Background Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. Methods Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. Results Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P Ͻ 0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses, as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P ϭ 0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P ϭ 0.01). Conclusions Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.
Chylothorax is an uncommon complication of oesophagectomy. In a review of 537 oesophageal resections there were 11 cases of chylothorax, an incidence of 2.0 per cent. There was no correlation with site, size, penetration, lymph node status, length or type of tumour but there was a significant correlation between chylothorax and the type of operative procedure carried out. The incidence in 95 transhiatal resections was 10.5 per cent. The incidence following 442 transthoracic procedures was 0.2 per cent (P less than 0.001) with one chylous fistula occurring after a three-stage oesophagectomy. Initial management was conservative with chest drainage and total parenteral nutrition. Thoracotomy and duct ligation was subsequently carried out in three patients and was successful in two. The third patient died. Conservative management alone was successful in four out of eight patients, with closure of the fistula at a median of 35 days (range 14-42 days). Four patients treated conservatively died. Transhiatal oesophagectomy greatly increases the risk of chylothorax, a condition that carries a high mortality rate (46 per cent in this series) whether managed conservatively or by surgical intervention.
Endoscopic transthoracic electrocautery of the sympathetic chain has been the preferred treatment for palmar or axillary hyperhidrosis in this unit since 1980. A retrospective study was carried out of the first 112 patients with case material derived from a postal questionnaire, chart review and outpatient assessment. Eighty-five patients undergoing bilateral transthoracic electrocautery who replied to the questionnaire (76 per cent response rate) form the basis of this study. There were 65 females and 20 males with a mean age of 24.3 years (range 15-40 years). The hands alone were affected in 20 patients (24 per cent), the axillae alone in 17 (20 per cent) and both areas in 48 (56 per cent). Mean hospital stay was 3.1 days (range 1-7 days). Outcome was assessed by 92 per cent of patients immediately after operation as 'very much improved' or 'moderately improved', and this assessment persisted in 85 per cent after a mean follow-up of 43 months (range 3-95 months). Cosmetic results were rated as satisfactory by 95 per cent. Apart from pain after operation, morbidity was limited to transient Horner's syndrome in three patients, surgical emphysema in three, and pneumothorax requiring a chest drain in one. A repeat procedure was needed in one patient because of an inadequate first operation. Some compensatory hyperhidrosis occurred in 54 (64 per cent) patients. As a minimally invasive procedure, endoscopic transthoracic electrocautery should be considered the treatment of choice for palmar and axillary hyperhidrosis.
Background. Multimodality therapy with chemotherapy and radiotherapy followed by surgery may improve survival in patients with esophageal squamous cell carcinoma compared with each of the individual treatment options. Histologic assessment of resected tumors after chemoradiotherapy shows that some patients have a complete response with no residual tumor, whereas other patients derive no benefit. The ability to predict response to chemoradiotherapy would allow treatment to be planned accordingly. Methods. Expression of the tumor growth and proliferation proteins epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) was determined using immunohistochemical staining of pretreatment endoscopic biopsies from patients with esophageal squamous cell carcinoma who were randomized to chemoradiotherapy before surgery. Response to chemoradiotherapy was assessed by histologic examination of the resected specimens. Response to chemoradiotherapy and survival were correlated with EGFR and PCNA expression individually and with both markers combined as EGFR/PCNA. Results. Of 14 patients available for study, 6 had a complete histologic response (CR) to chemoradiotherapy with no residual tumor in the resected specimen, 3 had a partial response (PR) to chemoradiotherapy, and the remaining 5 had minimal response (MR). Of the nine patients with a CR or PR, tumors of eight patients were negative for one or both markers. Of the five patients with an MR, four tumors were positive for both EGFR and PCNA (P < 0.05, Fisher's exact test). Comparison of survival from the date of randomization shows that patients with tumors negative for one or both markers had a signiticant survival advantage (P = 0.0003, log‐rank test). Conclusions. Evaluation of PCNA and EGFR status of pretreatment biopsies may identify a group of patients likely to derive the greatest benefit from chemoradiotherapy before surgery in terms of histologic response and long term survival.
Bile reflux has been implicated in the pathogenesis of Barrett's oesophagus but evaluation remains difficult. Bilitec 2000 is an ambulatory system that detects bilirubin based on its spectrophotometric properties. Oesophageal bile exposure was evaluated in three groups of patients. Group 1 (n = 11) were normal controls, group 2 (n = 13) were patients with uncomplicated gastro-oesophageal reflux and group 3 (n = 12) were patients with Barrett's oesophagus. Bile reflux was greater in patients with Barrett's mucosa than in controls or those with uncomplicated reflux. This difference was seen in the supine and interdigestive periods. The percentage of time at which gastric pH was greater than 4 and oesophageal pH was above 7 did not differ between the groups. Bilitec 2000 detects greater bile reflux in patients with Barrett's oesophagus. No corresponding gastric or oesophageal alkaline shift is found. This ambulatory bile reflux monitoring system may be a useful tool in clinical practice.
Background An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. Methods The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. Discussion The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. Trial registration NCT03222895 , date of registration: July 19th, 2017.
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