Impact of 18FFDG-PET/CT and Laparoscopy in Staging of Locally Advanced Gastric Cancer: A Cost Analysis in the Prospective Multicenter PLASTIC-Study.

BACKGROUND: Unnecessary D2-gastrectomy and associated costs can be prevented after detecting non-curable gastric cancer, but impact of staging on treatment costs is unclear. This study determined the cost impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) and staging laparoscopy (SL) in gastric cancer staging. MATERIALS AND METHODS: In this cost analysis, four staging strategies were modeled in a decision tree: (1) 18FFDG-PET/CT first, then SL, (2) SL only, (3) 18FFDG-PET/CT only, and (4) neither SL nor 18FFDG-PET/CT. Costs were assessed on the basis of the prospective PLASTIC-study, which evaluated adding 18FFDG-PET/CT and SL to staging advanced gastric cancer (cT3-4 and/or cN+) in 18 Dutch hospitals. The Dutch Healthcare Authority provided 18FFDG-PET/CT unit costs. SL unit costs were calculated bottom-up. Gastrectomy-associated costs were collected with hospital claim data until 30 days postoperatively. Uncertainty was assessed in a probabilistic sensitivity analysis (1000 iterations). RESULTS: 18FFDG-PET/CT costs were €1104 including biopsy/cytology. Bottom-up calculations totaled €1537 per SL. D2-gastrectomy costs were €19,308. Total costs per patient were €18,137 for strategy 1, €17,079 for strategy 2, and €19,805 for strategy 3. If all patients undergo gastrectomy, total costs were €18,959 per patient (strategy 4). Performing SL only reduced costs by €1880 per patient. Adding 18FFDG-PET/CT to SL increased costs by €1058 per patient; IQR €870-1253 in the sensitivity analysis. CONCLUSIONS: For advanced gastric cancer, performing SL resulted in substantial cost savings by reducing unnecessary gastrectomies. In contrast, routine 18FFDG-PET/CT increased costs without substantially reducing unnecessary gastrectomies, and is not recommended due to limited impact with major costs. TRIAL REGISTRATION: NCT03208621. This trial was registered prospectively on 30-06-2017.

Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma in Eastern versus Western countries: meta-analysis.

OBJECTIVE: Locally advanced oesophageal squamous cell carcinoma can be treated with neoadjuvant chemoradiotherapy or chemotherapy followed by oesophagectomy. Discrepancies in pathological response rates have been reported between studies from Eastern versus Western countries. The aim of this study was to compare the pathological response to neoadjuvant chemoradiotherapy in Eastern versus Western countries. METHODS: Databases were searched until November 2022 for studies reporting pCR rates after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma. Multi-level meta-analyses were performed to pool pCR rates separately for cohorts from studies performed in centres in the Sinosphere (East) or in Europe and the Anglosphere (West). RESULTS: For neoadjuvant chemoradiotherapy, 51 Eastern cohorts (5636 patients) and 20 Western cohorts (3039 patients) were included. Studies from Eastern countries included more men, younger patients, more proximal tumours, and more cT4 and cN+ disease. Patients in the West were more often treated with high-dose radiotherapy, whereas patients in the East were more often treated with a platinum + fluoropyrimidine regimen. The pooled pCR rate after neoadjuvant chemoradiotherapy was 31.7% (95% c.i. 29.5% to 34.1%) in Eastern cohorts versus 40.4% (95% c.i. 35.0% to 45.9%) in Western cohorts (fixed-effect P = 0.003). For cohorts with similar cTNM stages, pooled pCR rates for the East and the West were 32.5% and 41.9% respectively (fixed-effect P = 0.003). CONCLUSION: The pathological response to neoadjuvant chemoradiotherapy is less favourable in patients treated in Eastern countries compared with Western countries. Despite efforts to investigate accounting factors, the discrepancy in pCR rate cannot be entirely explained by differences in patient, tumour, or treatment characteristics.

Development of a Reliable Surgical Quality Assurance System for 2-stage Esophagectomy in Randomized Controlled Trials.

