Staging laparoscopy with peritoneal lavage to identify peritoneal metastases and free intraperitoneal cancer cells in the management of locally advanced gastric cancer.

INTRODUCTION: Gastric cancer often presents in advanced stage with a significant risk for peritoneal dissemination. Staging laparoscopy can be used to detect peritoneal carcinomatosis (PC+) and free cancer cells in peritoneal lavage cytology (CY+). The current study aimed to present the outcomes of staging laparoscopy and the prognosis of PC+ and CY+ in a Swedish high-volume center. MATERIALS AND METHODS: A cohort study including all consecutive patients with locally advanced gastric cancer who underwent staging laparoscopy between February 2008 and October 2022. The laparoscopy findings were categorized as PC+, PC-CY+ (positive cytology without peritoneal carcinomatosis) or negative laparoscopy (PC-CY-). The primary endpoint was overall survival (OS) stratified by laparoscopy findings. The secondary endpoint was OS within each laparoscopy finding group stratified by subsequent treatment. RESULTS: Among 168 patients who underwent staging laparoscopy, 78 patients (46%) had PC-CY-, 29 patients (17%) had PC-CY+ and 61 patients (36%) had PC+. Decreased OS was observed for both PC-CY+ patients (aHR 2.14, 95% CI 1.13-4.06) and PC+ patients (aHR 5.36, 95% CI 3.21-8.93), compared to PC-CY-. Patients with PC-CY+ who converted to PC-CY- after chemotherapy and underwent tumor resection seemed to have a better prognosis compared to patients with persisting PC-CY+. CONCLUSIONS: Staging laparoscopy is an important tool in the staging of locally advanced gastric cancer. Tumor resection for patients with PC-CY+ who convert to PC-CY- may lead to improved survival for these patients.

Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial.

BACKGROUND: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer. PATIENTS AND METHODS: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type. RESULTS: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107). CONCLUSION: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.

Feasibility and Safety of Laparoscopic D2 Gastrectomy in Combination with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients with Gastric Cancer at High Risk of Recurrence-The PIPAC-OPC4 Study.

BACKGROUND: Patients with gastric adenocarcinoma (GAC) are at high risk of peritoneal recurrence despite perioperative chemotherapy and radical resection. This study evaluated feasibility and safety of laparoscopic D2 gastrectomy in combination with pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS: This was a prospective, controlled bi-institutional study in patients with GAC at high risk of recurrence treated with PIPAC with cisplatin and doxorubicin (PIPAC C/D) after laparoscopic D2 gastrectomy. High risk was defined as a poorly cohesive subtype with predominance of signet-ring cells, clinical stage ≥ T3 and/or ≥ N2, or positive peritoneal cytology. Peritoneal lavage fluid was collected before and after resection. Cisplatin (10.5 mg/m2) and doxorubicin (2.1 mg/m2) were aerosolized after anastomosis (flow 0.5-0.8 ml/s, maximum pressure 300 PSI). Treatment was feasible and safe if ≤ 20% had Dindo-Clavien ≥ 3b surgical complications or CTCAE ≥ 4 medical adverse events within 30 days. Secondary outcomes were length of stay (LOS), peritoneal lavage cytology, and completion of postoperative systemic chemotherapy. RESULTS: Twenty-one patients were treated with a D2 gastrectomy and PIPAC C/D. The median age was 61 years (range 24-76), there were eleven female patients, and 20 patients had preoperative chemotherapy. There was no mortality. Two patients had grade 3b complications that were potentially related to PIPAC C/D (one anastomotic leakage, and one late duodenal blow-out). One patient had severe neutropenia, and nine patients had moderate pain. The LOS was 6 days (4-26). One patient had positive peritoneal lavage cytology before resection, and none were positive after. Fifteen patients had postoperative chemotherapy. CONCLUSIONS: Laparoscopic D2 gastrectomy in combination with PIPAC C/D is feasible and safe.

Cardiorespiratory Comorbidity and Postoperative Complications following Esophagectomy: a European Multicenter Cohort Study.

