our series of 4,460 patients with carcinoma of the esophagus observed between 1980 and 2003, 28 (0.6%) had the histological features of PSC. One had a PSC histologically confirmed (8cm-long polyp with a 3cm-large base) and endoscopically treated for high surgical risk. The patient had a close follow-up with endoscopic biopsies and ultrasonography with no local recurrence at 3 years. The overall survival rate was 22% for PSC and 17% for SCC (P = n.s.); after 5 years, the survival rates were 22% and 13%, respectively (P = n.s.). In our opinion the limited tendency to parietal infiltration and the good chance of disclosure in an early stage with endoscopic ultrasonography, justify non-surgical solutions in patients with a high surgical risk, possibly associated with adjuvant chemo- and radiotherapy since lymph node involvement is reported in 50% of cases. The limited number of patients with PSC involved in the present series prevent any significant statistical comparisons between the different groups, but the survival rates were roughly the same in the nonsurgical curative therapy as in the curative resection group, while the chances of survival were significantly lower in patients given palliative surgery and or non-curative treatments (P < 0.05).

The laparoscopic Heller-Dor operation remains an effective treatment for esophageal achalasia at a minimum 6-year follow-up.

BACKGROUND: The aim of this study was to investigate the long-term clinical outcome of the laparoscopic Heller Dor procedure for esophageal achalasia. METHODS: A total of 71 consecutive patients with a minimum 6 year follow-up were evaluated. These patients were seen at 1 and 6 months after the operation (at which time barium swallow, endoscopy, manometry, and pH monitoring were performed), and annually thereafter. A dedicated symptom score, that combined severity and frequency of symptoms was used. RESULTS: The median symptom score decreased from 22 (range, 9-29) preoperatively to 4 (range, 0-16) at last follow-up, (p < 0.01). During the follow-up period, 13 patients suffered symptom recurrence; seven of them (54%) had already been diagnosed at the 1-year follow-up. All of these patients were treated with complementary pneumatic dilations. Overall, at a minimum of 6- years after the operation, 81.7% of the patients were satisfied with the treatment and were able to eat normally. CONCLUSIONS: The long-term outcome of laparoscopic surgical treatment of esophageal achalasia is only slightly affected by the length of the follow-up and most of the symptomatic failures occur in the early period after the operation.

Botulinum toxin injection versus laparoscopic myotomy for the treatment of esophageal achalasia: economic analysis of a randomized trial.

BACKGROUND: The treatment of esophageal achalasia is still controversial: current therapies are palliative and aim to relieve dysphagia by disrupting or relaxing the lower esophageal sphincter muscle fibers with botulinum toxin. The aim of this study was to compare the clinical and economic results of two such treatments: laparoscopic myotomy and botulinum toxin injection. METHODS: A total of 37 patients with esophageal achalasia were randomly assigned to receive laparoscopic myotomy (20) or two Botox injections 1 month apart (17). All patients were treated at the same hospital and were part of a larger multicenter study. Symptom score, lower esophageal sphincter pressure, and esophageal diameter at barium swallow were compared. The economic analysis was performed considering only the direct costs (cost per treatment and cost effectiveness, i.e., cost per patient healed). RESULTS: Mortality and morbidity were nil in both groups. The actuarial probability of being asymptomatic at 2 years was 90% for surgery and 34% for Botox (p < 0.05). The initial cost was lower for Botox (1,245 Euros) than for surgery (3,555 Euros), but when cost effectiveness at 2 years was considered, this difference nearly disappeared: Botox 3,364 Euros, surgery 3,950 Euros. CONCLUSION: Botox is still the least costly treatment, but the minimal difference in the longer term does not justify its use, given that surgery is a risk-free, definitive treatment.

Role of acid and bile reflux in development of specialised intestinal metaplasia in distal oesophagus.

BACKGROUND: Barrett's oesophagus is defined as specialised intestinal metaplasia in the distal oesophagus, regardless of extension. AIM: To study distal oesophagus function, and acid and bile exposure in patients with Long Segment (>3 cm), Short Segment (1 to 2 cm) and Ultra-short Segment (<1 cm) Barrett's Oesophagus, and in patients with gastro-oesophageal reflux disease without intestinal metaplasia. PATIENTS: Study population comprised 17 patients with Long, 8 with Short, 9 with Ultra-Short Segment Barrett's oesophagus, 32 with reflux disease and 12 healthy volunteers. METHODS: Patients were evaluated by manometry and by 24-hour pH and bile monitoring. RESULTS: Patients with intestinal metaplasia had greater acid exposure of the distal oesophagus than healthy volunteers. Patients with Long Segment Barrett's oesophagus had a longer history of symptoms, worse lower oesophageal sphincter pressures and longer bile and acid exposure than the other patients. Long Segment Barrett's oesophagus was predicted by low oesophageal pressure and increased bile exposure, age and male sex. CONCLUSION: Acid exposure in the distal oesophagus is probably the aetiological factor behind intestinal metaplasia, but a severely damaged antireflux barrier and bile in the refluxate are necessary for Long Segment Barrett's Oesophagus to develop.

Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone.

BACKGROUND: Surgery is the standard treatment for patients with resectable esophageal carcinoma, but the long term prognosis of these patients is unsatisfactory. Some randomized trials of preoperative chemotherapy suggest that the prognosis of patients who respond may be improved. METHODS: This randomized, controlled trial compared patients with clinically resectable esophageal epidermoid carcinoma who underwent surgery alone (Arm A) with those who received preoperative chemotherapy (Arm B). Overall survival and the prognostic impact of major response to chemotherapy were analyzed. Forty-eight patients were enrolled in each arm. Chemotherapy consisted of two or three cycles of cisplatin (100 mg/m2 on Day 1) and 5- fluorouracil (1000 mg/m2 per day continuous infusion on Days 1-5). In both study arms, transthoracic esophagectomy plus two-field lymphadenectomy was performed. The two groups were comparable in terms of patient characteristics. RESULTS: Forty-seven patients were evaluable in each arm. The curative resection rate was 74.4% (35 of 47 patients) in Arm A and 78.7% (37 of 47 patients) in Arm B. Treatment-related mortality was 4.2% in both arms. The response rate to preoperative chemotherapy was 40% (19 of 47 patients), including 6 patients (12.8%) who achieved a pathologic complete responses. Overall survival was not improved significantly. The 19 patients in Arm B who responded to chemotherapy and underwent curative resection had significantly better 3-year and 5-year survival rates (74% and 60%, respectively) compared with both nonresponders (24% and 12%, respectively; P = 0.0002) and patients in Arm A who underwent complete resection (46% and 26%, respectively; P = 0.01): Patients who achieved a pathologic complete response (P = 0.01), but not those who achieved a partial response (P = 0.2), had significantly improved survival. CONCLUSIONS: Patients with resectable esophageal carcinoma who underwent preoperative chemotherapy and obtained a pathologic complete response had a significantly improved long term survival. Major efforts should be undertaken to identify patients before neoadjuvant treatments who are likely to respond.

MAGE, BAGE, and GAGE gene expression in patients with esophageal squamous cell carcinoma and adenocarcinoma of the gastric cardia.

BACKGROUND: The MAGE, BAGE, and GAGE gene families code for distinct, tumor specific antigens that are recognized by cytotoxic T lymphocytes in the context of HLA molecules. The purpose of this study was to analyze MAGE, BAGE, and GAGE gene expression in the two major histologic types of esophageal carcinoma, squamous carcinoma (ESCc) and adenocarcinoma (CAc), and to correlate their expression patterns with the principal prognostic parameters and long term survival. METHODS: Gene expression was analyzed in surgical samples from 24 patients with ESCc and 24 patients with CAc by reverse transcriptase-polymerase chain reaction amplification (RT-PCR). None of the patients had received preoperative chemotherapy or radiotherapy, and all were followed until death or for a minimum of 4 years. RESULTS: Sixteen ESCc samples (67%) and 9 CAc samples (37.5%) expressed at least one of the genes under study. The expression of each MAGE gene in the two histologic types was not significantly different, with the exception of MAGE-4, which was expressed more in ESCc samples than in CAc samples. BAGE and GAGE expression was rather low and, in every case, was associated with the expression of at least one MAGE gene. CONCLUSIONS: In the group as a whole, and in both ESCc and CAc subgroups, no significant correlation emerged between the expression of any gene and prognostic parameters, such as pathologic tumor, lymph node, or disease stage. Nevertheless, BAGE or GAGE expression was related significantly to a poor prognosis, whereas the expression of MAGE genes (in the absence of BAGE and GAGE expression) was related significantly to a good prognosis.

Oesophageal resection for high-grade dysplasia in Barrett's oesophagus.