OBJECTIVE: The aim was to develop a reliable surgical quality assurance system for 2-stage esophagectomy. This development was conducted during the pilot phase of the multicenter ROMIO trial, collaborating with international experts. SUMMARY OF BACKGROUND DATA: There is evidence that the quality of surgical performance in randomized controlled trials influences clinical outcomes, quality of lymphadenectomy and loco-regional recurrence. METHODS: Standardization of 2-stage esophagectomy was based on structured observations, semi-structured interviews, hierarchical task analysis, and a Delphi consensus process. This standardization provided the structure for the operation manual and video and photographic assessment tools. Reliability was examined using generalizability theory. RESULTS: Hierarchical task analysis for 2-stage esophagectomy comprised fifty-four steps. Consensus (75%) agreement was reached on thirty-nine steps, whereas fifteen steps had a majority decision. An operation manual and record were created. A thirty five-item video assessment tool was developed that assessed the process (safety and efficiency) and quality of the end product (anatomy exposed and lymphadenectomy performed) of the operation. The quality of the end product section was used as a twenty seven-item photographic assessment tool. Thirty-one videos and fifty-three photographic series were submitted from the ROMIO pilot phase for assessment. The overall G-coefficient for the video assessment tool was 0.744, and for the photographic assessment tool was 0.700. CONCLUSIONS: A reliable surgical quality assurance system for 2-stage esophagectomy has been developed for surgical oncology randomized controlled trials. ETHICAL APPROVAL: 11/NW/0895 and confirmed locally as appropriate, 12/SW/0161, 16/SW/0098.Trial registration number: ISRCTN59036820, ISRCTN10386621.

A single blinded randomized controlled trial comparing semi-mechanical with hand-sewn cervical anastomosis after esophagectomy for cancer (SHARE-study).

OBJECTIVE: The aim was to compare leak rate between hand-sewn end-to-end anastomosis (ETE) and semi-mechanical anastomosis (SMA) after esophagectomy with gastric tube reconstruction. BACKGROUND DATA: The optimal surgical technique for creation of an anastomosis in the neck after esophagectomy is unclear. METHODS: Patients with esophageal cancer undergoing esophagectomy with gastric tube reconstruction and cervical anastomosis were eligible for participation after written informed consent. Patients were randomized in 1:1 ratio. Primary endpoint was anastomotic leak rate defined as external drainage of saliva from the site of the anastomosis or intra-thoracic manifestation of leak. Secondary endpoints included anastomotic stricture rate at one year follow up, number of endoscopic dilatations, dysphagia-score, hospital stay, morbidity, and mortality. Patients were blinded for intervention. RESULTS: Between August 2011 and July 2014, 174 patients with esophageal cancer underwent esophagectomy. Ninety-three patients were randomized to ETE (n = 44) or SMA (n = 49). Anastomotic leak occurred in 9 of 44 patients (20%) in the ETE group and 12 of 49 patients (24%) in the SMA group (absolute difference 4%, 95% CI -13% to +21%; p = .804). There was no significant difference in dysphagia at 1 year postoperatively (ETE 25% vs. SMA 20%; p = .628), in stricture rate (ETE 25% vs. 19% in SMA, p = .46), nor in median hospital stay (17 days in the ETE group, 13 days in the SMA group), morbidity (82% vs. 73%, p = .460) or mortality (0% vs. 4%, p = .175) between the groups.

The Impact of Signet Ring Cell Differentiation on Outcome in Patients with Esophageal and Gastroesophageal Junction Adenocarcinoma.

