Background Controversy exists about the best surgical treatment for esophageal carcinoma. Methods We randomly assigned 220 patients with adenocarcinoma of the mid-to-distal esophagus or adenocarcinoma of the gastric cardia involving the distal esophagus either to transhiatal esophagectomy or to transthoracic esophagectomy with extended en bloc lymphadenectomy. Principal end points were overall survival and disease-free survival. Early morbidity and mortality, the number of quality-adjusted life-years gained, and cost effectiveness were also determined. Results A total of 106 patients were assigned to undergo transhiatal esophagectomy, and 114 to undergo transthoracic esophagectomy. Demographic characteristics and characteristics of the tumor were similar in the two groups. Perioperative morbidity was higher after transthoracic esophagectomy, but there was no significant difference in in-hospital mortality (P=0.45). After a median follow-up of 4.7 years, 142 patients had died — 74 (70 percent) after transh...

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Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus.

Summary Background In a previous meta-analysis, we identified a survival benefit from neoadjuvant chemotherapy or chemoradiotherapy before surgery in patients with resectable oesophageal carcinoma. We updated this meta-analysis with results from new or updated randomised trials presented in the past 3 years. We also compared the benefits of preoperative neoadjuvant chemotherapy compared with neoadjuvant chemoradiotherapy. Methods To identify additional studies and published abstracts from major scientific meetings, we searched Medline, Embase, and Central (Cochrane clinical trials database) for studies published since January, 2006, and also manually searched for abstracts from major conferences from the same period. Only randomised studies analysed by intention to treat were included, and searches were restricted to those databases citing articles in English. We used published hazard ratios (HRs) if available or estimates from other survival data. We also investigated treatment effects by tumour histology and relations between risk (survival after surgery alone) and effect size. Findings We included all 17 trials from the previous meta-analysis and seven further studies. 12 were randomised comparisons of neoadjuvant chemoradiotherapy versus surgery alone (n=1854), nine were randomised comparisons of neoadjuvant chemotherapy versus surgery alone (n=1981), and two compared neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy (n=194) in patients with resectable oesophageal carcinoma; one factorial trial included two comparisons and was included in analyses of both neoadjuvant chemoradiotherapy (n=78) and neoadjuvant chemotherapy (n=81). The updated analysis contained 4188 patients whereas the previous publication included 2933 patients. This updated meta-analysis contains about 3500 events compared with about 2230 in the previous meta-analysis (estimated 57% increase). The HR for all-cause mortality for neoadjuvant chemoradiotherapy was 0·78 (95% CI 0·70–0·88; p Interpretation This updated meta-analysis provides strong evidence for a survival benefit of neoadjuvant chemoradiotherapy or chemotherapy over surgery alone in patients with oesophageal carcinoma. A clear advantage of neoadjuvant chemoradiotherapy over neoadjuvant chemotherapy has not been established. These results should help inform decisions about patient management and design of future trials. Funding Cancer Australia and the NSW Cancer Institute.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(11)70142-5.pdf

Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis

Background We conducted a multicenter, randomized trial to compare preoperative chemoradiotherapy followed by surgery with surgery alone in patients with stage I and II squamous-cell cancer of the esophagus. Methods The preoperative combined therapy consisted of two one-week courses; each involved radiotherapy, in a dose of 18.5 Gy delivered in five fractions of 3.7 Gy each, and 80 mg of cisplatin per square meter of body-surface area, administered 0 to 2 days before the first day of radiotherapy. The surgical plan included one-stage en bloc esophagectomy and proximal gastrectomy by the abdominal and right thoracic routes, to be performed immediately after randomization in the group assigned to surgery alone and two to four weeks after the completion of preoperative chemoradiotherapy in the group assigned to combined therapy. Results A total of 297 patients entered the study; 11 were found to be ineligible, and 4 were lost to follow-up. Of the remaining 282, 139 were assigned to surgery alone and 143 to c...

https://www.nejm.org/doi/pdf/10.1056/NEJM199707173370304

Chemoradiotherapy Followed by Surgery Compared with Surgery Alone in Squamous-Cell Cancer of the Esophagus

