Enhanced recovery after surgery (ERAS) versus standard recovery for gastric cancer patients: The evidences and the issues

The significant advances that have been reached, in the last decades, in the treatment of gastric cancer, contributed to the concept of enhanced recovery after surgery (ERAS) with the aim to reduce the surgical stress, accelerate postoperative recovery, and reduce the length of hospital stay. The most important items included in the ERAS protocols are the pre-operative patient education, early mobilization and immediate oral intake from the first postoperative day. The aim of this narrative review is to focus the attention on the possible advantages of ERAS program on perioperative functional recovery outcomes after gastrectomy for gastric cancer.     

Enhanced recovery after surgery (ERAS) in gynecology oncology

The Enhanced Recovery After Surgery (ERAS) is a pathway designed to achieve early recovery for patients undergoing major surgery. The ERAS pathway included three important components preoperative, intraoperative, postoperative program. Pre-habilitation and re-habilitation are of paramount importance to improve patients’ care. The ERAS is based on evidence-based medicine. Accumulating evidence highlighted that adopting ERAS resulted in lower complication rate, and shorter length of hospital stay in comparison to standard protocols of care. The adoption of the ERAS resulted in a significant improvement of patients’ outcomes and a reduction of the overall cost of care. In the present review, we summarized current evidence on ERAS, focusing on the steps useful for its adoption into clinical practice.     

Prognostic impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients: A meta-analysis of randomized controlled trials

Backgroundgastric cancer patients frequently develop peritoneal metastases (PM) with a poor long-term prognosis. A solid body of evidence underlines the beneficial role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on survival, but to date, there is a lack of consensus regarding the optimal strategy in the treatment of locally advanced primary tumors with or without peritoneal metastasis. The present meta-analysis aims to assess the impact of CRS + HIPEC on survival analyzing the results of randomized studies only.MethodsA systematic review of articles was conducted according to PRISMA guidelines. Twelve studies were included in qualitative and quantitative analysis.ResultsA survival benefit for patients treated with CRS + HIPEC at all time points was highlighted. However, difference in survival was significant at all time points for patients treated for prophylaxis of PM, but no difference was found when considering resection with a curative intent. The 1, 2, 3 and 5-year survival rates (SR) for patients undergoing CRS + HIPEC were 86.9%, 70.5%, 63.7% and 55.7% respectively. CRS + HIPEC for the treatment rather than prophylaxis of PM was the only predictor of a reduced 3y SR.ConclusionsCRS + HIPEC may lead to improved prognosis for patients suffering from locally advanced gastric cancer in both prophylactic and curative settings. However, due to far from negligible postoperative morbidity and mortality rates, a strict patient selection is crucial to achieve the best results. The presence of extraperitoneal disease strongly limits the indication of this kind of surgery.     

Clinical effectiveness of neoadjuvant chemotherapy in advanced gastric cancer: An updated meta-analysis of randomized controlled trials

Aims

To assess the efficacy and safety of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (AGC).

Methods

By searching electronic databases (PubMed, Embase, Cochrane Library) and ASCO proceedings from 1990 to 2012, all randomized controlled trials (RCTs) which compared the effect of NAC-combined surgery versus surgery alone in AGC were included. All calculations and statistical tests were performed using RevMan 5.0 software.

Results

12 RCTs with a total of 1820 patients were included. All patients had locally advanced but resectable gastric cancer and received NAC. NAC can slightly improve the survival rate (OR = 1.32, 95% confidence interval (CI): 1.07–1.64, P = 0.01), with little or no significant benefits in subgroup analyses between either different population or regimens. NAC can significantly improve the 3-year progression-free survival (PFS) (OR: 1.85, 95% CI: 1.39–2.46, p < 0.0001), tumor down-staging rate (OR: 1.71, 95% CI: 1.26, 2.33, p = 0.0006) and R0 resection rate (OR: 1.38, 95% CI: 1.08–1.78, P = 0.01) of patients with AGC. There was no difference between the two arms, in terms of relapse rates (OR: 1.03, 95% CI: 0.60–1.78, p = 0.92), operative complications (OR: 1.20, 95% CI: 0.90–1.58, p = 0.21), perioperative mortality (OR: 1.14, 95% CI: 0.64–2.05, p = 0.65) and grade 3/4 adverse effects: gastrointestinal problem (OR: 0.57, 95% CI: 0.25–1.30, p = 0.18), leukopenia (OR: 0.88, 95% CI: 0.41–1.91, p = 0.75), thrombocytopenia (OR: 1.27, 95% CI: 0.27–5.93, p = 0.76).

