Complete clinical response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic oesophagus: is surgery always necessary?

BACKGROUND: Neoadjuvant chemoradiotherapy (CT-RT) before oesophagectomy is standard management for squamous cell carcinoma(SCC) of the thoracic oesophagus. The aim of this study was to compare the outcome of patients who had clinical complete response(CR) with neoadjuvant CT-RT + oesophagectomy with the survival of patients who had clinical CR and were not operated on. PATIENTS AND METHODS: Seventy-seven consecutive patients with SCC of the thoracic oesophagus with CR with neoadjuvant CT-RT presenting at the Regional Center of Esophageal Diseases from 1992 to 2008 were included in this retrospective study on a prospectively collected database. Thirty-nine patients underwent oesophagectomy (CT-RT + oesophagectomy), while 38(CT-RT) were not operated on because they were considered unfit for surgery or refused the operation. Patients' outcome and survival were compared. RESULTS: In the CT-RT + oesophagectomy group, clinical CR was confirmed after histological examination of the surgical specimen in 27/39 (69.2 %) patients. Five-year overall survival rates were 50.0 % in the CT-RT + oesophagectomy group and 57.0 % in the CT-RT group (p=0.99); 5-year disease-free survival rates were 55.5%in the CT-RT + oesophagectomy group and 34.6%in the CTRT group (p=0.15). Even after adjusting for propensity score, age, ASA and clinical stage, the treatment regimen did not show a statistically significant effect on overall survival (adjusted p=0.65) nor on disease-free survival (adjusted p=0.15). CONCLUSION: In our group of patients with clinical CR after neoadjuvant CT-RT for SCC of the thoracic oesophagus, waiting for recurrence and then using salvage surgery did not negatively impact their survival compared to patients treated with surgery. More accurate restaging protocols are warranted to improve decision making after CR with neoadjuvant CT-RT.

Nodal metastasis from locally advanced esophageal cancer: how neoadjuvant therapy modifies their frequency and distribution.

BACKGROUND: Neoadjuvant chemoradiotherapy (CT-RT) before esophagectomy seems to affect the number of nodal metastasis and to alter the distribution of those that remain. The aim of this study was to define how neoadjuvant chemoradiotherapy changes nodal metastasis patterns in locally advanced esophageal cancer. METHODS: A total of 402 consecutive patients with cancer of the esophagus or esophagogastric junction (181 adenocarcinoma [AC] and 221 squamous cell carcinoma [SCC]) (evaluated at clinical stage T1N1, T2N1, T3N0, or T3N1 and pathological stage M0) presenting in our Department between 1992 and 2007 and who underwent complete resection (R0) were included in this retrospective study on a prospectively collected database. All dissected lymph nodes were retrieved and microscopically analyzed. Nodal metastasis patterns in patients who underwent chemotherapy (CT) or chemoradiotherapy (CT-RT) neoadjuvant therapy were compared with those in patients who underwent surgery alone. RESULTS: Almost 30% of the adenocarcinoma patients and approximately 40% of the SCC patients showed effective tumor downstaging after neoadjuvant therapy. There were fewer paracardial node metastases (P = .002) in the AC patients who underwent CT-RT neoadjuvant therapy. There were, likewise, significantly fewer paraesophageal, paracardial, and subcarinal node metastases in the SCC patients in whom the perigastric nodes became the second-most frequent site of metastasis. CONCLUSION: Not only was frequency of lymph node metastases decreased after neoadjuvant therapy, but nodal localization and pattern were also significantly modified.

Effects of long-term administration of high-dose recombinant human antithrombin in immunosuppressed primate recipients of porcine xenografts.

BACKGROUND: Fibrin deposition is central to the acute humoral rejection process occurring in the presence of consumptive coagulopathy when pig organs are transplanted into primates. METHODS: To assess whether strategies aimed at preventing fibrin formation may extend xenograft survival, we administered high daily doses of recombinant human antithrombin (rhAT) (500 U/kg twice daily) to obtain both anticoagulant and anti-inflammatory effects in immunosuppressed primate recipients of porcine kidneys. RESULTS: Some degree of consumptive coagulopathy developed in both rhAT-treated (n=3) and untreated (n=3) primates. No major differences in the coagulation parameters analyzed were observed between the 2 groups. Similarly, no difference in survival was seen between rhAT-treated (20.6+/-4 days; range: 15-23 days) and untreated animals (17.3+/-11.6 days; range: 7-30 days), although the rhAT-treated primates had a higher bleeding tendency. Despite the high daily dose of rhAT, considerable fibrin deposition was observed in the graft as early as 2 weeks after transplantation. CONCLUSIONS: These results suggest that a high daily dose of rhAT fails to influence survival or prevent fibrin formation and deposition in the graft in our pig-to-primate model. However, the potential role of rhAT administered in combination with heparins or other clotting inhibitor concentrates in this model remains to be determined.