BACKGROUND: Little is known about the association between signet ring cell (SRC) differentiation and response to neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal and junctional adenocarcinoma (EAC). We aimed to assess if SRC differentiation is associated with survival and response to nCT or nCRT in patients with EAC. METHODS: Patients who underwent nCT and nCRT followed by surgery for EAC from 2000 until 2016 were identified from two institutional prospectively maintained databases. The pretreatment biopsy report or surgical resection specimen was used to differentiate patients into an SRC or non-SRC group. RESULTS: Overall, 129 (19%) of 689 patients included had SRCs (nCT: n = 64; nCRT: n = 65). The SRC group had a more advanced ypT stage (p = 0.003), a higher number of positive lymph nodes in the resection specimen {median (interquartile range [IQR]) 2 [0-5] vs. 1 [0-3]; p = 0.002} and a higher rate of R1/R2 resections (19.4% vs. 12%; p = 0.026). SRC differentiation was not an independent prognostic factor for overall survival (OS) or disease-free survival (DFS). Following nCT, the SRC group had significantly shorter DFS (median [IQR] 12 [5-50] vs. 23 [8-164]; p = 0.013), but not OS, compared with the non-SRC group. In contrast, no differences according to SRC status for OS or DFS were found in patients who underwent nCRT. CONCLUSIONS: SRC differentiation was not independently associated with worse OS in patients with EAC who underwent neoadjuvant therapy and surgery. However, nCRT was associated with greater tumor downstaging and better DFS.

Impact of Extracapsular Lymph Node Involvement After Neoadjuvant Chemoradiation Therapy Followed by Surgery in Carcinoma of the Esophagus: A Multicenter Study.

OBJECTIVES: The current study aims to examine the impact of extracapsular lymph node involvement (EC-LNI) on survival for both esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) treated with neoadjuvant chemoradiation therapy (nCRT) followed by surgery. BACKGROUND: Studies have demonstrated the negative prognostic value of EC-LNI in primary surgery, but its impact after nCRT remains unclear. METHODS: From the databases of 6 European high-volume centers 1505 patients with R0 resections were withheld. Oncologic variables, including ypT, ypN, number of positive lymph nodes, and lymph node capsular status: EC-LNI and intracapsular lymph node involvement (IC-LNI), were examined. Statistical analysis was performed by Cox proportional hazards modeling. RESULTS: In SCC 182 patients (31.6%) had positive lymph nodes, of whom 60 (33.0%) showed EC-LNI. In AC 391 patients (42.1%) had positive lymph nodes, of whom 147 (37.6%) showed EC-LNI. Overall 5-year survival (O5YS) in SCC was 42.0%. Presence of EC-LNI meant a significantly worse O5YS than IC-LNI or pN0 (10.6%, 39.5%, and 47.4%, respectively; P < 0.05). O5YS in AC was 41.2%. No significant difference was observed between EC-LNI and IC-LNI (P = 0.322). In the multivariate analysis, among the examined possible prognosticators, presence of EC-LNI showed the highest hazard ratio (2.29, confidence interval: 1.52-3.47) as an independent prognosticator for overall survival in SCC, but it was not in AC. CONCLUSIONS: Based on this international multicenter study, the presence of EC-LNI after nCRT is at least as important as N-stage for survival and EC-LNI is the strongest prognosticator for overall survival in SCC but not in AC.

P53 and SOX2 Protein Expression Predicts Esophageal Adenocarcinoma in Response to Neoadjuvant Chemoradiotherapy.

OBJECTIVE: The aim of the study was to investigate the association between p53, SOX2, and CD44 protein expression and tumor response, and to validate potential predictive biomarker(s) in an independent cohort. BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery has become a standard of care for esophageal adenocarcinoma (EAC). However, the response to nCRT is highly variable among patients. METHODS: EAC patients who underwent nCRT and surgery, between January 2003 and December 2014 at the Erasmus University Medical Center, were included and divided into a primary (n = 77) and a validation cohort (n = 70). P53, SOX2, and CD44 expression was detected by immunohistochemistry in pretreatment tumor biopsies, and scored independently by 2 investigators. Response to nCRT was assessed based on tumor regression grade (TRG) in the resection specimen. RESULTS: Forty-one (53%) patients in the primary cohort and 33 (47%) patients in the validation cohort showed major response (TRG1 or TRG2) in the resection specimen. Aberrant p53 and absence of SOX2 were associated with major response in the primary cohort: adjusted odds ratio (OR) 6.3 [95% confidence interval (CI), 1.3-30.1) and adjusted OR 4.1 (95% CI, 1.4-12.4), respectively. The same was true for the validation cohort (p53: adjusted OR 8.6; 95% CI, 0.93-80.9 and SOX2: adjusted OR 6.1; 95% CI, 1.6-23.4). The highest probability of a major response was seen in patients with concurrent aberrant p53 and absence of SOX2 expression, with an OR of 6.7 (95% CI, 2.1-21.4) and 6.2 (95% CI, 1.8-21.2) in the primary and validation cohort. CONCLUSIONS: Pattern of p53 and particularly SOX2 protein expression in EAC predicts response to nCRT. These biomarkers may help to individualize treatment in EAC patients.

