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Systematic lymphadenectomy versus sampling of ipsilateral mediastinal lymph-nodes during lobectomy for non-small-cell lung cancer: a systematic review of randomized trials and a meta-analysis.

ABSTRACT: OBJECTIVES:To re-examine the evidence for recommendations for complete dissection versus sampling of ipsilateral mediastinal lymph nodes during lobectomy for cancer. METHODS:We searched for randomized trials of systematic mediastinal lymphadenectomy versus mediastinal sampling. We performed a textual analysis of the authors' own starting assumptions and conclusion. We analysed the trial designs and risk of bias. We extracted data on early mortality, perioperative complications, overall survival, local recurrence and distant recurrence for meta-analysis. RESULTS:We found five randomized controlled trials recruiting 1980 patients spanning 1989-2007. The expressed starting position in 3/5 studies was a conviction that systematic dissection was effective. Long-term survival was better with lymphadenectomy compared with sampling (Hazard Ratio 0.78; 95% CI 0.69-0.89) as was perioperative survival (Odds Ratio 0.59; 95% CI 0.25-1.36, non-significant). But there was an overall high risk of bias and a lack of intention to treat analysis. There were higher rates (non-significant) of perioperative complications including bleeding, chylothorax and recurrent nerve palsy with lymphadenectomy. CONCLUSIONS:The high risk of bias in these trials makes the overall conclusion insecure. The finding of clinically important surgically related morbidities but lower perioperative mortality with lymphadenectomy seems inconsistent. The multiple variables in patients, cancers and available treatments suggest that large pragmatic multicentre trials, testing currently available strategies, are the best way to find out which are more effective. The number of patients affected with lung cancer makes trials feasible.

SUBMITTER: Mokhles S

PROVIDER: S-EPMC6095012 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Systematic lymphadenectomy versus sampling of ipsilateral mediastinal lymph-nodes during lobectomy for non-small-cell lung cancer: a systematic review of randomized trials and a meta-analysis.

Mokhles Sahar S Macbeth Fergus F Treasure Tom T Younes Riad N RN Rintoul Robert C RC Fiorentino Francesca F Bogers Ad J J C AJJC Takkenberg Johanna J M JJM

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 20170601 6

<h4>Objectives</h4>To re-examine the evidence for recommendations for complete dissection versus sampling of ipsilateral mediastinal lymph nodes during lobectomy for cancer.<h4>Methods</h4>We searched for randomized trials of systematic mediastinal lymphadenectomy versus mediastinal sampling. We performed a textual analysis of the authors' own starting assumptions and conclusion. We analysed the trial designs and risk of bias. We extracted data on early mortality, perioperative complications, ov ...[more]

PMID: 28158453

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Project description:Pandemic live attenuated influenza vaccines (pLAIV) prime subjects for a robust neutralizing antibody response upon subsequent administration of a pandemic inactivated subunit vaccine (pISV). However, a difference was not detected in H5-specific memory B cells in the peripheral blood between pLAIV-primed and unprimed subjects prior to pISV boost. To investigate the mechanism underlying pLAIV priming, we vaccinated groups of 12 African green monkeys (AGMs) with H5N1 pISV or pLAIV alone or H5N1 pLAIV followed by pISV and examined immunity systemically and in local draining lymph nodes (LN). The AGM model recapitulated the serologic observations from clinical studies. Interestingly, H5N1 pLAIV induced robust germinal center B cell responses in the mediastinal LN (MLN). Subsequent boosting with H5N1 pISV drove increases in H5-specific B cells in the axillary LN, spleen, and circulation in H5N1 pLAIV-primed animals. Thus, H5N1 pLAIV primes localized B cell responses in the MLN that are recalled systemically following pISV boost. These data provide mechanistic insights for the generation of robust humoral responses via prime-boost vaccination.IMPORTANCE We have previously shown that pandemic live attenuated influenza vaccines (pLAIV) prime for a rapid and robust antibody response on subsequent administration of inactivated subunit vaccine (pISV). This is observed even in individuals who had undetectable antibody (Ab) responses following the initial vaccination. To define the mechanistic basis of pLAIV priming, we turned to a nonhuman primate model and performed a detailed analysis of B cell responses in systemic and local lymphoid tissues following prime-boost vaccination with pLAIV and pISV. We show that the nonhuman primate model recapitulates the serologic observations from clinical studies. Further, we found that pLAIVs induced robust germinal center B cell responses in the mediastinal lymph node. Subsequent boosting with pISV in pLAIV-primed animals resulted in detection of B cells in the axillary lymph nodes, spleen, and peripheral blood. We demonstrate that intranasally administered pLAIV elicits a highly localized germinal center B cell response in the mediastinal lymph node that is rapidly recalled following pISV boost into germinal center reactions at numerous distant immune sites.

Dataset Information

Systematic lymphadenectomy versus sampling of ipsilateral mediastinal lymph-nodes during lobectomy for non-small-cell lung cancer: a systematic review of randomized trials and a meta-analysis.

Publications

Systematic lymphadenectomy versus sampling of ipsilateral mediastinal lymph-nodes during lobectomy for non-small-cell lung cancer: a systematic review of randomized trials and a meta-analysis.

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