Koshi Kumagai

Meta-analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal and gastro-oesophageal junctional cancers

The long‐term survival benefits of neoadjuvant chemotherapy (NAC) and chemoradiotherapy (NACR) for oesophageal carcinoma are well established. Both are burdened, however, by toxicity that could contribute to perioperative morbidity and mortality.

Survival benefit and additional value of preoperative chemoradiotherapy in resectable gastric and gastro-oesophageal junction cancer: A direct and adjusted indirect comparison meta-analysis

Several phase I/II studies of chemoradiotherapy for gastric cancer have reported promising results, but the significance of preoperative radiotherapy in addition to chemotherapy has not been proven. In this study, a systematic literature search was performed to capture survival and postoperative morbidity and mortality data in randomised clinical studies comparing preoperative (chemo)radiotherapy or chemotherapy versus surgery alone, or preoperative chemoradiotherapy versus chemotherapy for gastric and/or gastro-oesophageal junction (GOJ) cancer. Hazard ratios (HRs) for overall mortality were extracted from the original studies, individual patient data provided from the principal investigators of eligible studies or the earlier published meta-analysis. The incidences of postoperative morbidities and mortalities were also analysed. In total 18 studies were eligible and data were available from 14 of these. The meta-analysis on overall survival yielded HRs of 0.75 (95% CI 0.65-0.86, P < 0.001) for preoperative (chemo)radiotherapy and 0.83 (95% CI 0.67-1.01, P = 0.065) for preoperative chemotherapy when compared to surgery alone. Direct comparison between preoperative chemoradiotherapy and chemotherapy resulted in an HR of 0.71 (95% CI 0.45-1.12, P = 0.146). Combination of direct and adjusted indirect comparisons yielded an HR of 0.86 (95% CI 0.69-1.07, P = 0.171). No statistically significant differences were seen in the risk for postoperative morbidity or mortality between preoperative treatments and surgery alone, or preoperative (chemo)radiotherapy and chemotherapy. Preoperative (chemo)radiotherapy for gastric and GOJ cancer showed significant survival benefit over surgery alone. In comparisons between preoperative chemotherapy and (chemo)radiotherapy, there is a trend towards improved survival when adding radiotherapy, without increased postoperative morbidity or mortality.

Predictors for failure of stent treatment for benign esophageal perforations - a single center 10-year experience.

AIM To investigate possible predictors for failed self-expandable metallic stent (SEMS) therapy in consecutive patients with benign esophageal perforation-rupture (EPR). METHODS All patients between 2003-2013 treated for EPR at the Karolinska University Hospital, a tertiary referral center, were studied with regard to initial management with SEMS. Patients with malignancy as an underlying cause and those with anastomotic leakages were excluded. Sealing of the perforation with a covered SEMS was the primary strategy whenever feasible. Stent therapy failure was defined as a radical change of treatment strategy due to uncontrolled mediastinitis, which in this setting consisted of emergency esophagectomy with end-esophagostomy or death as a consequence of the perforation and subsequent uncontrolled sepsis. Patient and lesion characteristics were analyzed and are presented as median and interquartile range. Possible predictors for failed stent therapy were analyzed with uni-variate logistic regression, while variables with P < 0.2 were further analyzed with multi-variate logistic regression. RESULTS Of the total number of 48 patients presenting with EPR, 40 patients (83.3%) were treated with SEMS at the time of admission, with an intention to heal the perforation. Twenty-three patients had Boerhaaves syndrome (58%), 16 had an iatrogenic perforation (40%) and 1 had external trauma to the esophagus (3%). The total in-hospital mortality, including the cases that had other initial treatments (n = 8), was 10.4% and 7.5% among those who were subjected to the SEMS-based strategy. In 33 of the 40 patients (82.5%) who were treated with stent, the EPR healed without further change in treatment strategy. Patients classified as treatment success received a SEMS at a median time of 1 (1-1) d after the actual EPR, compared to 3 (1-10) d among those where the initial treatment failed, P = 0.039 in uni-variate analysis and P = 0.052 in multi-variate analysis. No other significant factors emerged, indicating an increased risk for failure. Six of 7 patients, where stent treatment of the defect failed, underwent an emergency esophagectomy with end esophagostomy and one patient died. CONCLUSION SEMS as an upfront therapeutic strategy seems to be a successful concept, when applied to an unselected group of patients with EPR.

Per-oral endoscopic myotomy for achalasia. Are results comparable to laparoscopic Heller myotomy?