Summary Background Resection remains the best treatment for carcinoma of the oesophagus in terms of local control, but local recurrence and distant metastasis remain an issue after surgery. We aimed to assess whether a short preoperative chemoradiotherapy regimen improves outcomes for patients with resectable oesophageal cancer. Methods 128 patients were randomly assigned to surgery alone and 128 patients to surgery after 80 mg/m 2 cisplatin on day 1, 800 mg/m 2 fluorouracil on days 1–4, with concurrent radiotherapy of 35 Gy given in 15 fractions. The primary endpoint was progression-free survival. Secondary endpoints were overall survival, tumour response, toxic effects, patterns of failure, and quality of life. Analysis was done by intention to treat. Findings Neither progression-free survival nor overall survival differed between groups (hazard ratio [HR] 0·82 [95% CI 0·61–1·10] and 0·89 [0·67–1·19], respectively). The chemoradiotherapy-and-surgery group had more complete resections with clear margins than did the surgery-alone group (103 of 128 [80%] vs 76 of 128 [59%], p=0·0002), and had fewer positive lymph nodes (44 of 103 [43%] vs 69 of 103 [67%], p=0·003). Subgroup analysis showed that patients with squamous-cell tumours had better progression-free survival with chemoradiotherapy than did those with non-squamous tumours (HR 0·47 [0·25–0·86] vs 1·02 [0·72–1·44]). However, the trial was underpowered to determine the real magnitude of benefit in this subgroup. Interpretation Preoperative chemoradiotherapy with cisplatin and fluorouracil does not significantly improve progression-free or overall survival for patients with resectable oesophageal cancer compared with surgery alone. However, further assessment is warranted of the role of chemoradiotherapy in patients with squamous-cell tumours.

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Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial.

Background Esophagectomy is a standard treatment for resectable esophageal cancer but relatively few patients are cured. Combining neoadjuvant chemoradiation with surgery may improve survival but treatment morbidity is a concern. We performed a meta-analysis of randomized controlled trials (RCTs) that compared the use of neoadjuvant chemoradiation and surgery with the use of surgery alone for esophageal cancer. Methods Medline and manual searches were done to identify all published RCTs that compared neoadjuvant chemoradiation and surgery with surgery alone for esophageal cancer. A random-effects model was used and the odds ratio (OR) was the principal measure of effect. Systematic quantitative review was done for outcomes unique to the neoadjuvant chemoradiation treatment group, such as pathological complete response. Results Nine RCTs that included 1,116 patients were selected with quality scores ranging from 1 to 3 (5-point Jadad scale). Odds ratio (95% confidence interval [CI]; P value), expressed as chemoradiation and surgery versus surgery alone (treatment versus control; values Conclusions Compared with surgery alone, neoadjuvant chemoradiation and surgery improved 3-year survival and reduced local-regional cancer recurrence. It was associated with a lower rate of esophageal resection, but a higher rate of complete (R0) resection. There was a nonsignificant trend toward increased treatment mortality with neoadjuvant chemoradiation. Concurrent administration of neoadjuvant chemotherapy and radiotherapy was superior to sequential chemoradiation treatment scheduling.

A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer

During the past 10 years, postoperative mortality associated with surgical treatment of oesophageal carcinoma has been reduced by one-half. However, it appears that all efforts to improve long-term survival with extensive excisional procedures and adjuvant chemotherapy and radiotherapy have failed. Fifty-six of 100 patients presenting to the surgeon with an oesophageal carcinoma have resectable disease. Recent studies suggest that seven of them will die from postoperative complications and 49 patients will be discharged from the hospital after an average of 3 weeks. Of these patients, 27 will survive the first, 12 the second, and ten the fifth year. Although it may be possible to further reduce postoperative complications and mortality, the chances of improving the long-term prognosis of patients with oesophageal carcinoma seem small.

Surgical therapy of oesophageal carcinoma.

Postoperative radiation therapy following curative resection of squamous cell carcinoma of the esophagus was investigated in a prospective randomized study. A group of 33 patients received postoperative radiation therapy and were compared to a control group of 35 patients treated by surgery alone. No statistically significant differences were noted between the two treatment groups concerning overall and disease-free survival rates. Postoperative irradiation significantly increased the incidence of fibrotic strictures of the esophagogastric or esophagocolonic anastomoses and caused a delayed recovery of patients quality of life. Based on these results, we believe that postoperative radiation therapy alone cannot be advocated as a adjuvant therapy following curative resection of squamous cell carcinoma of the esophagus.