BACKGROUND: The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on postoperative complications for patients treated for esophageal or gastroesophageal junction cancer. PATIENTS AND METHODS: A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed. RESULTS: In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien-Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11-3.04], pneumonia (OR 1.65, 95% CI 1.10-2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04-2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien-Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia. CONCLUSIONS: The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk.

Meta-analysis of risk factors and complications associated with atrial fibrillation after oesophagectomy.

BACKGROUND: Oesophagectomy is associated with high morbidity and mortality rates. New-onset atrial fibrillation (AF) is a frequent complication following oesophagectomy. Several studies have explored whether new-onset AF is associated with adverse events after oesophagectomy. METHODS: This review was performed according to PRISMA guidelines. Eligible studies were identified through a search of PubMed, Scopus and Cochrane CENTRAL databases up to 25 November 2018. A meta-analysis was conducted with the use of random-effects modelling. The I2 statistic was used to assess for heterogeneity. RESULTS: In total, 53 studies including 9087 patients were eligible for analysis. The overall incidence of postoperative AF was 16·5 per cent. Coronary artery disease and hypertension were associated with AF, whereas diabetes, smoking and chronic obstructive pulmonary disease were not. Patients with AF had a significantly higher risk of overall postoperative adverse events than those without fibrillation (odds ratio (OR) 5·50, 95 per cent c.i. 3·51 to 8·30), including 30-day mortality (OR 2·49, 1·70 to 3·64), anastomotic leak (OR 2·65, 1·53 to 4·59) and pneumonia (OR 3·42, 2·39 to 4·90). CONCLUSION: Postoperative AF is frequently observed in patients undergoing oesophagectomy for cancer. It is associated with an increased risk of death and postoperative complications.

Effects of neoadjuvant chemoradiotherapy vs chemotherapy alone on the relief of dysphagia in esophageal cancer patients: secondary endpoint analysis in a randomized trial.

Dysphagia is the most significant symptom in patients with esophageal cancer. There are different therapeutic interventions designed to relieve dysphagia, but few studies have addressed the effects of neoadjuvant therapy. The aim of this study is to compare the effects on dysphagia of neoadjuvant chemotherapy (nCT) versus neoadjuvant chemoradiotherapy (nCRT) and further to study the association between dysphagia response and histological response. Patient reported swallowing function was a secondary endpoint in the NeoRes trial, in which patients were randomized between neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy. Patients completed dysphagia questionnaires before the start and after neoadjuvant therapy, using the European Organization for Research and Treatment of Cancer (EORTC) esophageal cancer modules QLQ-OES24/OG25. Chirieac tumor regression grade (TRG) was used to assess the histological response. Out of 181 patients were randomized, of whom 87% completed the dysphagia questionnaires before and 73% after neoadjuvant treatment. Patient characteristics were similar between the treatment arms. Among patients reporting dysphagia at baseline, neoadjuvant therapy improved dysphagia in both arms. The mean dysphagia score after neoadjuvant treatment was significantly lower after nCT compared to after nCRT (P = 0.022). The reported dysphagia did not differ between those with a complete histological response (TRG 1) and those without any response at all (TRG 4) (P = 0. 583).

Texture analysis of computed tomography data using morphologic and metabolic delineation of esophageal cancer-relation to tumor type and neoadjuvant therapy response.

The prognostic values of image-based tumor texture analysis based on computed tomography (CT) and of limiting the segmented tumor volume to metabolically active regions using fludeoxyglucose-positron emission tomography (FDG-PET) were studied in 25 patients with esophageal adenocarcinoma and 11 patients with squamous cell carcinoma. The aims of this study are to describe their CT-image-based texture characteristics before and after neoadjuvant therapy and to evaluate whether limiting the examined tumor volume to metabolically active regions detected with FDG-PET image data would further improve their value. Textural parameters (homogeneity, energy, entropy, contrast, and correlation) based on gray-level co-occurrence matrices (GLCM) were calculated for 3D volumes of segmented esophageal tumors before and after neoadjuvant chemotherapy or radiochemotherapy. Histopathological data after surgical resection and textural parameters before and after neoadjuvant treatment were compared using the Mann-Whitney U test. Significant differences in the textural parameters were observed between adenocarcinoma and squamous cell carcinoma for homogeneity, energy, inertia, and correlation. The use of contrast media during scanning resulted in significant differences in homogeneity, energy, entropy, and inertia for adenocarcinoma but not squamous cell carcinoma. There was also a significant difference in all textural parameters between pathological T status for ypT0-ypT2 and ypT3-ypT4 adenocarcinomas, but not in squamous cell carcinoma patients. No additional value was found from using PET image data to aid segmentation of CT images.

