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.

Quality of life and symptom assessment in paraesophageal hernias: a systematic literature review of reporting standards.

BACKGROUND: Paraesophageal hernias (PEH) present with a range of symptoms affecting physical and mental health. This systematic review aims to assess the quality of reporting standards for patients with PEH, identify the most frequently used quality of life (QOL) and symptom severity assessment tools in PEH and to ascertain additional symptoms reported by these patients not captured by these tools. METHODS: A systematic literature review according to PRISMA protocols was carried out following a literature search of MEDLINE, Embase and Cochrane databases for studies published between January 1960 and May 2020. Published abstracts from conference proceedings were included. Data on QOL tools used and reported symptoms were extracted. RESULTS: This review included 220 studies reporting on 28 353 patients. A total of 46 different QOL and symptom severity tools were used across all studies, and 89 different symptoms were reported. The most frequently utilized QOL tool was the Gastro-Esophageal Reflux Disease-Health related quality of life questionnaire symptom severity instrument (47.7%), 57.2% of studies utilized more than 2 QOL tools and 'dysphagia' was the most frequently reported symptom, in 55.0% of studies. Notably, respiratory and cardiovascular symptoms, although less common than GI symptoms, were reported and included 'dyspnea' reported in 35 studies (15.9%). CONCLUSIONS: There lacks a QOL assessment tool that captures the range of symptoms associated with PEH. Reporting standards for this cohort must be improved to compare patient outcomes before and after surgery. Further investigations must seek to develop a PEH specific tool, that encompasses the relative importance of symptoms when considering surgical intervention and assessing symptomatic improvement following surgery.

Global burden of oesophageal and gastric cancer by histology and subsite in 2018.

OBJECTIVES: To provide updated estimates of the global burden of oesophageal and gastric cancer by subsite and type. METHODS: Using data from population-based cancer registries, proportions of oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC) out of all oesophageal as well as cardia gastric cancer (CGC) and non-CGC (NCGC) out of all gastric cancer cases were computed by country, sex and age group. Proportions were subsequently applied to the estimated numbers of oesophageal and gastric cancer cases from GLOBOCAN 2018. Age-standardised incidence rates (ASR) were calculated. RESULTS: In 2018, there were an estimated 572 000 new cases of oesophageal cancer worldwide, 85 000 OACs (ASR 0.9 per 100 000, both sexes combined) and 482 000 OSCCs (ASR 5.3). Out of 1.03 million gastric cancers, there were an estimated 181 000 cases of CGC (ASR 2.0) and 853 000 cases of NCGC (ASR 9.2). While the highest incidence rates of OSCC, CGC and NCGC were observed in Eastern Asia (ASRs 11.1, 4.4 and 17.9, respectively), rates of OAC were highest in Northern Europe (ASR 3.5). While globally OSCC and NCGC remain the most common types of oesophageal and gastric cancer, respectively, rates of OAC exceed those of OSCC in an increasing number of high-income countries. CONCLUSIONS: These updated estimates of the global burden of oesophageal and gastric cancer by subtype and site suggest an ongoing transition in epidemiological patterns. This work will serve as a cornerstone for policy-making and will aid in developing appropriate cancer control strategies.

18F-FDG PET-CT after Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients to Optimize Surgical Decision Making.

BACKGROUND: Prognosis of esophageal cancer patients can be significantly improved by neoadjuvant chemoradiotherapy (nCRT). Given the aggressive nature of esophageal tumors, it is conceivable that in a significant portion of patients treated with nCRT, dissemination already becomes manifest during the period of nCRT. The aim of this retrospective study was to determine the value and diagnostic accuracy of PET-CT after neoadjuvant chemoradiotherapy to identify patients with metastases preoperatively in order to prevent non-curative surgery. METHODS: From January 2011 until February 2013 esophageal cancer patients deemed eligible for a curative approach with nCRT and surgical resection underwent a PET-CT after completion of nCRT. If abnormalities on PET-CT were suspected metastases, histological proof was acquired. A clinical decision model was designed to assess the cost-effectiveness of this diagnostic strategy. RESULTS: 156 patients underwent a PET-CT after nCRT. In 31 patients (19.9%) PET-CT showed abnormalities suspicious for dissemination, resulting in 17 cases of proven metastases (10.9%). Of the patients without proven metastases 133 patients were operated. In 6 of these 133 cases distant metastases were detected intraoperatively, corresponding to 4.5% false-negative results. The standard introduction of a post-neoadjuvant therapy PET-CT led to a reduction of overall health care costs per patient compared to a scenario without restaging with PET-CT ($34,088 vs. $36,490). CONCLUSION: In 10.9% of esophageal cancer patients distant metastases were detected by standard PET-CT after neoadjuvant chemoradiotherapy. To avoid non-curative resections we advocate post-neoadjuvant therapy PET-CT as a cost-effective step in the standard work-up of candidates for surgery.