Abstract Objective. Per-oral endoscopic myotomy (POEM) has recently been introduced as a minimal invasive alternative to conventional treatment for achalasia. This study aimed to clarify the feasibility and the short-term clinical efficacy of POEM as compared to laparoscopic Heller myotomy (LHM). Methods. Treatment outcomes were prospectively recorded and compared between the procedures in a nonrandomized fashion. Reduction rate (RR) in timed barium esophagogram (TBE) was calculated at 1, 2 and 5 min after barium ingestion as: RR = 1− postoperative barium height/preoperative barium height. Risk factors for treatment failure defined as the proportion of patients with RR <0.5 (1 min) and gastroesophageal reflux (GER) after POEM were analyzed. Results. Forty-two consecutive patients who underwent POEM were compared to 41 patients who had a LHM during the immediate time period prior to the introduction of POEM. Ninety percent of the cases reported complete symptom relief after POEM. The percentage of esophageal emptying and RR in TBE improved dramatically by both procedures without significant difference. A longer operation time (odds ratio [OR] 32.80, 95%CI 2.99–359.82, p = 0.004) and younger age (OR 26.81, 95%CI 2.09–344.03, p = 0.012) were the independent predictors of treatment failure after POEM. GER was observed in seven patients where previous dilatation (OR 8.59, 95%CI 1.16–63.45, p = 0.035) and higher body mass index (OR 8.69, 95%CI 1.13–66.63, p = 0.037) were the independent predictors for symptomatic GER after POEM. Conclusion. POEM seems to be a safe and effective treatment option for achalasia in the short-term perspective; an effect well comparable to LHM.

Treatment of esophageal anastomotic leakage with self-expanding metal stents: analysis of risk factors for treatment failure

Background and study aim: The endoscopic placement of self-expandable metallic esophageal stents (SEMS) has become the preferred primary treatment for esophageal anastomotic leakage in many institutions. The aim of this study was to investigate possible risk factors for failure of SEMS-based therapy in patients with esophageal anastomotic leakage. Patients and methods: Beginning in 2003, all patients with an esophageal leak were initially approached and assessed for temporary closure with a SEMS. Until 2014, all patients at the Karolinska University Hospital with a leak from an esophagogastric or esophagojejunal anastomosis were identified. Data regarding the characteristics of the patients and leaks and the treatment outcomes were compiled. Failure of the SEMS treatment strategy was defined as death due to the leak or a major change in management strategy. The risk factors for treatment failure were analyzed with simple and multivariable logistic regression statistics. Results: A total of 447 patients with an esophagogastric or esophagojejunal anastomosis were identified. Of these patients, 80 (18 %) had an anastomotic leak, of whom 46 (58 %) received a stent as first-line treatment. In 29 of these 46 patients, the leak healed without any major change in treatment strategy. Continuous leakage after the application of a stent, decreased physical performance preoperatively, and concomitant esophagotracheal fistula were identified as independent risk factors for failure with multivariable logistic regression analysis. Conclusion: Stent treatment for esophageal anastomotic leakage is successful in the majority of cases. Continuous leakage after initial stent insertion, decreased physical performance preoperatively, and the development of an esophagotracheal fistula decrease the probability of successful treatment.

Nutritional route in oesophageal resection trial II (NUTRIENT II): study protocol for a multicentre open-label randomised controlled trial

Introduction Early start of an oral diet is safe and beneficial in most types of gastrointestinal surgery and is a crucial part of fast track or enhanced recovery protocols. However, the feasibility and safety of oral intake directly following oesophagectomy remain unclear. The aim of this study is to investigate the effects of early versus delayed start of oral intake on postoperative recovery following oesophagectomy. Methods and analysis This is an open-label multicentre randomised controlled trial. Patients undergoing elective minimally invasive or hybrid oesophagectomy for cancer are eligible. Further inclusion criteria are intrathoracic anastomosis, written informed consent and age 18 years or older. Inability for oral intake, inability to place a feeding jejunostomy, inability to provide written consent, swallowing disorder, achalasia, Karnofsky Performance Status <80 and malnutrition are exclusion criteria. Patients will be randomised using online randomisation software. The intervention group (direct oral feeding) will receive a liquid oral diet for 2 weeks with gradually expanding daily maximums. The control group (delayed oral feeding) will receive enteral feeding via a jejunostomy during 5 days and then start the same liquid oral diet. The primary outcome measure is functional recovery. Secondary outcome measures are 30-day surgical complications; nutritional status; need for artificial nutrition; need for additional interventions; health-related quality of life. We aim to recruit 148 patients. Statistical analysis will be performed according to an intention to treat principle. Results are presented as risk ratios with corresponding 95% CIs. A two-tailed p<0.05 is considered statistically significant. Ethics and dissemination Our study protocol has received ethical approval from the Medical research Ethics Committees United (MEC-U). This study is conducted according to the principles of Good Clinical Practice. Verbal and written informed consent is required before randomisation. All data will be collected using an online database with adequate security measures. Trial registration numbers NCT02378948 and Dutch trial registry: NTR4972; Pre-results.

