The optimal treatment of esophageal cancer is still being defined. The timing of surgical management and the application of chemotherapy and radiation in the neoadjuvant and adjuvant settings have been studied in several prospective, randomized, controlled trials. This article outlines some of the historical as well as updated research that has been published regarding the management of esophageal cancer.
Key points
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There is no difference in oncologic outcomes comparing transhiatal with transthoracic esophagectomy.
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Nasogastric tubes assist in decreasing perioperative complications.
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Preoperative chemotherapy trials are difficult to evaluate because studies have examined squamous cell carcinoma versus adenocarcinoma and inconsistently included gastroesophageal junction and gastric cardia tumors.
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Standard of care in Europe includes preoperative cisplatin and 5-fluoracil; however, ongoing studies are needed to study the subgroups of patients who benefit most from neoadjuvant chemotherapy.
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Randomized trials of preoperative radiation therapy have not increased resectability rates; a few recent trials show variable results in survival and pathologic complete responses with preoperative chemoradiotherapy.
Surgical management
The surgical approach to esophageal cancer involves either transhiatal or transthoracic esophagectomy. Hulscher and colleagues randomized 220 patients with middle or distal esophageal cancer to either transhiatal or transthoracic esophagectomy. Original results revealed no difference in R0 resection rates, although the lymph node retrieval was significantly higher in the transthoracic group (31 vs 16; P <.001). Postoperative pulmonary complications and hospital duration of stay were higher in patients who underwent transthoracic esophagectomy. However, there were no differences in the perioperative mortality rates. Additionally, there were no differences in local or distant recurrence rates. Five-year survival analysis was comparable (34% and 36%; P = .71). Three other phase III trials prospectively examined the outcomes of patients assigned to transhiatal and transthoracic esophagectomy, but no definitive conclusions could be reached owing to small sample sizes.
Various reconstructive techniques have been addressed by 3 prospective, randomized, controlled trials. Gupta and colleagues found a lower leak rate of 4.3% versus 20.8% ( P = .03) and stricture rate of 8.5% versus 29.2% ( P = .02) after a “novel” hand-sewn esophagogastric anastomosis compared with a standard hand-sewn anastomosis. Bhat and colleagues found the anastomotic leak rate to be dramatically reduced after omental wrap of the esophagogastric anastomosis versus standard anastomosis (3.09% vs 14.43%; P = .005). Tabira and colleagues found no difference in anastomotic leak or postoperative nutritional status at 6 and 12 months after use of a slender gastric tube for reconstruction after esophagectomy when compared with a more generous gastric tube. Nederlof and colleagues studied using an end-to-end (ETE) versus an end-to-side (ETS) esophagogastrostomy after esophageal cancer resection. This Dutch trial found the anastomotic stricture rate to be higher with the ETE anastomosis, but that the anastomotic leak rate, pulmonary complications, and duration of hospital stay were greater with an ETS anastomosis.
A number of trials addressed other surgical technique issues. A comparison of the Ivor-Lewis and Sweet esophagectomy techniques was performed for esophageal squamous cell carcinoma in 2015 by Li and colleagues Operative morbidity was higher with the Sweet technique, and Ivor-Lewis esophagectomy led to higher lymph node yield. A small institutional randomized trial also found that in prone versus decubitus positioning for minimally invasive esophagectomy, the prone positioning may decrease surgeon workload and lead to better ergonomic results. A multicenter, open-label, randomized, controlled trial by Biere and colleagues evaluated open esophagectomy versus minimally invasive esophagectomy. Short-term pulmonary complications were better with the minimally invasive technique, suggesting the usefulness of the minimally invasive approach over open esophagectomy in clinical practice and as an area for further research into long-term outcomes.