Using the Comprehensive Complication Index to Assess the Impact of Neoadjuvant Chemoradiotherapy on Complication Severity After Esophagectomy for Cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery for patients with esophageal or junctional cancer has become a standard of care. The comprehensive complication index (CCI) has recently been developed and accounts for all postoperative complications. Hence, CCI better reflects the burden of all combined postoperative complications in surgical patients than the Clavien-Dindo score alone, which incorporates only the most severe complication. This study was designed to evaluate the severity of complications in patients treated with nCRT followed by esophagectomy versus in patients who underwent esophagectomy alone using the comprehensive complication index. STUDY-DESIGN: All patients included in the CROSS trial-a randomized, clinical trial on the value of nCRT followed by esophagectomy-were included. Complications were assessed and graded using the Clavien-Dindo classification. CCI was derived from these scores, using the CCI calculator available online ( www.assessurgery.com ). CCI of patients who underwent nCRT followed by surgery was compared with the CCI of patients who underwent surgery alone. RESULTS: In both groups 161 patients were included. The median (and interquartile range) CCI of patients with nCRT and surgery was 26.22 (17.28-42.43) versus 25.74 (8.66-43.01) in patients who underwent surgery alone (p = 0.58). There also was no difference in CCI between subgroups of patients with anastomotic leakage, pulmonary complications, cardiac complications, thromboembolic events, chyle leakage, and wound infections. CONCLUSIONS: Neoadjuvant chemoradiotherapy according to CROSS did not have a negative impact on postoperative complication severity expressed by CCI compared with patients who underwent surgery alone for potentially curable esophageal or junctional cancer.

Laparoscopic versus open gastrectomy for gastric cancer, a multicenter prospectively randomized controlled trial (LOGICA-trial).

BACKGROUND: For gastric cancer patients, surgical resection with en-bloc lymphadenectomy is the cornerstone of curative treatment. Open gastrectomy has long been the preferred surgical approach worldwide. However, this procedure is associated with considerable morbidity. Several meta-analyses have shown an advantage in short-term outcomes of laparoscopic gastrectomy compared to open procedures, with similar oncologic outcomes. However, it remains unclear whether the results of these Asian studies can be extrapolated to the Western population. In this trial from the Netherlands, patients with resectable gastric cancer will be randomized to laparoscopic or open gastrectomy. METHODS: The study is a non-blinded, multicenter, prospectively randomized controlled superiority trial. Patients (≥18 years) with histologically proven, surgically resectable (cT1-4a, N0-3b, M0) gastric adenocarcinoma and European Clinical Oncology Group performance status 0, 1 or 2 are eligible to participate in the study after obtaining informed consent. Patients (n = 210) will be included in one of the ten participating Dutch centers and are randomized to either laparoscopic or open gastrectomy. The primary outcome is postoperative hospital stay (days). Secondary outcome parameters include postoperative morbidity and mortality, oncologic outcomes, readmissions, quality of life and cost-effectiveness. DISCUSSION: In this randomized controlled trial laparoscopic and open gastrectomy are compared in patients with resectable gastric cancer. It is expected that laparoscopic gastrectomy will result in a faster recovery of the patient and a shorter hospital stay. Secondly, it is expected that laparoscopic gastrectomy will be associated with a lower postoperative morbidity, less readmissions, higher cost-effectiveness, better postoperative quality of life, but with similar mortality and oncologic outcomes, compared to open gastrectomy. The study started on 1 December 2014. Inclusion and follow-up will take 3 and 5 years respectively. Short-term results will be analyzed and published after discharge of the last randomized patient. TRIAL REGISTRATION: NCT02248519.