Conclusion

NAC is effective and safe. However, further prospective multi-national and multi-center RCTs are still needed in order to investigate the long-term oncological and functional outcomes to define the clinical benefits of NAC and the most effective strategies for AGC.     

加速康复外科理念在胃癌患者围手术期中的应用及新进展

加速康复外科(ERAS)已被证实可以安全有效地应用于包括胃癌在内的多个外科领域,并在临床广泛开展,其应用范围覆盖了术前、术中和术后。目前在胃癌特殊人群中开展ERAS以及某些具体实施策略仍存有争议,胃癌ERAS的临床推广应用也面临着诸多问题。未来还需要更多高质量的循证医学证据和专业的临床实践团队来推动ERAS在胃癌领域的不断发展。     

18FDG PET-CT for detecting gastric cancer recurrence after surgical resection: A meta-analysis

BackgroundWe performed a meta-analysis to evaluate the value of ¹⁸FDG PET-CT for the detection of gastric cancer recurrence after surgical resection.MethodsA systematic literature search was performed in the MEDLINE and EMBASE databases. We calculated the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for ¹⁸FDG PET-CT. We also constructed summary receiver operating characteristic curves for ¹⁸FDG PET-CT.ResultsEight studies (500 patients) were included. The sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of ¹⁸FDG PET-CT were 0.86 (95% confidence interval [CI] = 0.71–0.94), 0.88 (95% CI = 0.75–0.94), 17.0 (95% CI = 3.5–14.0), and 0.16 (95% CI = 0.07–0.34), respectively. Overall weighted area under the curve was 0.93 (95% CI = 0.91–0.95).Conclusions¹⁸FDG PET-CT has moderate sensitivity and specificity for detection of gastric cancer recurrence after surgical resection.     

Enhanced recovery after surgery for gastric cancer and an assessment of preoperative carbohydrate loading

Background

We previously reported on the feasibility of enhanced recovery after surgery (ERAS) protocol for gastric cancer with a prospective phase II study, but the superiority of this approach over non-ERAS perioperative management remains unclear. Preoperative carbohydrate loading, an important element of the ERAS protocol, has been shown to reduce insulin resistance, but its effects on clinical endpoints in gastric cancer surgery remain controversial. The aim of this study was to clarify the efficacy of the ERAS protocol for gastric cancer surgery, with particular focus on preoperative carbohydrate loading.

加速康复外科理念在胃癌根治术中应用效果的Meta分析

目的:评价加速康复外科理念在胃癌根治术围手术期应用的有效性与安全性。方法:检索Pubmed、Embase、Cochrane Library、中国生物医学文献数据库（SinoMed）、中国知网（CNKI）、维普、万方等数据库中关于加速康复外科在胃癌根治术中应用的随机对照试验,检索时间为1995年1月至 2018年2月。两位研究人员独立进行质量评价与资料提取,采用RevMan5.2软件进行Meta分析。结果:纳入14篇文献,共1 340例患者,包括加速康复外科组669例,对照组671例。相较于对照组,加速康复外科术后首次排气时间［SMD=-1.38,95%CI（-1.89,-0.87）,P＜0.000 01］、首次排便时间［SMD=-1.62,95%CI（-2.62,-0.63）,P=0.001］缩短;住院时间［WMD=-2.26,95%CI（-2.67,-1.84）,P＜0.000 01］、住院费用［SMD=-0.65,95%CI（-1.04,-0.26）,P=0.001］减少;总并发症发生率降低［OR=0.65,95%CI（0.46,0.93）,P=0.02］。但再入院［RR=1.01,95%CI（0.24～4.36）,P=0.99］并没有明显差异。结论:加速康复外科在胃癌根治术围手术期中应用是安全有效的,有利于促进患者的康复,具有临床应用价值,但需要更多高质量的循证证据支持。     