Surgical management
The surgical approach to esophageal cancer involves either transhiatal or transthoracic esophagectomy. Hulscher and colleagues randomized 220 patients with middle or distal esophageal cancer to either transhiatal or transthoracic esophagectomy. Original results revealed no difference in R0 resection rates, although the lymph node retrieval was significantly higher in the transthoracic group (31 vs 16; P <.001). Postoperative pulmonary complications and hospital duration of stay were higher in patients who underwent transthoracic esophagectomy. However, there were no differences in the perioperative mortality rates. Additionally, there were no differences in local or distant recurrence rates. Five-year survival analysis was comparable (34% and 36%; P = .71). Three other phase III trials prospectively examined the outcomes of patients assigned to transhiatal and transthoracic esophagectomy, but no definitive conclusions could be reached owing to small sample sizes.
Various reconstructive techniques have been addressed by 3 prospective, randomized, controlled trials. Gupta and colleagues found a lower leak rate of 4.3% versus 20.8% ( P = .03) and stricture rate of 8.5% versus 29.2% ( P = .02) after a “novel” hand-sewn esophagogastric anastomosis compared with a standard hand-sewn anastomosis. Bhat and colleagues found the anastomotic leak rate to be dramatically reduced after omental wrap of the esophagogastric anastomosis versus standard anastomosis (3.09% vs 14.43%; P = .005). Tabira and colleagues found no difference in anastomotic leak or postoperative nutritional status at 6 and 12 months after use of a slender gastric tube for reconstruction after esophagectomy when compared with a more generous gastric tube. Nederlof and colleagues studied using an end-to-end (ETE) versus an end-to-side (ETS) esophagogastrostomy after esophageal cancer resection. This Dutch trial found the anastomotic stricture rate to be higher with the ETE anastomosis, but that the anastomotic leak rate, pulmonary complications, and duration of hospital stay were greater with an ETS anastomosis.
A number of trials addressed other surgical technique issues. A comparison of the Ivor-Lewis and Sweet esophagectomy techniques was performed for esophageal squamous cell carcinoma in 2015 by Li and colleagues Operative morbidity was higher with the Sweet technique, and Ivor-Lewis esophagectomy led to higher lymph node yield. A small institutional randomized trial also found that in prone versus decubitus positioning for minimally invasive esophagectomy, the prone positioning may decrease surgeon workload and lead to better ergonomic results. A multicenter, open-label, randomized, controlled trial by Biere and colleagues evaluated open esophagectomy versus minimally invasive esophagectomy. Short-term pulmonary complications were better with the minimally invasive technique, suggesting the usefulness of the minimally invasive approach over open esophagectomy in clinical practice and as an area for further research into long-term outcomes.
Perioperative outcomes
Shackcloth and colleagues completed a well-planned and executed study addressing the most appropriate use of nasogastric tubes (NGT) in the first 48 hours after esophagectomy. Thirty-four patients were randomized to NGT with continuous sump suction, single-lumen NGT with 4-hourly aspirations, or no NGT. The patients receiving continuous suction via the sump system spent significantly less time with a pH of less than 5.5 than either of the other 2 groups (4.3% vs 39.7% vs 40.3% [ P = .007]). Patients randomized to no NGT had significantly more pulmonary complications, 7 of 12 versus 4 of 22 ( P = .02), and required an NGT to be inserted in 7 of 12 cases. This study argues for the use of sump NGT in patients in the immediate perioperative period. A follow-up study by Mistry and colleagues hypothesized that early removal of NGT would not adversely affect major pulmonary complications and anastomotic leak rates. This was confirmed in their single-center, parallel-group, open-label randomized trial of 150 patients.
Other recent trials have focused on perioperative interventions. The safety analysis of the Japan Clinical Oncology Group 9907 trial compared preoperative and postoperative chemotherapy in 330 patients and found that operative and postoperative complications were similarly low. Eicosapentaenoic acid (EPA)-enriched enteral nutrition (EN) was compared with standard EN and found to preserve fat-free mass better than standard nutrition and significantly attenuated stress response. Several studies have shown that ghrelin can improve postoperative outcomes and minimize adverse events, even during the time of chemotherapy. Synbiotics were similarly studied and found to decrease the inflammatory response after surgery. Shyamsundar and colleagues also looked at simvastatin as a method of decreasing biomarkers of inflammation, and they discovered that simvastatin was associated with the reduction of pulmonary and systemic injury after esophagectomy. Method of endoscopic resectional technique, extent of lymph node resection, thoracotomy versus thoracoscopy, antibiotic bowel decontamination, and prostaglandin E1 infusion have been reported in “1c” trials without differences noted in primary endpoints.