Location of lymph node involvement in patients with esophageal adenocarcinoma predicts survival.

BACKGROUND: The location of positive lymph nodes has been abandoned in the seventh classification of the TNM staging system for esophageal adenocarcinoma. The present study evaluates whether distribution of involved nodes relative to the diaphragm in addition to TNM 7 further refines prediction. METHODS: Pathology reports of patients who underwent esophagectomy between 2000 and 2008 for adenocarcinoma of the esophagus were reviewed and staging was performed according to the seventh UICC-AJCC staging system. In addition, lymph node involvement of nodal stations above and below the diaphragm was investigated by endoscopic ultrasonography (EUS) in a separate cohort of patients who were scheduled for esophagectomy between 2008 and 2009 at two institutions. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed with a Cox regression model. RESULTS: Some 327 patients who had undergone esophagectomy for cancer were included. Multivariate analysis revealed that patients with from three to six involved lymph nodes in the resection specimen on both sides of the diaphragm had a twofold higher chance of dying compared to patients with the same number of involved lymph nodes on one side of the diaphragm. EUS assessment of lymph node metastases relative to the diaphragm in 102 patients showed that nodal involvement on both sides of the diaphragm was associated with worse survival than when nodes on one side or no nodes are involved [HR (95 % CI) 2.38 (1.15-4.90)]. CONCLUSIONS: A combined staging system that incorporates distribution of lymph nodes relative to the diaphragm refines prognostication after esophagectomy as assessed in the resected specimen and pretreatment as assessed by EUS. This improved staging has the potential to have a great impact on clinical decision making as to whether to embark upon potentially curative or palliative treatments.

Surgeon's steering behaviour towards patients to participate in a cluster randomised trial on active surveillance for oesophageal cancer: A qualitative study.

INTRODUCTION: Few studies have been conducted into how physicians use steering behaviour that may persuade patients to choose for a particular treatment, let alone to participate in a randomised trial. The aim of this study is to assess if and how surgeons use steering behaviour in their information provision to patients in their choice to participate in a stepped-wedge cluster randomised trial investigating an organ sparing treatment in (curable) oesophageal cancer (SANO trial). MATERIALS AND METHODS: A qualitative study was performed. Thematic content analysis was applied to audiotaped and transcribed consultations of twenty patients with eight different oncological surgeons in three Dutch hospitals. Patients could choose to participate in a clinical trial in which an experimental treatment of 'active surveillance' (AS) was offered. Patients who did not want to participate underwent standard treatment: neoadjuvant chemoradiotherapy followed by oesophagectomy. RESULTS: Surgeons used various techniques to steer patients towards one of the two options, mostly towards AS. The presentation of pros and cons of treatment options was imbalanced: positive framing of AS was used to steer patients towards the choice for AS, and negative framing of AS to make the choice for surgery more attractive. Further, steering language, i.e. suggestive language, was used, and surgeons seemed to use the timing of the introduction of the different treatment options, to put more focus on one of the treatment options. CONCLUSION: Awareness of steering behaviour can help to guide physicians in more objectively informing patients on participation in future clinical trials.

Esophageal cancer patients' need for information and support in making a treatment decision between standard surgery and active surveillance.