BACKGROUND: The aims of this study were to evaluate the prevalence of invasive cancer in patients with high-grade dysplasia in Barrett's oesophagus and to verify whether a second endoscopy with multiple biopsies could improve the accuracy of preoperative diagnosis. In addition, the mortality, morbidity and survival rates in patients with high-grade dysplasia having oesophageal resection were recorded. METHODS: Fifteen patients were observed from 1982 to 1998; the first seven patients were offered primary oesophageal resection after diagnosis. The other eight patients underwent a second endoscopy with a median of 12 biopsies examined. All later underwent oesophageal resection. RESULTS: Invasive adenocarcinoma was found in five patients, with a minimal difference between the first and second periods (two of seven versus three of eight). There were no perioperative deaths. Early morbidity was observed in eight patients and late morbidity in four. The actuarial survival rate was 79 per cent at 5 years. The Karnofsky status was unchanged from preoperative values in 13 of 15 patients after a median follow-up of 46 months. CONCLUSION: These patients with high-grade dysplasia had a 33 per cent probability of harbouring invasive oesophageal carcinoma but even a second endoscopy failed to identify patients with invasive tumour. Oesophagectomy was performed with no deaths and remains a rational treatment in patients fit for surgery.

Anastomotic stenoses occurring after circular stapling in esophageal cancer surgery.

BACKGROUND: Circular staplers have reduced the incidence of anastomotic leaks in esophagovisceral anastomosis. However, the prevalence of stenosis is greater with staplers than with manual suturing. The aim of this study was to analyze potential risk factors for the onset of anastomotic stenoses and to evaluate their treatment and final outcome. METHODS: Between 1990 and 1995, 187 patients underwent esophagectomy and esophagogastrostomy with anastomosis performed inside the chest using a circular stapler. RESULTS: Twenty-three patients (12.3%) developed an anastomotic stenosis. The incidence of strictures was inversely related to the diameter of the stapler. Concomitant cardiovascular diseases; morphofunctional disorders of the tubulized stomach, such as those related to duodenogastric reflux; and neoadjuvant chemotherapy were also recognized as significant risk factors. Endoscopic dilatations proved safe and were effective in the treatment of most anastomotic stenoses. CONCLUSIONS: To reduce the risk of anastomotic stenosis after stapled intrathoracic esophagogastrostomy, adequate vascularization of the viscera being anastomized should be maintained, and it is mandatory to use the largest circular stapler suitable. Furthermore, it is essential to reduce the negative inflammation-inducing effects of duodenogastroesophageal reflux to a minimum. Endoscopic dilatations are safe and effective in curing the great majority of anastomotic stenoses.

Intestinal metaplasia is the probable common precursor of adenocarcinoma in barrett esophagus and adenocarcinoma of the gastric cardia.

BACKGROUND: Intestinal metaplasia in the tubular esophagus is the recognized precancerous lesion of adenocarcinoma in Barrett esophagus. However, it is not yet clear whether adenocarcinoma of the gastric cardia arises from the same premalignant lesion, i.e., intestinal metaplasia of the gastric cardia. The purpose of this study was to compare adenocarcinomas in Barrett esophagus and adenocarcinomas of the gastric cardia at an early stage, when it was more likely that intestinal metaplasia had not been completely overgrown by the tumor. METHODS: The authors compared the epidemiologic, clinical, and pathologic features of early stage adenocarcinoma in Barrett esophagus and adenocarcinoma of the gastric cardia from 42 patients who underwent resection surgery. The presence of intestinal metaplasia was assessed in the resected specimens by using Alcian blue (pH 2.5) staining. RESULTS: Intestinal metaplasia was detected in the mucosa adjacent to neoplasia in 25 of 26 patients with adenocarcinoma in Barrett esophagus and in 11 of 16 (69%) patients with adenocarcinoma of the gastric cardia. Patient and tumor characteristics and survival were comparable in both groups. CONCLUSIONS: Intestinal metaplasia is a very common finding in the mucosa adjacent to early stage adenocarcinoma of the gastric cardia. Adenocarcinoma in Barrett esophagus and adenocarcinoma of the gastric cardia may represent the same disease; the former arises from longer segments of intestinal metaplasia and the latter from intestinal metaplasia of the cardia.

Role of macronutrients, vitamins and minerals in the aetiology of squamous-cell carcinoma of the oesophagus.