Adjuvant therapy
Preoperative Chemotherapy
There are several challenges in evaluating preoperative chemotherapy trials for esophageal cancer, because studies have variably examined squamous cell carcinoma versus adenocarcinoma and inconsistently included gastroesophageal junction and gastric cardia tumors.
A study by Boonstra and colleagues studied 171 patients with squamous cell carcinoma administered cisplatin and etoposide neoadjuvant chemotherapy. Overall survival was more favorable in the chemotherapy arm compared with patients who immediately went to surgery (5-year survival 26% vs 17%; P = .03). The US Intergroup 0113 trial randomized patients to receive perioperative cisplatin and 5-fluoracil (5-FU) or surgery alone. There were no differences in overall median or 3-year survival. Long-term follow-up confirmed these results, although a subgroup analysis revealed that patients with R1 resection seemed to benefit from postoperative chemoradiotherapy. In contrast with the Intergroup trial, the Medical Research Council Oesophageal Working Group found that preoperative cisplatin and 5-FU (at a lesser cisplatin dose of 160 mg/m 2 compared with the 450 mg/m 2 used in the Intergroup trial) conferred a survival advantage (23% vs 17%; P = .03), likely from an increased rate of R0 resections (60% vs 54%). The Medical Research Council study had a larger sample size of 467 patients and a greater number of patients who received chemotherapy going on to surgery (92% vs 80% in the Intergroup trial). The Medical Research Council preliminarily reported the results of neoadjuvant randomized trial OEO5, comparing 2 cycles of cisplatin and 5-FU with 4 cycles of epirubicin, cisplatin, and capecitabine in 897 patients. There was no survival benefit with more chemotherapy.
Several key trials grouped together distal esophagus, gastroesophageal junction, and gastric cancers in their studies. The Cunningham trial (of which 26% of patients had distal esophagus or gastroesophageal junction tumors) randomized patients to perioperative epirubicin, cisplatin, and 5-FU or surgery alone. Chemotherapy improved 5-year overall survival (36% vs 23%; P = .009). Yehou and colleagues randomized 234 patients to immediate surgery or to perioperative cisplatin and 5-FU. The 5-year survival (38% vs 24%; P = .02) and R0 resection rates (84% vs 73%, P = .04) were better in the chemotherapy group. However, a European Organisation for Research and Treatment of Cancer trial by Schuhmacher and colleagues found almost equivalent 2-year overall survival rates (70% for surgery alone vs 73% for cisplatin and 5-FU) in T3 and T4 tumors.
The standard of care in Europe for the management of esophageal cancer includes preoperative cisplatin and 5-FU. However, ongoing studies are needed to study the subgroups of patients who benefit most from neoadjuvant chemotherapy.
Preoperative Radiotherapy and Chemoradiotherapy
Randomized trials of preoperative radiation therapy alone have not increased resectability rates. Mei and colleagues reported no difference in the local failure rate, although Gignoux and colleagues noticed a lower local failure rate with preoperative radiation (46% vs 67%; P = .045). Nygaard and colleagues observed an improvement in 3-year survival (18% vs 5%; P = .009); however, some of these patients received chemotherapy. Therefore, preoperative radiation therapy alone has not been shown to improve survival endpoints consistently.