BACKGROUND: This study explores patients' need for information and support in deciding on esophageal cancer treatment, when experimental active surveillance and standard surgery are both feasible. METHODS: This psychological companion study was conducted alongside the Dutch SANO-trial (Surgery As Needed for Oesophageal cancer). In-depth interviews and questionnaires were used to collect data from patients who declined participation in the trial because they had a strong preference for either active surveillance (n = 20) or standard surgery (n = 20). Data were analyzed using both qualitative and quantitative techniques. RESULTS: Patients prefer to receive information directly from their doctors and predominantly rely on this information to make a treatment decision. Other information resources are largely used to confirm their treatment decision. Patients highly value support from their loved ones and appreciate emphatic doctors to actively involve them in the decision-making process. Overall, patients' needs for information and support during decision-making were met. CONCLUSIONS: The importance of shared decision-making and the role doctors have in this process is underlined. The role of doctors is essential at the initial phase of decision-making: Once patients seem to have formed their treatment preference for either active surveillance or surgery, the influence of external resources (including doctors) may be limited.

Comparison of the 6th and 7th Editions of the UICC-AJCC TNM Classification for Esophageal Cancer.

BACKGROUND: The new 7th edition of the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC) tumor, node, metastasis (TNM) staging system is the ratification of data-driven recommendations from the Worldwide Esophageal Cancer Collaboration database. Generalizability remains questionable for single institutions. The present study serves as a validation of the 7th edition of the TNM system in a prospective cohort of patients with predominantly adenocarcinomas from a single institution. METHODS: Included were patients who underwent transhiatal esophagectomy with curative intent between 1991 and 2008 for invasive carcinoma of the esophagus or gastroesophageal junction. Excluded were patients who had received neoadjuvant chemo(radio)therapy, patients after a noncurative resection and patients who died in the hospital. Tumors were staged according to both the 6th and the 7th editions of the UICC-AJCC staging systems. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed with a Cox regression model. The likelihood ratio chi-square test related to the Cox regression model and the Akaike information criterion were used for measuring goodness of fit. RESULTS: A study population of 358 patients was identified. All patients underwent transhiatal esophagectomy for adenocarcinoma. Overall 5-year survival rate was 38%. Univariate analysis revealed that pT stage, pN stage, and pM stage significantly predicted overall survival. Prediction was best for the 7th edition, stratifying for all substages. CONCLUSIONS: The application of the 7th UICC-AJCC staging system results in a better prognostic stratification of overall survival compared to the 6th edition. The fact that the 7th edition performs better predominantly in patients with adenocarcinomas who underwent a transhiatal surgical approach, in addition to findings from earlier research in other cohorts, supports its generalizability for different esophageal cancer practices.

Influence of young age on outcome after esophagectomy for cancer.

BACKGROUND: The incidence of esophageal cancer has risen among all age groups. Controversy exists about the clinical presentation and prognosis of young patients. The aim of this study was to compare the clinicopathologic characteristics and outcomes after surgery between patients with esophageal cancer who were <50 years of age and those ≥50 years of age. METHODS: Patients diagnosed with esophageal carcinoma who underwent esophagectomy between January 1990 and December 2010 in a single institution were selected from a prospective database. Patients aged <50 years at diagnosis (n = 163) were compared with those ≥50 years (n = 1151) with respect to clinicopathologic stage and oncologic outcome. RESULTS: Younger patients had less co-morbidity (p < 0.001). There were no significantly differences in tumor localization, histology, differentiation, or TNM stage in the two groups. In both groups, 37 % of the patients underwent neoadjuvant chemo(radio)therapy. One or more nonsurgical complications developed in 53 % of the older group versus 42 % in the younger group (p = 0.012). In-hospital mortality was 6.3 % for patients ≥50 years compared to 1.8 % for younger patients (p = 0.021). The 5 year overall survival was significantly better for the younger patients than for those ≥50 years (41 vs. 31 %, p < 0.001), but median disease-specific and disease-free survival did not differ between the groups (37 vs. 30 months, p = 0.140 and 49 vs. 28 months, p = 0.079, respectively). Multivariate analysis identified moderate, poorly, and undifferentiated tumors; tumor-positive resection margins (pR1-2); and TNM stage IIB-IV as independent predictors of disease-specific survival. CONCLUSIONS: A considerable proportion (12 %) of patients diagnosed with resectable esophageal carcinoma were <50 years. Phenotypic tumor characteristics and disease-specific survival were comparable for the two age groups.