Between 1992 and 1997 we conducted a case-control study of oesophageal cancer in 3 areas of northern Italy. Cases were 304 patients (29 women), ages 39-77 years (median age 60 years), with a first incident squamous-cell carcinoma (SCC) of the oesophagus. Controls were 743 patients (150 women), ages 35-77 years (median age 60 years), admitted for acute illnesses, unrelated to tobacco and alcohol, to major hospitals of the areas under surveillance. We derived estimates of daily dietary intake of 6 macronutrients, cholesterol, and 20 micronutrients or minerals from a validated food-frequency questionnaire, including 78 food groups and recipes and 15 questions on individual eating patterns. After allowance for age, gender, area of residence, education, body mass index, physical activity, smoking habit, alcohol consumption and energy intake, most micronutrients were inversely associated with oesophageal SCC risk. Highly significant associations emerged for monounsaturated fatty acids [odds ratio (OR) in highest vs. lowest intake quintile = 0.5]; carotene (OR = 0.3); lutein + zeaxanthin (OR = 0.4); vitamin C (OR = 0.4); and niacin (OR = 0.5). Only retinol appeared to be positively related to risk (OR = 1.9). The effect of the above nutrients, expressed as ORs, appeared to be similar in non-smokers and smokers, and non/light drinkers and heavy drinkers.

Anomalous transcripts and allelic deletions of the FHIT gene in human esophageal cancer.

The fragile histidine triad (FHIT) gene is localized on chromosome 3p14 and spans the common fragile site FRA3B. Even though its role in carcinogenesis is still unclear, this gene is frequently inactivated by carcinogen-induced intragenic deletions in many types of cancers, and FHIT abnormal transcripts are found in many primary tumors and tumor-derived cell lines. We evaluated FHIT gene involvement in 39 esophageal carcinomas (18 adenocarcinomas [AC¿, 21 squamous cell carcinomas [SCC]) by both reverse transcriptase-polymerase chain reaction (RT-PCR) amplification and loss of heterozygosity analysis (LOH). Thirty cases (77%) displayed either aberrant FHIT transcripts (12 cases) and/or LOH (24 cases); among these, only 6 samples displayed both aberrant transcripts and LOH, thus suggesting that the two events are probably independent. Moreover, LOH was significantly higher in SCC (80%) than in AC (44%), and because most of our patients are heavy smokers and/or alcohol consumers, these results suggest that the FHIT gene might be a common target for carcinogens also in the esophagus.

Chylothorax complicating esophagectomy for cancer: a plea for early thoracic duct ligation.

OBJECTIVE: Postoperative chylothorax remains an uncommon but potentially life-threatening complication of esophagectomy for cancer, and the ideal management is still controversial. The aim of the study was to compare the outcomes of patients treated nonoperatively with those of patients promptly undergoing reoperation. METHODS: From 1980 to 1998, 1787 esophagectomies for esophageal or cardia cancer were performed, and 19 (1.1%) patients had postoperative chylothorax. We analyzed type of operation, surgical approach, delay of diagnosis of chylothorax, daily chest tube output, type of management, major complications, death, hospital stay, and final outcome. RESULTS: Of the 19 patients with chylothorax, 11 were initially managed nonoperatively (group A): 4 (36%) patients had spontaneous resolution of chylothorax, and the other 7 required reoperation for the persistence of a high-volume output. There were three infectious complications and one postoperative death in this group. No reliable predictive criteria of successful versus unsuccessful nonoperative management could be found. The 8 most recent patients underwent early reoperation (group B). All patients recovered, and no major complications possibly related to chylothorax or hospital deaths were observed. They were discharged after a median of 22 days (range, 12-85 days) compared with a median of 36 days (range, 21-64 days) for patients of group A. CONCLUSIONS: Early thoracic duct ligation is the treatment of choice for chylothorax occurring after esophagectomy. Reoperation should be performed immediately after the diagnosis is made to avoid the complications related to nutritional and immunologic depletion caused by prolonged nonoperative treatment.

Esophageal cancer: a European perspective.

A survey was conducted among a group of European surgeons in order to investigate current attitudes and strategies in the management of squamous cell carcinoma of the esophagus. The survey consisted of a questionnaire mailed to surgeons in eight different countries with extensive clinical experience and scientific interest in the field. Eight questionnaires including the data of 6146 operated patients were available for analysis. A consensus emerged among the panelists that protocols of induction therapy should be routinely used in patients with locally advanced disease, especially in supracarinal tumors. Four of the surgeons advocated bilateral neck dissection in these patients. A progressive improvement in survival over the past three decades was noted. After 1990, the postoperative mortality rate was 6.2% after surgery alone and 9.7% after chemoradiation therapy followed by surgery. The 5-year survival rate after a complete resection was 38.5%. In the opinion of the panelists, esophagectomy remains the "gold standard" of therapy and should be regarded as an integral component of the treatment plan for patients with squamous cell carcinoma.