There are a few recent randomized trials that show variable results in survival and pathologic complete responses with preoperative chemoradiotherapy. These trials were limited by low statistical power, inadequacy of chemotherapy doses delivered, or unusually high postoperative mortality. The CROSS trial (Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study) by van Hagen and colleagues established preoperative chemoradiotherapy as standard of care in Western countries. The study randomized 366 patients with esophageal or gastroesophageal junction squamous cell carcinoma or adenocarcinoma to carboplatin at an area under the curve of 2 mg/mL per minute and paclitaxel 50 mg/m 2 once weekly for 5 weeks with concurrent radiotherapy (1.8 Gy daily to 41.4 Gy in 23 fractions) followed by surgery or surgery alone. There were no differences in perioperative outcomes (including postoperative mortality, <4%), and grade 3 or 4 toxicity was only seen in 13% of patients. R0 resection rates were achieved in 92% of patients versus 69% of patients in the surgery group ( P <.001). Median survival increased from 24 to 49 months (hazard ratio, 0.0657; P = .003).
Postoperative Chemotherapy
The Japanese Oncology Group has evaluated postoperative chemotherapy in several randomized trials and found no survival benefit. However, Iizuka and colleagues noticed a trend toward, though not statistically significant, improvement in disease-free survival for node-positive patients who received adjuvant chemotherapy (53% vs 35%; P = .06). Hence, survival may be prolonged in patients who had an R0 resection and lymph node–positive disease, but data are limited.
Postoperative Radiotherapy and Chemoradiotherapy
No improvement in survival was noticed in 2 randomized trials of adjuvant radiotherapy. Teniere and colleagues gave 221 patients with squamous cell carcinoma 45 to 55 Gy and observed no impact on survival. Fok and colleagues administered radiation to patients with squamous cell carcinomas and adenocarcinomas undergoing curative or palliative resections; there was no improvement in local control or median survival. Additionally, 20% of the Intergroup 0116 trial’s 603 patients had gastroesophageal junction adenocarcinoma. Patients who received postoperative chemoradiation had an increase in overall survival (50% vs 41%; P = .005), especially the group of patients who were HER2 status negative.
Definitive Radiotherapy and Chemoradiotherapy Versus Surgery
There are only 2 trials that directly compare nonoperative treatment (one with radiation alone and another with chemoradiation) with surgery. It is difficult to draw conclusions about these 2 studies because they are limited by low statistical power and short follow-up.
Radiotherapy Versus Chemoradiotherapy
There are 6 randomized trials comparing radiation with chemoradiation. However, these trials are difficult to compare because they include variable doses of radiation and systemic chemotherapy with different sequencing of therapies. An analysis of the pooled data from these trials reported a significant local control and survival benefit at 1 year for chemoradiation over radiation alone, although chemoradiation predictably increased side effects. The Eastern Cooperative Oncology Group’s EST-1282 trial also demonstrated a median overall survival benefit (15 months vs 9 months; P = .04) for patients receiving chemoradiation; however, there was no improvement in 5-year overall survival. This study was confounded by 50% of the patients in each arm undergoing surgery after radiation therapy by individual investigator’s choice. The Radiation Therapy Oncology Group 85-01 Intergroup Trail reported by Herskovic and colleagues and Al-Sarraf and colleagues examined patients who received cisplatin and 5-FU chemotherapy with 50 Gy radiation compared with patients receiving 64 Gy radiation alone. There was improved 5-year survival in patients who received chemoradiation (27% vs 0%; P <.0001).
Surgery After Chemoradiotherapy
A French study and a separate German study examined whether surgery is required after chemoradiotherapy. In the FFCD 9102 trial(Fédération Francaise de Cancérologie Digestive 9102), 444 patients with clinically resectable T3 or T4 N0 or 1 and M0 esophageal squamous cell carcinoma or adenocarcinoma all received 5-FU, cisplatin, and 46 Gy at 2 Gy per day or a split course with 15 Gy in weeks 1 and 3. Those patients who demonstrated a partial response were randomized to surgery versus additional chemoradiation. There was no difference in 2-year survival (34% vs 40%; P = .44) or median survival (17.7 months vs 19.3 months). These data suggest that patients with squamous cell carcinoma do not benefit from surgical intervention in lieu of continuing chemoradiation. A separate analysis showed that standard course radiation improved 2-year progression free survival compared with split course radiation (77% vs 57%; P = .002).
The German trial also did not show an improvement in survival in uT3 or T4 N0 or N1 and M0 disease.