Long-term weight development after esophagectomy for cancer-comparison between open Ivor-Lewis and minimally invasive surgical approaches.

Esophagectomy is an extensive procedure with severe postoperative effects. It can be assumed that the greater the trauma, the longer the nutritional recovery. This retrospective observational single-center cohort study compared weight development after esophagectomy with open and minimally invasive techniques. Three groups were compared in this study, one representing the first 41 patients who underwent the minimally invasive McKeown esophagectomy (MIMK). The second group included the first 84 consecutive patients operated with the minimally invasive Ivor-Lewis esophagectomy (MIIL). The third group comprised 100 consecutive patients operated with open thoracoabdominal Ivor-Lewis esophagectomy (IL). Virtually all patients submitted to a minimally invasive esophagectomy (MIE) and the majority with an IL had a jejunal catheter inserted during operation for postoperative enteral feeding. All together 225 patients were included in this study. The mean weight loss during the first year was 13.1% (±4.1), 11.2% (±6.1), and 9.6% (±7.5) in the IL, MIIL, and MIMK group, respectively (P = 0.85 and P = 0.95, respectively). The median duration of postoperative enteral nutrition support varied substantially within the groups and was 23.5 days in the IL group (range: 0-2033 days), 54.5 days in those having an MIIL (range: 0-308 days; P ≤ 0.001) and 57.0 days among patients in the MIMK group (range: 0-538 days; P ≤ 0.022). There was no difference in the risk of losing at least 10% of the preoperative weight at 3 or 6 months postoperatively between the groups. However, in patients who suffered severe complications (Clavien-Dindo score ≥ IIIb) after MIIL, there was a nonsignificant trend toward a lower risk of a 10% or greater weight loss, 3 months postoperatively. In conclusion, the greater surgical trauma associated with the traditional open esophagectomy was not followed by more severe weight loss, or other signs of poorer nutritional recovery, when compared to minimal invasive surgical techniques.

North European comparison of treatment strategy and survival in older patients with resectable gastric cancer: A EURECCA upper gastrointestinal group analysis.

BACKGROUND: As older gastric cancer patients are often excluded from randomized clinical trials, the most appropriate treatment strategy for these patients remains unclear. The current study aimed to gain more insight in treatment strategies and relative survival of older patients with resectable gastric cancer across Europe. METHODS: Population-based cohorts from Belgium, Denmark, The Netherlands, Norway, and Sweden were combined. Patients ≥70 years with resectable gastric cancer (cT1-4a, cN0-2, cM0), diagnosed between 2004 and 2014 were included. Resection rates, administration of chemotherapy (irrespective of surgery), and relative survival within a country according to stage were determined. RESULTS: Overall, 6698 patients were included. The percentage of operated patients was highest in Belgium and lowest in Sweden for both stage II (74% versus 56%) and stage III disease (57% versus 25%). For stage III, chemotherapy administration was highest in Belgium (44%) and lowest in Sweden (2%). Three year relative survival for stage I, II, and III disease in Belgium was 67.8% (95% CI:62.8-72.6), 41.2% (95% CI:37.3-45.2), 17.8% (95% CI:12.5-24.0), compared with 56.7% (95% CI:51.5-61.7), 31.3% (95% CI:27.6-35.2), 8.2% (95% CI:4.4-13.4) in Sweden. There were no significant differences in treatment strategies of patients with stage I disease. CONCLUSION: Substantial treatment differences are observed across North European countries for patients with stages II and III resectable gastric cancer aged 70 years or older. In the present comparison, treatment strategies with a higher proportion of patients undergoing surgery seemed to be associated with higher survival rates for patients with stages II or III disease.

Single center consecutive series cohort study of minimally invasive versus open resection for cancer in the esophagus or gastroesophageal junction.