Outcomes of Enhanced Recovery after Surgery (ERAS) in Gynecologic Oncology: A Review

Enhanced Recovery After Surgery (ERAS) is a global surgical quality improvement program that started in colorectal surgery and has now expanded to numerous specialties, including gynecologic oncology. ERAS guidelines comprise multidisciplinary, evidence-based recommendations in the preoperative, intraoperative, and postoperative period; these interventions broadly encompass patient education, anesthetic choice, multimodal pain control, avoidance of unnecessary drains, maintenance of nutrition, and prevention of emesis. Implementation of ERAS has been shown to be associated with improved clinical outcomes (length of hospital stay, complications, readmissions) and cost. Marx and colleagues first demonstrated the feasibility of ERAS in gynecologic oncology in 2003; since then, over 30 comparative studies and 4 guidelines have been published encompassing major gynecologic surgery, cytoreductive surgery, and vulvar/vaginal surgery. Implementation of ERAS in gynecologic oncology has been demonstrated to provide improvements in length of stay, complications, cost, opioid use, and patient satisfaction. Increased compliance with ERAS guidelines has been associated with greater improvement in outcomes.     

Application of venous thromboembolism prophylaxis program in patients with colorectal cancer using the enhanced recovery after surgery protocol

IntroductionThe incidence of postoperative symptomatic venous thromboembolism (VTE) in western colorectal cancer is 1.1–2.5%. Anticoagulation and mechanical devices are recommended for moderate-to high-risk patients. Hospital stay and immobilization, as risk factors for VTE, are reduced by enhanced recovery after surgery (ERAS). This study aimed to evaluate short- and long-term outcomes for a VTE prophylaxis program after minimally invasive colorectal cancer surgery with ERAS protocol. In addition, predicting factors associated with VTE were investigated.Materials and methodsWe included 1043 patients diagnosed with colorectal cancer who required surgical treatment between January 2017 and December 2019 at a single institution. The patients enrolled followed the VTE prophylaxis program.ResultsFive (0.5%) patients developed symptomatic VTE, and the median follow-up period was 21 months. The Caprini score for all VTE patients was ≤8 points; thus, only mechanical prophylaxis was applied. The incidence rate of postoperative symptomatic VTE was only 0.5%. There was no association between variables considered as associated with VTE onset, such as age, perioperative complication, and length of postoperative day. TNM staging (OR 2.44, 95% CI 1.4–4.16, p = 0.001) and the Caprini score (OR 1.75, 95% CI 1.1–2.8, p = 0.001) were associated with VTE onset.ConclusionAlthough pharmacological prophylaxis was only performed for Caprini scores ≥9, the VTE incidence rate of patients with colorectal cancer undergoing VTE prophylaxis program was 0.6%; 0.7% is the incidence criterion of the moderate group recommended for pharmacological prophylaxis. Continuous follow-up is required for patients with advanced-stage colorectal cancer with high-risk Caprini scores.     

Pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy: A meta-analysis of randomized control trials

Background

Postoperative pancreatic fistula (PF) is the leading morbidity after pancreaticoduodenectomy (PD). The pancreatoenteric anastomosis method after PD is associated with the occurrence of PF. Evidence shows that pancreaticogastrostomy (PG) is possibly superior to pancreaticojejunostomy (PJ) in reducing the incidence of PF after PD; however, this remains to be definitively confirmed.

Methods

Randomized clinical trials (RCTs) comparing the outcomes of PG versus PJ after PD were retrieved for meta-analysis.

Results

After a thorough search of the English literature published until March 23rd, 2014, we identified seven RCTs involving 1095 patients (PG group, 548; PJ group, 547) for final analysis. Meta-analysis revealed that the incidence of PF was significantly lower in the PG group (15.7%) than in the PJ group (23.0%, 126/547; OR = 0.61, 95% CI: 0.45–0.83, P = 0.002). Furthermore, the incidence of intra-abdominal fluid collection was also lower in the PG group than in the PJ group (OR = 0.43, 95% CI: 0.28–0.65, P < 0.0001). No significant differences were found between the PG and PJ groups in terms of delayed gastric emptying, hemorrhage, overall morbidity and mortality.