Patients with squamous cell carcinoma of the esophagus undergoing surgery after definitive chemoradiation. The German Oesophageal Cancer Study Group compared preoperative chemoradiation (3 cycles of 5-FU, leucovorin, etoposide, and cisplatin, followed by concurrent etoposide, cisplatin, plus 40 Gy followed by surgery vs the same chemotherapy regimen with 60–65 Gy with or without brachytherapy). The 3-year survival (31% vs 24%) was not significantly different. These 2 trials confirm that it is reasonable from an oncologic perspective to treatment patients with squamous cell carcinoma with definitive chemoradiation.
Summary of level Ia evidence
Randomized, Controlled Trials in Esophageal Cancer
Clinical study 1
Li B, Xiang J, Zhang Y, et al. Comparison of Ivor-Lewis vs Sweet esophagectomy for esophageal squamous cell carcinoma: a randomized clinical trial. JAMA Surg 2015;150(4):292–8.
| No. Patients Randomized | Study Groups | Stratification | Significance Demonstrated | % Change Identified in Trial |
|---|---|---|---|---|
| 300 | Ivor Lewis, N = 150 Sweet, N = 150 | None | Yes, operative morbidity | 30% vs 41.3% ( P = .04) |
Hypothesis
To determine whether Ivor-Lewis esophagectomy is associated with increased postoperative complications compared with the Sweet procedure.
Published abstract
Background
Sweet esophagectomy is performed widely in China, whereas the Ivor-Lewis procedure, with potential benefit of an extended lymphadenectomy, is limitedly conducted owing to concern for a higher risk for morbidity. Thus, the role of the Ivor-Lewis procedure for thoracic esophageal cancer needs further investigation.
Methods
A randomized clinical trial was conducted from May 2010 to July 2012 at Fudan University Shanghai Cancer Center, Shanghai, China, of 300 patients with resectable squamous cell carcinoma in the middle and lower thirds of the thoracic esophagus. An intent-to-treat analysis was performed. Patients were assigned randomly to undergo either the Ivor-Lewis (n = 150) or Sweet (n = 150) esophagectomy. The primary outcome of this clinical trial was operative morbidity (any surgical or nonsurgical complications). Secondary outcomes included oncologic efficacy (number of lymph nodes resected and positive lymph nodes), postoperative mortality (30-day and in-hospital mortality), and patient discharge.
Results
Resection without macroscopic residual (R0/R1) was achieved in 149 of 150 patients in each group. Although there was no difference between the 2 groups regarding the incidence of each single complication, a significantly higher morbidity rate was found in the Sweet group (62 of 150 [41.3%]) than in the Ivor-Lewis group (45 of 150 [30%]; P = .04). More patients in the Sweet group (8 of 150 [5.3%]) underwent reoperations than in the Ivor-Lewis group (1 of 150 [0.7%]) ( P = .04). The median duration of hospital stay was 18 days in the Sweet group versus 16 days in the Ivor-Lewis group ( P = .002). Postoperative mortality rates in the Ivor-Lewis (1 of 150) and Sweet (3 of 150) groups were 0.7% and 2.0%, respectively ( P = .25). More lymph nodes were removed during Ivor-Lewis esophagectomy than during the Sweet procedure (22 vs 18; P <.001).
Conclusions
The early results of this study demonstrate that the Ivor-Lewis procedure can be performed with lower rates of postoperative complications and more lymph node retrieval. Ivor-Lewis and Sweet esophagectomies are both safe procedures with low operative mortalities.
Editor’s summary and comments
This clinical trial evaluated 2 techniques for esophagectomy, Ivor-Lewis compared with the Sweet procedure. Higher morbidity was found with the Sweet group (41.3% vs 30%; P = .04). The Sweet group had more reoperations, greater duration of stay, and fewer lymph nodes removed. This study leads to a recommendation of Ivor-Lewis esophagectomy to reduce postoperative complications and increase lymph node retrieval.