Minimally invasive esophagectomy (MIE) has been introduced at many centers worldwide as evidence is accumulating that it reduces the risk of postoperative morbidity and mortality and decreases the length of hospital stay compared to conventional open esophagectomy. The study is a single institution cohort study of 366 consecutive patients treated with curative intent for cancer in the esophagus or gastroesophageal junction, comparing MIE to open surgery. The outcomes studied were peroperative bleeding, operation time, lymph node yield, complications, length of stay and overall survival. The results showed that MIE was associated with reduced peroperative bleeding and operation time. The patients in the MIE group had a statistically significant reduced risk of postoperative complications, 60.2% compared to 78.8% in the open group. In the MIE group 28.4% of the patients had postoperative complications classified according to the Clavien-Dindo classification system as grade IIIb-V compared to 38.2% in the open group, P = 0.046. Median hospital stay was reduced with 10 days comparing MIE to open surgery, P < 0.001. Mean number of resected lymph nodes was 31 in the MIE group and 22 in the open group (P < 0.001), while the R0 resections were 91.5% versus 85% (P = 0.057). Overall long-term survival was higher in the MIE group, a difference that however did not reach statistical significance (adjusted hazard ratio for three-year survival 0.76, 95% CI 0.54-1.08). In conclusion, MIE at a high volume center with a devoted specialist team reduces the risk of peroperative bleeding, operation time, and severe postoperative complications compared to open surgery for esophageal or junctional cancer. The number of resected lymph nodes was increased and the R0 resections were similar between the groups indicating a good oncological quality of the surgery.

Long-term functional outcomes after replacement of the esophagus with gastric, colonic, or jejunal conduits: a systematic literature review.

It is generally recognized that in patients with an intact stomach diagnosed with esophageal cancer, gastric tubulization and pull-up shall always be the preferred technique for reconstruction after an esophageal resection. However, in cases with extensive gastroesophageal junction (GEJ) cancer with aboral spread and after previous gastric surgery, alternative methods for reconstruction have to be pursued. Moreover, in benign cases as well as in those with early neoplastic lesions of the esophagus and the GEJ that are associated with long survival, it is basically unclear which conduit should be recommended. The aim of this study is to determine the long-term functional outcomes of different conduits used for esophageal replacement, based on a comprehensive literature review. Eligible were all clinical studies reporting outcomes after esophagectomy, which contained information on at least three years of follow-up after the operation in patients who were older than 18 years of age at the time of the operation. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic web-based search using MEDLINE, the Cochrane Library, and EMBASE databases was performed, reviewing medical literature published between January 2006 and December 2015. The scientific quality of the data was generally low, which allowed us to incorporate only 16 full text articles for the final analyses. After a gastric pull-up, the proportion of patients who suffered from dysphagia varied substantially but seemed to decrease over time with a mild dysphagia remaining during long-term follow-up. When reflux-related symptoms and complications were addressed, roughly two third of patients experienced mild to moderate reflux symptoms a long time after the resection. Following an isoperistaltic colonic graft, the functional long-term outcomes regarding swallowing difficulties were sparsely reported, while three studies reported reflux/regurgitation symptoms in the range of 5% to 16%, one of which reported the symptom severity as being mild. Only one report was available after the use of a long jejunal segment, which contained only six patients, who scored the severity of dysphagia and reflux as mild. Very few if any data were available on a structured assessment of dumping and disturbed bowel functions. Few high-quality data are available on the long-term functional outcomes after esophageal replacement irrespective of the use of a gastric tube, the right or left colon or a long jejunal segment. No firm conclusions regarding the advantages of one graft over the other can presently be drawn.

Outcomes following the main treatment options in patients with a leaking esophagus: a systematic literature review.