Intrathoracic vs Cervical Anastomosis After Totally or Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer: A Randomized Clinical Trial.

Background: Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred location of the anastomosis after transthoracic MIE. Objective: To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial. Design, Setting, and Participants: This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020. Intervention: Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis. Main Outcomes and Measures: The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life. Results: Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, -19.4% [95% CI, -29.5% to -9.3%]). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, -21.9% [95% CI, -32.1% to -11.6%]). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, -11.3% [-20.4% to -2.2%]), lower incidence of recurrent laryngeal nerve palsy (risk difference, -7.3% [95% CI, -12.1% to -2.5%]), and better quality of life in 3 subdomains (mean differences: dysphagia, -12.2 [95% CI, -19.6 to -4.7]; problems of choking when swallowing, -10.3 [95% CI, -16.4 to 4.2]; trouble with talking, -15.3 [95% CI, -22.9 to -7.7]). Conclusions and Relevance: In this randomized clinical trial, intrathoracic anastomosis resulted in better outcome for patients treated with transthoracic MIE for midesophageal to distal esophageal or gastroesophageal junction cancer. Trial Registration: Trialregister.nl Identifier: NL4183 (NTR4333).

18F-Fludeoxyglucose-Positron Emission Tomography/Computed Tomography and Laparoscopy for Staging of Locally Advanced Gastric Cancer: A Multicenter Prospective Dutch Cohort Study (PLASTIC).

Importance: The optimal staging for gastric cancer remains a matter of debate. Objective: To evaluate the value of 18F-fludeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer. Design, Setting, and Participants: This multicenter prospective, observational cohort study included 394 patients with locally advanced, clinically curable gastric adenocarcinoma (≥cT3 and/or N+, M0 category based on CT) between August 1, 2017, and February 1, 2020. Exposures: All patients underwent an FDG-PET/CT and/or SL in addition to initial staging. Main Outcomes and Measures: The primary outcome was the number of patients in whom the intent of treatment changed based on the results of these 2 investigations. Secondary outcomes included diagnostic performance, number of incidental findings on FDG-PET/CT, morbidity and mortality after SL, and diagnostic delay. Results: Of the 394 patients included, 256 (65%) were men and mean (SD) age was 67.6 (10.7) years. A total of 382 patients underwent FDG-PET/CT and 357 underwent SL. Treatment intent changed from curative to palliative in 65 patients (16%) based on the additional FDG-PET/CT and SL findings. FDG-PET/CT detected distant metastases in 12 patients (3%), and SL detected peritoneal or locally nonresectable disease in 73 patients (19%), with an overlap of 7 patients (2%). FDG-PET/CT had a sensitivity of 33% (95% CI, 17%-53%) and specificity of 97% (95% CI, 94%-99%) in detecting distant metastases. Secondary findings on FDG/PET were found in 83 of 382 patients (22%), which led to additional examinations in 65 of 394 patients (16%). Staging laparoscopy resulted in a complication requiring reintervention in 3 patients (0.8%) without postoperative mortality. The mean (SD) diagnostic delay was 19 (14) days. Conclusions and Relevance: This study's findings suggest an apparently limited additional value of FDG-PET/CT; however, SL added considerably to the staging process of locally advanced gastric cancer by detection of peritoneal and nonresectable disease. Therefore, it may be useful to include SL in guidelines for staging advanced gastric cancer, but not FDG-PET/CT.

Preoperative and early postoperative quality of life predict survival in potentially curable patients with esophageal cancer.