Conclusions

PG seemed to be superior to PJ in reducing the incidence of PF and intra-abdominal fluid collection after PD.     

Perioperative nutrition and enhanced recovery after surgery in gastrointestinal cancer patients. A position paper by the ESSO task force in collaboration with the ERAS society (ERAS coalition)

Malnutrition in cancer patients – in both prevalence and degree – depends primarily on tumor stage and site. Preoperative malnutrition in surgical patients is a frequent problem and is associated with prolonged hospital stay, a higher rate of postoperative complications, higher re-admission rates, and a higher incidence of postoperative death. Given the focus on the cancer and its cure, nutrition is often neglected or under-evaluated, and this despite the availability of international guidelines for nutritional care in cancer patients and the evidence that nutritional deterioration negatively affects survival. Inadequate nutritional support for cancer patients should be considered ethically unacceptable; prompt nutritional support must be guaranteed to all cancer patients, as it can have many clinical and economic advantages. Patients undergoing multimodal oncological care are at particular risk of progressive nutritional decline, and it is essential to minimize the nutritional/metabolic impact of oncological treatments and to manage each surgical episode within the context of an enhanced recovery pathway. In Europe, enhanced recovery after surgery (ERAS) and routine nutritional assessment are only partially implemented because of insufficient awareness among health professionals of nutritional problems, a lack of structured collaboration between surgeons and clinical nutrition specialists, old dogmas, and the absence of dedicated resources. Collaboration between opinion leaders dedicated to ERAS from both the European Society of Surgical Oncology (ESSO) and the ERAS Society was born with the aim of promoting nutritional assessment and perioperative nutrition with and without an enhanced recovery program. The goal will be to improve awareness in the surgical oncology community and at institutional level to modify current clinical practice and identify optimal treatment options.     

An updated meta-analysis of adjuvant chemotherapy after curative resection for gastric cancer

Objectives

To investigate whether and how much gastric cancer patients after curative resection could benefit from chemotherapy.

Patients and methods

Meta-analysis was conducted with all the qualified clinical randomized trials which compared adjuvant chemotherapy with surgery alone. The database includes MEDLINE, EMBase and CBM disc, and the censor data were up to November 2007. Primary outcomes were relative risk (RR) on death and disease-free survival (DFS); secondary outcomes include RR of adverse reactions of the two arms. Sub-group analysis and sensitivity analysis were also performed. All the calculations and statistical tests were done with the RevMan 4.2.8 software.

Results

Finally, 23 trials which included 4919 patients (2441 in the adjuvant chemotherapy arm, 2478 in the observation arm) achieved all the criteria. Among them, 19 studies reported the survival rate at the end of follow-up, 60.6% alive among 2286 patients in the adjuvant chemotherapy arm, 53.4% alive among 2313 patients in the observation arm, with the RR on death of 0.85 (95%CI: 0.80–0.90). Eight studies reported the DFS, and the observation arm had a shorter DFS (RR: 0.88, 95%CI: 0.77–0.99). Grade 3/4 of myelosuppression and GI toxicity occurred more frequently in the treatment arm. Nine studies reported the recurrence rate and suggested that the treatment arm had a lower recurrence rate (RR: 0.78, 95%CI: 0.71∼0.86).

Conclusions

Statistically, adjuvant chemotherapy could improve the survival rate and disease-free survival rate in gastric cancer after curative resection and reduce the relapse rate. However, the clinical benefits of adjuvant chemotherapy still need to be improved. Additionally, post-operative chemotherapy could be tolerated.     