Leakage from the esophagus and gastroesophageal junction can be lethal due to uncontrolled contamination of the mediastinum. The most predominant risk factors for the subsequent clinical outcome are the patients' delay as well as the delay of diagnosis. Two major therapeutic concepts have been advocated: either prompt closure of the leakage by insertion of a self-expandable metal stent (SEMS) or more traditionally, surgical exploration. The objective of this review is to carefully scrutinize the recent literature and assess the outcomes of these two therapeutic alternatives in the management of iatrogenic perforation-spontaneous esophageal rupture as separated from those with anastomotic leak. A systematic web-based search using PubMed and the Cochrane Library was performed, reviewing literature published between January 2005 and December 2015. Eligible studies included all studies that presented data on the outcome of SEMS or surgical exploration in case of esophageal leak (including >3 patients). Only patients older than 15 years of age by the time of admission were included. Articles in other languages but English were excluded. Treatment failure was defined as a need for change in therapeutic strategy due to uncontrolled sepsis and mediastinitis, which usually meant rescue esophagectomy with end esophagostomy, death occurring as a consequence of the leakage or development of an esophagorespiratory fistula and/or other serious life threatening complications. Accordingly, the corresponding success rate is composed of cases where none of the failures above occurred. Regarding SEMS treatment, 201 articles were found, of which 48 were deemed relevant and of these, 17 articles were further analyzed. As for surgical management, 785 articles were retrieved, of which 82 were considered relevant, and 17 were included in the final analysis. It was not possible to specifically extract detailed clinical outcomes in sufficient numbers, when we tried to separately analyze the data in relation to the cause of the leakage: i.e. iatrogenic perforation-spontaneous esophageal rupture and anastomotic leak. As for SEMS treatment, originally 154 reports focused on iatrogenic perforation, 116 focused on spontaneous ruptures, and only four described the outcome following trauma and foreign body management. Only five studies used a prospective protocol to assess treatment efficacy. Regarding a leaking anastomosis, 80 reports contained information about the outcome after treatment of esophagogastrostomies and 35 reported the clinical course after an esophagojejunostomy. An overall success rate of 88% was reported among the 371 SEMS-treated patients, where adequate data were available, with a reported in hospital mortality amounting to 7.5%. Regarding the surgical exploration strategy, the vast majority of patients had an attempt to repair the defect by direct or enforced suturing. This surgical approach also included procedures such as patching with pleura or with a diaphragmatic flap. The overall reported success rate was 83% (305/368) and the in-hospital mortality was 17% (61/368). The current literature suggests that a SEMS-based therapy can be successfully applied as an alternative therapeutic strategy in esophageal perforation rupture.

Systematic review and meta-analysis on the significance of salvage esophagectomy for persistent or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy.

The therapeutic strategy to be recommended in case of recurrent or persistent squamous cell esophageal cancer after completed definitive chemoradiotherapy (dCRT) has to be documented. Salvage esophagectomy has traditionally been recognized as a viable option, but many clinicians oppose the use of surgery due to the associated excessive morbidity and mortality. 'Second-line' chemoradiotherapy (CRT) without surgery may offer a treatment alternative in these difficult and demanding clinical situations. Until now, no comprehensive attempt has been carried out to compare the respective therapeutic options. A systematic literature search was performed focusing on studies comparing survival and treatment-related mortality in patients submitted to salvage esophagectomy or second-line CRT for recurrent or persistent esophageal squamous cell carcinoma after dCRT. Hazard ratios and risk ratios were calculated to compare the effect of these therapeutic strategies on overall survival and treatment-related mortality, respectively. Four studies containing 219 patients, with persistent or recurrent esophageal squamous cell carcinoma after dCRT, were included in the meta-analysis. The analysis revealed an overall survival benefit following salvage esophagectomy with a pooled hazard ratio for death of 0.42 (95% confidence interval 0.21-0.86, P = 0.017) compared with second-line CRT. A treatment-related mortality of 10.3% was recorded in the 36 patients who were submitted to salvage esophagectomy, while it was impossible to perform a meta-analysis comparing treatment-related mortality between the groups. Salvage esophagectomy offers significant gain in long-term survival compared with second-line CRT, although the surgery is potentially at a price of a high treatment-related mortality.

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.

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.