Relief of dysphagia during neoadjuvant treatment for cancer of the esophagus or gastroesophageal junction

Dysphagia is the main symptom of cancer of the esophagus and gastroesophageal junction and causing nutritional problems and weight loss, often counteracted by insertion of self-expandable metal stents or nutrition via an enteral route. Clinical observations indicate that neoadjuvant therapy may effectively and promptly alleviate dysphagia, making such nutrition supportive interventions redundant before surgical resection. The objective of the current study was to carefully study the effects of induction neoadjuvant therapy on dysphagia and its subsequent course and thereby investigate the actual need for alimentary gateways for nutritional support. Thirty-five consecutive patients scheduled for neoadjuvant therapy were recruited and assessed regarding dysphagia and appetite at baseline, after the first cycle of preoperative treatment with either chemotherapy alone or with chemoradiotherapy and before surgery. Platinum-based therapy in combination with 5-fluorouracil was administered intravenously days 1-5 every 3 weeks and consisted of three treatments. Patients receiving combined chemoradiotherapy started radiotherapy on day one of second chemotherapy cycle. They received fractions of 2 Gy/day each up to a total dose of 40 Gy. Watson and Ogilvie dysphagia scores were used to assess dysphagia, while appetite was assessed by the Edmonton Assessment System Visual analogue scale-appetite questionnaire. Patients were evaluated at regular outpatient clinic visits or by telephone. The histological tumor response in the surgical specimen was assessed using the Chirieac scale. Ten patients scheduled for neoadjuvant chemotherapy and 25 patients scheduled for chemoradiotherapy were included in the analysis. There was a significant improvement in dysphagia in both treatment groups, according to both scales, already from baseline to the completion of the first chemotherapy cycle which remained to the end of the neoadjuvant treatment (P < 0.001). Appetite also improved after the first chemotherapy cycle (P = 0.03). Body weight did not change during any type of neoadjuvant therapy. We were unable to demonstrate any association between relief of dysphagia and the degree of histological response to neoadjuvant therapy in the surgical specimen. The present study shows that a platin - 5FU-based neoadjuvant chemotherapy, with or without concomitant radiotherapy, effectively and promptly relieves dysphagia in patients presenting with cancers of the esophagus or gastroesophageal junction already after the first cycle.

Nasogastric decompression following esophagectomy: a systematic literature review and meta-analysis.

Routine use of nasogastric tubes for gastric decompression has been abolished in nearly all types of gastro-intestinal surgery after introduction of enhanced recovery after surgery programs. However, in esophagectomy the routine use of nasogastric decompression is still a matter of debate. To determine the effects of routine nasogastric decompression following esophagectomy compared with early or peroperative removal of the nasogastric tube on pulmonary complications, anastomotic leakage, mortality, and postoperative recovery. A systematic literature review and meta-analysis of studies comparing early or peroperative versus late removal of nasogastric tubes. A total of seven comparative studies were included (n = 608). In two randomized trials, and one retrospective cohort study, peroperative removal of the nasogastric tube was compared with routine nasogastric decompression. In one randomized trial early removal of the nasogastric tube (on postoperative day 2) was compared with removal of the nasogastric tube on the 6th-10th postoperative day. In the remaining three trials a fast-track protocol without a nasogastric tube was compared with conventional care with a nasogastric tube during the first postoperative days. Peroperative or early removal of the nasogastric tube did not result in a significantly different rate of anastomotic leakage, pulmonary complications or mortality in individual studies, nor in the meta-analysis. In the meta-analysis, hospital stay was significantly shorter with peroperative or early removal of the nasogastric tube when all studies were included, but not when the meta-analysis was limited to randomized trials. This systematic review did not find a difference in adverse outcomes between nasogastric decompression or no nasogastric decompression following esophagectomy.