Prospective study of the effect of ERAS on postoperative recovery and complications in patients with gastric cancer

Objective:To study the efficacy of the enhanced recovery after surgery (ERAS) program on postoperative recovery and complications in patients with gastric cancer.Methods:Eighty patients in the perioperative period with radical gastrectomy were enrolled and randomly divided into 2 groups, the ERAS group and the non-ERAS group. The differences between the 2 groups in terms of postoperative recoveries and complications rate were determined. According to the body mass index (BMI) level, the ERAS group was divided into 2 subgroups, namely group A (BMI < 28 kg/m², n = 16) and group B (BMI ≥ 28 kg/m², n = 24). The non-ERAS group was also divided into group C (BMI < 28 kg/m², n = 18) and group D (BMI ≥ 28 kg/m², n = 22). The recovery and complications of each group were then determined.Results:The postoperative length of stay and visual analogue scale pain score were less in the ERAS group than the non-ERAS group (P < 0.05). Time to first postoperative exhaustion, first postoperative defecation, returning leukocyte count to normal, and stopping intravenous nutrition were significantly shorter in the ERAS group (n = 40), compared to the non-ERAS group (n = 40, all P < 0.05). The incidence of postoperative lower extremity intramuscular venous thrombosis was significantly higher in group D than in group B (χ² = 4.800, P = 0.028). In addition, the incidence of lower extremity intermuscular venous thrombosis and lung infection in group D was higher than those in other groups.Conclusions:The perioperative ERAS program was associated with faster recovery in patients undergoing radical gastrectomy. For patients with higher BMI (BMI ≥ 28 kg/m²), the use of the perioperative ERAS program was more advantageous.     

Survival after radiotherapy in gastric cancer: Systematic review and meta-analysis

Background and purpose

A systematic review and meta-analysis was performed to assess the impact of radiotherapy on both 3- and 5-year survival in patients with resectable gastric cancer.

Methods

Randomized Clinical Trials (RCTs) in which radiotherapy, (preoperative, postoperative and/or intraoperative), was compared with surgery alone or surgery plus chemotherapy in resectable gastric cancer were identified by searching web-based databases and supplemented by manual examination of reference lists. Meta-analysis was performed using Risk Ratios (RRs). Random or fixed effects models were used to combine data. The methodological quality was evaluated by Chalmers’ score.

Results

Radiotherapy had a significant impact on 5-year survival. Using an intent to treat (ITT) and a Per Protocol (PP) analysis, the overall 5-year RR was 1.26 (95% CI: 1.08-1.48; NNT = 17) and 1.31 (95% CI: 1.04-1.66; NNT = 13), respectively. Although the quality of the studies was variable, the data were consistent and no clear publication bias was found.

Conclusion

This meta-analysis showed a statistically significant 5-year survival benefit with the addition of radiotherapy in patients with resectable gastric cancer. Radiotherapy remains a standard component in the treatment of resectable gastric cancer and new RCTs need to address the impact of new conformal radiotherapy technologies.     

Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of randomized trials

Introduction

An important component of treatment failure in gastric cancer (GC) is cancer dissemination within the peritoneal cavity and nodal metastasis. Intraperitoneal chemotherapy (IPC) is considered to give a fundamental contribute in treating advanced GC. The purpose of the study is to investigate the effects of IPC in patients with advanced GC.

Material and methods

A systematic review with meta-analysis of randomized controlled trials (RCTs) of IPC + surgery vs. control in patients with advanced GC was performed.

Results

Twenty prospective RCTs have been included (2145 patients: 1152 into surgery + IPC arm and 993 into control arm). Surgery + IPC improves: 1, 2 and 3-year mortality (OR = 0.31, 0.27, 0.29 respectively), 2 and 3-year mortality in patients with loco-regional nodal metastasis (OR = 0.28, 0.16 respectively), 1 and 2-year mortality rate in patients with serosal infiltration (OR = 0.33, 0.27 respectively). Morbidity rate was increased by surgery + IPC (OR = 1.82). The overall recurrence and the peritoneal recurrence rates were improved by surgery + IPC (OR = 0.46 and 0.47 respectively). There was no statistically significant difference in lymph-nodal recurrence rate. The rate of haematogenous metastasis was improved by surgery + IPC (OR = 0.63).