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

BACKGROUND: 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. METHODS: MEDLINE, the Cochrane Library and Embase were searched to capture the incidence of any postoperative complications, cardiac complications, respiratory complications, anastomotic leakage, postoperative 30-day mortality, total postoperative mortality and treatment-related mortality in randomized clinical trials comparing NAC or NACR with surgery alone, or NAC versus NACR. Meta-analyses comparing NAC and NACR were conducted by using adjusted indirect comparison. RESULTS: Twenty-three relevant studies were identified. Comparing NAC or NACR with surgery alone, there was no increase in morbidity or mortality attributable to neoadjuvant therapy. Subgroup analysis of NACR for squamous cell carcinoma (SCC) suggested an increased risk of total postoperative mortality and treatment-related mortality compared with surgery alone: risk ratio 1·95 (95 per cent confidence interval 1·06 to 3·60; P = 0·032) and 1·97 (1·07 to 3·64; P = 0·030) respectively. A combination of direct comparison and adjusted indirect comparison showed no difference between NACR and NAC regarding morbidity or mortality. CONCLUSION: Neither NAC nor NACR for oesophageal carcinoma increases the risk of postoperative morbidity or perioperative mortality compared with surgery alone. There was no clear difference between NAC and NACR. Care should be taken with NACR in oesophageal SCC, where an increased risk of postoperative mortality and treatment-related mortality was apparent.

Surgical prevention of reflux after esophagectomy for cancer.

BACKGROUND: Reflux frequently occurs after a gastric conduit has replaced the resected esophagus. In this Swedish population-based cohort study, the potential antireflux effects of using cervical anastomosis, intrathoracic antireflux anastomosis, or pyloric drainage, and a risk of dysphagia due to cervical anastomosis and intrathoracic antireflux anastomosis were studied. METHODS: Patients undergoing esophagectomy with gastric conduit reconstruction in 2001-2005 were included. Reflux symptoms and dysphagia were assessed 6 months and 3 years postoperatively using a validated questionnaire (EORTC QLQ-OES18). The study exposures were cervical anastomosis, antireflux anastomosis, and pyloric drainage procedure. Multivariable logistic regression and propensity-adjusted analyses based on multinomial logistic regression estimated odds ratios (OR) with 95 % confidence intervals (CI), adjusted for potential confounding. RESULTS: A total of 304 patients were included in the study. Adjusted ORs for reflux symptoms were 0.9 (95 % CI 0.3-2.2) for patients with a cervical anastomosis compared to patients with an intrathoracic anastomosis, 0.9 (95 % CI 0.4-2.0) for patients with an antireflux anastomosis versus patients with a conventional anastomosis, and 1.5 (95 % CI 0.9-2.6) for patients after pyloric drainage versus patients without such a pyloric drainage procedure. Dysphagia was not statistically significantly increased after cervical anastomosis or antireflux anastomosis. ORs were virtually similar 3 years after surgery. No interactions were identified. The propensity analyses rendered similar results as the logistic regression models, except for a possibly increased dysphagia with a cervical anastomosis. CONCLUSIONS: Cervical anastomosis, antireflux anastomosis, and pyloric drainage do not seem to prevent reflux symptoms 6 months or 3 years after esophagectomy for cancer with a gastric conduit.

Surgical complications and long-term survival after esophagectomy for cancer in a nationwide Swedish cohort study.

AIMS: Acute surgical complications after esophageal resection for cancer may decrease the long-term survival. Previous results on this topic are conflicting and no population-based studies are available. METHODS: A prospective, nationwide Swedish study was conducted in 2001-2010. Eligible patients comprised those afflicted by esophageal or cardia cancer and underwent surgical resection in Sweden in 2001-2005. Details concerning patient and tumor characteristics, surgical procedures, and postoperative surgical complications were collected prospectively. Follow-up for mortality, starting from 90 days after the surgery, was done until May 2010. Cox proportional-hazards regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for age, tumor stage, sex, histology, comorbidity, surgical approach and surgical radicality. RESULTS: Among 567 included patients who survived at least 90 days postoperatively, 130 (22.9%) sustained a predefined surgical complication within 30 days of surgery. The adjusted HR of mortality was increased in patients who sustained surgical complications, compared to patients without such complications (HR 1.29, 95% CI 1.02-1.63). CONCLUSIONS: The occurrence of surgical complications might be an independent predictor for poorer long-term survival in patients resected for esophageal cancer, even in patients who survived the postoperative period.