Clinical study 2
Takata A, Takiguchi S, Miyazaki Y, et al. Randomized phase II study of the anti-inflammatory effect of ghrelin during the postoperative period of esophagectomy. Ann Surg 2015;262(2):230–6.
| No. Patients Randomized | Study Groups | Stratification | Significance Demonstrated | % Change Identified in Trial |
|---|---|---|---|---|
| 40 | Ghrelin, n = 20 Placebo, n = 20 | None | Yes, systemic inflammatory response syndrome duration | 3.0 d vs 6.7 d ( P = .0062) |
Hypothesis
Ghrelin reduces systemic inflammatory response syndrome (SIRS) duration after esophagectomy.
Published abstract
Background
Esophagectomy for esophageal cancer is highly invasive and leads to prolonged SIRS duration and postoperative complications. Ghrelin has multiple effects, including antiinflammatory effects.
Methods
Forty patients undergoing esophagectomy were assigned randomly to either the ghrelin group (n = 20), which received continuous infusion of ghrelin (0.5 μg/kg/h) for 5 days, or the placebo group (n = 20), which received pure saline for 5 days. The primary endpoint was SIRS duration. The secondary endpoints were the incidence of postoperative complications, time of a negative nitrogen balance, changes in body weight and composition, and levels of inflammatory markers, including C-reactive protein and interleukin (IL)-6.
Results
The ghrelin group had a shorter SIRS duration and lower C-reactive protein and IL-6 levels than did the placebo group. The incidence of pulmonary complications was lower in the ghrelin group than in the placebo group, whereas other complications did not differ between the groups. Although time of the negative nitrogen balance was shorter in the ghrelin group than in the placebo group, changes in total body weight and lean body weight did not differ significantly.
Conclusions
Postoperative ghrelin administration was effective for inhibiting inflammatory mediators and improving the postoperative clinical course of patients with esophageal cancer.
| No. Patients Randomized | Study Groups | Stratification | Significance Demonstrated | % Change Identified in Trial |
|---|---|---|---|---|
| 67 | Decubitus, n = 32 Prone, n = 35 | None | Yes Symptom scale | 6.29 vs 3.13 ( P <.001) |
Editor’s summary and comments
This prospective, randomized, placebo-controlled phase II institutional study from Japan studied the postoperative benefit of ghrelin administration. The duration of SIRS was significantly shorter with ghrelin administration. Studies with larger sample sizes and long-term outcomes will be of benefit to clarifying the full impact of ghrelin in postesophagectomy patients.
Clinical study 3
Shen Y, Feng M, Tan L, et al. Thoracoscopic esophagectomy in prone versus decubitus position: ergonomic evaluation from a randomized and controlled study. Ann Thorac Surg 2014;98(3):1072–8.
Hypothesis
Prone positioning may provide better ergonomics.
Published abstract
Background
The prone position (PP) and decubitus position (DP) have both been used for thoracoscopic esophagectomy. However, which of these positions is ergonomically better for the operating surgeon is unknown. In this randomized, controlled trial ( NCT01144325 ), we aimed to assess the surgeon’s physical and mental stress in operating on patients in the PP compared with that in the DP.
Methods
From October 2012 to June 2013, 67 consecutive patients who underwent a 3-stage, minimally invasive esophagectomy were assigned randomly to the DP or the PP during the thoracic stage. The same senior surgeon performed all operations. Objectively, the surgeon’s spontaneous eye blink rate was recorded during thoracoscopic esophagectomy. Subjectively, the physician’s musculoskeletal symptoms were rated on a scale ranging from 1 (uninfluenced) to 10 (maximum fatigue). Clinical characteristics, including patient demographics and operative features of the 2 patient groups, were compared statistically.