BACKGROUND: In patients with esophageal cancer, evidence for prognostic significance of preoperative quality of life (QoL) is limited, while the prognostic significance of postoperative QoL has not been investigated at all. AIM: To determine whether preoperative and postoperative QoL measurements can predict survival independently from clinical and pathological factors, in patients with potentially curable esophageal adenocarcinoma. METHODS: A randomized controlled trial was performed from 1994 to 2000 in two academic medical centres, comparing transthoracic and transhiatal esophagectomy. QoL questionnaires were sent before and 3 months after surgery (Medical Outcome Study Short Form-20 and Rotterdam Symptom Checklist). Uni- and multivariate Cox regression analyses were used to examine firstly the prognostic value of preoperative QoL and several clinical factors, and secondly of postoperative QoL, several clinical factors, and pathological staging. RESULTS: Out of 220 randomized patients, 199 participated in the QoL-study. In the multivariate preoperative model physical symptom scale (p = 0.021), tumor length (p = 0.034), and endosonographic T-stage (p = 0.003) were predictive for overall survival. In the postoperative multivariate analysis, social functioning (p = 0.035), pain (p = 0.026), and activity level (p = 0.037) predicted survival, besides pathological T-stage (p < 0.001) and N-stage (p < 0.001). CONCLUSION: In the present paper the first large consecutive series of potentially curable esophageal cancer patients is presented in whom prospectively collected QoL data before and after potentially curative surgical resection were used to predict survival. Both preoperative (physical symptoms) and postoperative (social functioning, pain, and activity level) QoL subscales are independent predictors of survival in potentially curable patients with esophageal adenocarcinoma.

Functional changes after pancreatoduodenectomy: diagnosis and treatment.

Relatively little is known about the gastrointestinal function after recovery of a pancreatoduodenectomy. This review focuses on the functional changes of the stomach, duodenum and pancreas that occur after pancreatoduodenectomy. Although the mortality in relation to pancreatoduodenectomy has decreased over the years, it remains associated with considerable morbidity, which occurs in 40-60% of patients. Physical complaints early after the operation are often caused by motility disorders, in particular delayed gastric emptying, which occurs in up to 40% of patients. During longer follow-up of these patients the occurrence of endocrine and exocrine pancreatic insufficiency becomes more predominant. Diabetes mellitus develops in 20-50% of patients after a pancreatic resection (pancreatogenic diabetes). The main presenting symptoms of exocrine insufficiency are weight loss and steatorrhea. Its presence is suspected on clinical ground and can be supported by fecal elastase-1 measurement. Exocrine insufficiency can be compensated with oral enteric-coated enzyme supplements. The quality of life issue will be addressed as an important outcome measurement after pancreaticoduodenectomy. Furthermore, the functional changes after pancreatoduodenectomy are described in detail with suggestions for diagnosis and treatment.

Neoadjuvant chemoradiotherapy for esophageal cancer: a review of meta-analyses.

BACKGROUND: Most randomized controlled trials (RCTs) that have compared neoadjuvant chemoradiation followed by surgery with surgery alone for locally advanced esophageal cancer have shown no difference in survival between the two treatments. Meta-analyses on neoadjuvant chemoradiation in esophageal cancer, however, are discordant. METHODS: For the present study, published meta-analyses on neoadjuvant chemoradiation for esophageal cancer were identified from the PubMed database and critically appraised in order to make a judgment on the applicability of neoadjuvant chemoradiation in clinical practice and decision making. RESULTS: Two of the six meta-analyses examined did not show a significant survival benefit in patients with resectable esophageal cancer. Differences in the studies included and statistical methods applied might account for this. Moreover, there was heterogeneity between the RCTs included in the meta-analyses with regard to the patients included, tumor histology, and radiotherapy and chemotherapy regimes. Also, surgical technique was not uniform. No data on individual patients were available for most meta-analyses. The RCTs included in the meta-analyses were of inadequate sample size. All were started in the nineties, and hence methods for diagnosis, staging, treatment delivery, and outcome measurement reflect clinical practice during that decade. CONCLUSIONS: The current data on neoadjuvant chemoradiation for esophageal cancer strongly indicate the need for designing future high-quality trials that will contribute to a better understanding of the role of neoadjuvant treatment for resectable cancer of the esophagus and help to identify patient subgroups that would benefit most.