Conclusions

1, 2 and 3-year overall survival is incremented by the IPC. No differences have been found at 5-year in overall survival rate. 2 and 3-year mortality rates in patients with nodal invasion and 1 and 2-year mortality rates in patients with serosal infiltration are improved by the use of IPC. IPC has positive effect on peritoneal recurrence and distant metastasis. Morbidity rate is incremented by IPC. Loco-regional lymph-nodes invasion in patients affected by advanced gastric cancer is not a contraindication to IPC.     

促进术后恢复理念对经尿道内镜黏膜下膀胱肿瘤海博刀剥离术患者术后康复的影响

目的:探究运用促进术后恢复理念（ERAS）在经尿道内镜黏膜下膀胱肿瘤海博刀剥离术（BT-ESD）患者围手术期护理中的临床成效。方法:选取我院2015年5月至2017年5月入院的非肌层浸润性膀胱肿瘤患者98例，通过随机分组法将其分为ERAS组和对照组，每组49例。ERAS组应用ERAS理念，对照组患者护理方法为常规基础护理。两组患者均接受BT-ESD。针对术后患者恢复时间情况、术后并发症发生率等观察指标对两组患者进行对比分析。结果:术后患者饥饿程度评分，对照组轻度、中度及重度饥饿比例分别为46.9%、49.0%及4.1%，饥饿严重程度显著高于ERAS组（87.8%、12.2%及0.0%）（P<0.05）；而术后患者口渴程度评分，对照组的严重程度亦显著高于ERAS组（轻度、中度及重度口渴比例分别4.1% vs 32.6%、20.4% vs 40.8%、75.5% vs 26.5%）（P<0.05）。进一步研究发现除术后住院时间外，ERAS组患者术后疼痛视觉模拟评分（VAS）（5.9分 vs 3.1分）、通气时间（12小时 vs 8小时）、尿管拔除时间（2.5天 vs 2天）、膀胱痉挛次数（3次 vs 1.8次）及膀胱冲洗时间（9.0小时 vs 6.0小时）均显著优于对照组（P值均<0.05）。结论:ERAS可以显著改善BT-ESD患者围手术期护理效果，具体体现在:缩短患者膀胱冲洗时间、尿管拔除时间、肠道通气时间；降低术后不良反应发生率，显著增加患者满意度，应在临床广泛推广应用。     

Laparoscopic versus open distal gastrectomy for advanced gastric cancer: A meta-analysis of randomized controlled trials and high-quality nonrandomized comparative studies

BackgroundControversy persists about the effects of laparoscopic distal gastrectomy (LDG) versus open distal gastrectomy (ODG) on short-term surgical outcomes and long-term survival within the field of advanced gastric cancer (AGC).MethodsStudies published from January 1994 to February 2020 that compare LDG and ODG for AGC were identified. All randomized controlled trials (RCTs) were included. The selection of high-quality nonrandomized comparative studies (NRCTs) was based on a validated tool (Methodological Index for Nonrandomized Studies, MINORS). The short- and long-term outcomes of both procedures were compared.ResultsOverall, 30 studies were included in this meta-analysis, which comprised of 8 RCTs and 22 NRCTs involving 16,029 patients (7864 LDGs, 8165 ODGs). The recurrence, 3-year disease-free survival (DFS), 3-year overall survival (OS), and 5-year OS rates for LDG and ODG were comparable. LDG was associated with a lower postoperative complication rate (OR 0.79; P < 0.00001), lower estimated volume of blood loss (WMD -102.21 mL; P < 0.00001), shorter postoperative hospital stay (WMD -1.96 days; P < 0.0001), shorter time to first flatus (WMD -0.54 day; P = 0.0007) and shorter time to first liquid diet (WMD -0.66 day; P = 0.001). The number of lymph nodes retrieved, mortality, intraoperative complications, intraoperative blood transfusion, and time to ambulation were similar. However, LDG was associated with a longer surgical time (WMD 33.57 min; P < 0.00001).ConclusionsLDG with D2 lymphadenectomy is a safe and effective technique for patients with AGC when performed by experienced surgeons at high-volume specialized centers.