The effect of on-demand vs deep neuromuscular relaxation on rating of surgical and anaesthesiologic conditions in patients undergoing thoracolaparoscopic esophagectomy (DEPTH trial): study protocol for a randomized controlled trial.

BACKGROUND: Deep muscle relaxation has been shown to facilitate operating conditions during laparoscopic surgery. Minimally invasive esophageal surgery is a high-risk procedure in which the use of deep neuromuscular block (NMB) may improve conditions in the thoracic phase as well. Neuromuscular antagonists can be given on demand or by continuous infusion (deep NMB). However, the positioning of the patient often hampers train-of-four (TOF) monitoring. A continuous infusion thus may result in a deep NMB at the end of surgery. The use of neostigmine not only is insufficient for reversing deep NMB but also may be contraindicated for this procedure because of its cholinergic effects. Sugammadex is an effective alternative but is rather expensive. This study aims to evaluate the use of deep versus on-demand NMB on operating, anaesthesiologic conditions, and costs in patients undergoing a two- or three-phase thoracolaparoscopic esophageal resection. METHODS/DESIGN: We will conduct a single-center randomized controlled double-blinded intervention study. Sixty-six patients undergoing a thoracolaparoscopic esophageal resection will be included. Patients will receive either continuous infusion of rocuronium 0.6 mg/kg per hour (group 1) or continuous infusion of NaCl 0.9 % 0.06 ml/kg per hour (group 2). In both groups, on-demand boluses of rocuronium can be given (open-label design). The primary aim of this study is to compare the surgical rating scale (SRS) during the abdominal phase. Main secondary aims are to evaluate SRS during the thoracic phase, to evaluate anesthesiologic conditions, and to compare costs (in euros) associated with use of rocuronium, sugammadex, and duration of surgery. DISCUSSION: This study is the first to evaluate the benefits of deep neuromuscular relaxation on surgical and anaesthesiologic conditions during thoracolaparoscopic esophageal surgery. This surgical procedure is unique because it consists of both an abdominal phase and a thoracic phase taking place in different order depending on the subtype of surgery (a two- or three-stage transthoracic esophagectomy). In addition, possible benefits associated with deep NMB, such as decrease in operating time, will be weighed against costs. TRIAL REGISTRATION: European Clinical Trials Database (EudraCT) number: 2014-002147-18 (obtained 19 May 2014) ClinicalTrials.gov: NCT02320734 (obtained 18 Dec. 2014).

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.

Laparoscopic surgery for gastro-esophageal acid reflux disease.

Gastro-esophageal reflux disease is a troublesome disease for many patients, severely affecting their quality of life. Choice of treatment depends on a combination of patient characteristics and preferences, esophageal motility and damage of reflux, symptom severity and symptom correlation to acid reflux and physician preferences. Success of treatment depends on tailoring treatment modalities to the individual patient and adequate selection of treatment choice. PubMed, Embase, The Cochrane Database of Systematic Reviews, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched for systematic reviews with an abstract, publication date within the last five years, in humans only, on key terms (laparosc* OR laparoscopy*) AND (fundoplication OR reflux* OR GORD OR GERD OR nissen OR toupet) NOT (achal* OR pediat*). Last search was performed on July 23nd and in total 54 articles were evaluated as relevant from this search. The laparoscopic Toupet fundoplication is the therapy of choice for normal-weight GERD patients qualifying for laparoscopic surgery. No better pharmaceutical, endoluminal or surgical alternatives are present to date. No firm conclusion can be stated on its cost-effectiveness. Results have to be awaited comparing the laparoscopic 180-degree anterior fundoplication with the Toupet fundoplication to be a possible better surgical alternative. Division of the short gastric vessels is not to be recommended, nor is the use of a bougie or a mesh in the vast majority of GERD patients undergoing surgery. The use of a robot is not recommended. Anti-reflux surgery is to be considered expert surgery, but there is no clear consensus what is to be called an 'expert surgeon'. As for setting, ambulatory settings seem promising although high-level evidence is lacking.

Postoperative information needs and communication barriers of esophageal cancer patients.