Results
There were 35 patients in the PP group and 32 in the DP group. The 2 groups were comparable in patient demographics. The thoracic stage of the operation was longer in the DP group than in the PP group (87 ± 24 minutes vs 68 ± 22 minutes; P <.001), and the volume of blood loss was higher (89 ± 18 mL vs 67 ± 16 mL; P <.001). The surgeon’s eye blink rate at the end of thoracic stage decreased more from baseline in the DP group than in the PP group (3.0 ± 1.4 blinks/min vs 1.2 ± 0.9 blinks/min; P <.001), and the surgeon’s symptom scale score was higher after operation with the patient in the DP than in the PP (6.29 ± 1.54 vs 3.13 ± 2.82; P <.001). No conversion to open thoracotomy was recorded in either group.
Conclusions
Thoracoscopic esophagectomy in the PP provided less workload and better ergonomic results than the DP. Further study based on a larger number of patients is required to confirm these findings.
Editor’s summary and comments
This small, institutional, randomized trial of prone versus decubitus positioning for esophagectomy was designed to evaluate the surgeon’s mental and physical stress with each position. The musculoskeletal symptom scale was significantly higher with decubitus over prone positioning, suggesting PP may decrease surgeon workload and lead to better ergonomic results.
| No. Patients Randomized | Study Groups | Stratification | Significance Demonstrated | % Change Identified in Trial |
|---|---|---|---|---|
| 42 | Synbiotics, n = 21 Control, n = 21 | None | Yes Mesenteric lymph node samples Bacteremia | Mesenteric lymph node microorganisms: 3 vs 10 ( P = .035) Bacteremia: 4 vs 12 ( P = .025) |
Clinical study 4
Yokoyama Y, Nishigaki E, Abe T, et al. Randomized clinical trial of the effect of perioperative synbiotics versus no synbiotics on bacterial translocation after oesophagectomy. Br J Surg. 2014;101(3):189–99.
Hypothesis
Perioperative synbiotics reduce postoperative bacteremia.
Published abstract
Background
The impact of perioperative synbiotics on bacterial translocation and subsequent bacteremia after esophagectomy is unclear. This study investigated the effect of perioperative synbiotic administration on the incidence of bacterial translocation to mesenteric lymph nodes (MLNs) and the occurrence of postoperative bacteremia.
Methods
Patients with esophageal cancer were randomized to receive perioperative synbiotics or no synbiotics (control group). MLNs were harvested from the jejunal mesentery before dissection (MLN-1) and after the restoration of digestive tract continuity (MLN-2). Blood and feces samples were taken before and after operation. Microorganisms in each sample were detected using a bacterium-specific ribosomal RNA-targeted reverse transcriptase-quantitative polymerase chain reaction method.
Results
Some 42 patients were included. There was a significant difference between the 2 groups in detection levels of microorganisms in the MLN-1 samples. Microorganisms were more frequently detected in MLN-2 samples in the control group than in the synbiotics group (10 of 18 vs 3 of 18; P = .035). In addition, bacteremia detected using reverse transcriptase-quantitative polymerase chain reaction 1 day after surgery was more prevalent in the control group than in the synbiotics group (12 of 21 vs 4 of 21; P = .025). Neutrophil counts on postoperative days 1, 2, and 7 were all significantly higher in the control group than in the synbiotics group.
Conclusion
Perioperative use of synbiotics reduces the incidence of bacteria in the MLNs and blood. These beneficial effects probably contribute to a reduction in the inflammatory response after esophagectomy.
Editor’s summary and comments
This small, randomized trial studied the impact of perioperative synbiotics in patients with esophageal cancer after esophagectomy. The detection of microorganisms in MLNs and bacteremia were significantly less in the group that received synbiotics, suggesting a future role for future studies of synbiotics in the reduction of inflammatory response after esophagectomy.
Clinical study 5
Shyamsundar M, McAuley DF, Shields MO, et al. Effect of simvastatin on physiological and biological outcomes in patients undergoing esophagectomy: a randomized placebo-controlled trial. Ann Surg 2014;259(1):26–31.
| No. Patients Randomized | Study Groups | Stratification | Significance Demonstrated | % Change Identified in Trial |
|---|---|---|---|---|
| 31 | Simvastatin, n = 15 Placebo, n = 16 | None | Yes, pulmonary dead space at 6 h after esophagectomy | 94.7 h vs 113.9 h |
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