Adjuvant postoperative radiation therapy after curative resection of squamous cell carcinoma of the thoracic esophagus: A prospective randomized study

The expression of MUC1 and MUC2 mucin peptide core antigens in gastric carcinomas was studied by immunohistochemistry to determine correlations with TNM stage and histo-pathological classifications as well as a possible prognostic impact. Paraffin-embedded specimens from 128 gastric carcinomas with a minimal follow-up of 5 years were immunostained. In addition to a polyclonal antiserum generated against polymorphic epithelial mucin (MUC1) from human milk, 2 monoclonal antibodies (MAbs), HMFG2 (anti-MUC1) and 4FI (anti-MUC2), were applied. Reactivity of carcinomas was correlated with the classifications of the UICC (TNM), WHO and Lauren. Correlations with overall survival were analyzed using the Kaplan and Meier product limit method. MUC1 immunoreactivity was associated with an advanced pTNM stage. The demonstration of both mucin species (MUC1, MUC2) displayed a statistically significant correlation with tubular/papillary vs. signet-ring cell differentiation as well as with intestinal-type vs. diffuse-type of tumor growth according to Lauren. In particular, MUC2 was only rarely detectable in signet-ring cell and diffuse-type tumors. MUC1 correlated with poor prognosis in all cases and the subgroup of stage I tumors. According to the histopathological classifications, a similar result was observed in signet-ring cell and diffuse-type carcinomas. In contrast, MUC2 reactivity was associated with a favourable prognosis of intestinal-type carcinomas. In the non-neoplastic gastric mucosa, both peptide cores were recognized in the superficial epithelium, whereas parietal cells contained only MUC1, and intestinal metaplasia almost exclusively MUC2 antigens. We conclude that the mucin peptide core antigens are suitable markers for the tubule-rich gastric carcinomas, which may in part be derived from intestinal metaplasia. In addition, MUC1 may exert a prognostic relevance and appears to be involved in the progression of diffuse-type tumors.

Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas

The effect of total parenteral nutrition (TPN) as sole therapy was studied in 30 consecutive cases of complicated Crohn's disease. After insertion of a Broviac-type central venous catheter patients were nourished parenterally for 3 weeks in the hospital and then for an additional 9 weeks at home. During this time no medication or oral intake was allowed. Surgery was avoided in 25 patients by TPN. These patients returned to work, ate normal meals and needed no medical support. In 5 cases it was not possible to control the acute disease and the patients were treated by resection. During TPN, catheter-related sepsis occurred in 3 patients (0.9 cases/1000 days TPN) and catheter embolism in 2. Four other patients developed intrahepatic cholestasis. A relapse of Crohn's disease was observed in 17 cases 3-48 months after the course of TPN. The cumulative recurrence rate is 60 per cent after 2 years and 85 per cent after 4 years. Compared with the results of resection, obtained from a 10-year period before TPN was instituted at our hospital, the cumulative recurrence rate after TPN is four times higher. It is concluded that TPN is not an alternative to resection in the treatment of Crohn's disease and should be reserved for patients with multifocal lesions, when surgery is not advisable because of the risk of a short bowel syndrome.

Total parenteral nutrition as the sole therapy in Crohn's disease--a prospective study.

Three different methods of preoperative bowel preparation were tested in a prospective randomized trial examining efficacy and morbidity. In all, 163 patients were treated by gut irrigation with Ringer's lactate, Prepacol or polyethylene glycol (PEG). Fluid retention, cleansing effect, postoperative complications and subjective acceptance were documented. Relevant weight gain and decrease in haematocrit indicating fluid retention were seen only after the use of Ringer's lactate. There were no significant differences in bowel cleansing. In the Prepacol group the postoperative complication rate was significantly increased. Prepacol was tolerated best, with few side-effects. PEG was better tolerated than Ringer's lactate, but vomiting occurred in 2 and 21 per cent of patients respectively. PEG is most suitable for bowel preparation in patients undergoing colorectal surgery.

H. Pichlmaier

Papers

Surgical therapy of oesophageal carcinoma.

Adjuvant postoperative radiation therapy after curative resection of squamous cell carcinoma of the thoracic esophagus: A prospective randomized study

Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas

Total parenteral nutrition as the sole therapy in Crohn's disease--a prospective study.

Prospective randomized study of preoperative bowel cleansing for patients undergoing colorectal surgery.