OBJECTIVE: Given the poor prognosis of esophageal cancer and the impact of surgery on health-related quality of life (HRQL), addressing patients' postoperative information needs is important. This study aimed to examine (1) the content and type of patients' information needs and (2) patient perceived facilitators and barriers to patient participation. METHODS: Interviews were conducted with 20 purposefully selected esophageal cancer patients. Open and structured questions were alternated. The transcribed interviews were analysed inductively and deductively, using MAXqda. RESULTS: Patients' post-operative information needs concerned HRQL, medical care and prognosis, covering several sub-domains. Different types of needs were identified, e.g., requests for information about cause, course and self-management. Barriers to patient participation mostly reflected beliefs and skills, and could be categorized into agenda and communication barriers. Facilitators of patient participation reflected physician, patient and interaction characteristics, companion support and pre-visit preparation. Many patients saw merit in pre-visit preparation interventions; few endorsed skill-building interventions. CONCLUSION: This study listed the postoperative information needs of esophageal cancer patients. Moreover, it gained insight into patient-perceived barriers and facilitators of patient participation. PRACTICE IMPLICATIONS: The findings demonstrate what information physicians should have available and informs interventions to support patients in meeting their information needs.

[Laparoscopic surgery for inflammatory bowel disease; an update]. / Laparoscopische chirurgie voor inflammatoire darmziekten: een update.

OBJECTIVE: To carry out a review of the literature for the short- and long-term effects of various laparoscopic operations in the inflammatory bowel diseases ulcerative colitis and Crohn's disease and to compare these operations with open surgical procedures. DESIGN: Review of the literature. METHOD: PubMed (Medline), Embase and Cochrane databases were searched for randomised clinical trials and meta-analyses on this topic, published between January 1991 and August 2008. If no level A1, A2 or A2B studies were found, we searched for the best available evidence. RESULTS: For Crohn's disease, there was level A2 evidence that, in comparison with open surgery, in experienced hands laparoscopic ileocaecal resection enhanced recovery and led to a shorter hospital stay and lower costs. Following laparoscopic surgery, subjective body image and cosmetic appearance scores were higher, when compared in the long term. In patients with ulcerative colitis, the expected benefits of laparoscopic proctocolectomy have not yet been demonstrated in a randomised study. Although there was a trend towards a reduced hospital stay (1.6 days) when laparoscopy proctocolectomy was performed, the operating time was 1.5 h longer than in conventional surgery. Body image and cosmetic appearance scores were also higher here when compared in the long term. CONCLUSION: Laparoscopic ileocaecal resection is preferable in Crohn's disease, provided that it is performed in a centre with sufficient expertise in laparoscopic surgery. In patients with ulcerative colitis, laparoscopic proctocolectomy with construction of an ileoanal pouch is indicated in young active patients who are concerned for their appearance. Given its complexity, this operation should be performed only in specialist centres.

Diagnostic strategies for pre-treatment staging of patients with oesophageal cancer.

BACKGROUND/AIMS: Current guidelines for staging oesophageal cancer recommend a series of preoperative investigations. There is no consensus on the recommended order for these investigations or whether all investigations are necessary in all patients. Our aim was to determine an efficient strategy for pre-treatment staging of patients with oesophageal cancer. METHODS: We retrospectively compared 15 staging strategies, based on all possible orders of all possible subsets of three staging modalities (computed tomography, endoscopic ultrasonography and external ultrasonography of the neck). We assumed that if distant metastases or local irresectability were found and confirmed, no further investigations would be performed. Main outcome was the minimal number of investigations needed to detect all patients with incurable disease. RESULTS: Using all three investigations in all 412 patients would lead to performance of 1,236 investigations. Both strategies starting with computed tomography or endoscopic ultrasonography and ending with external ultrasonography were most efficient, using a total of 1,112 investigations. CONCLUSION: The use of a conditional staging strategy with a specific order of imaging can reduce the number of tests necessary to identify incurable patients with oesophageal cancer by 10%. In our opinion, this is not enough to recommend implementation of a logistically more complex diagnostic system.

NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial).

BACKGROUND: Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer. METHODS/DESIGN: Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score).Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy). DISCUSSION: The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice. TRIAL REGISTRATION: ISRCTN45750457.

Value of bronchoscopy after EUS in the preoperative assessment of patients with esophageal cancer at or above the carina.

INTRODUCTION: Esophageal cancer is an aggressive disease with a strong tendency to infiltrate into surrounding structures. The aim of the present study is to determine the additional value of bronchoscopy for detecting invasion of the tracheobronchial tree after endoscopic ultrasonography (EUS) in the preoperative assessment of patients with esophageal cancer at or above the carina. MATERIALS AND METHODS: Between January 1997 and December 2006, 104 patients were analyzed for histologically proven esophageal cancer at or above the carina. All patients underwent both EUS and bronchoscopy (with biopsy on indication) in the preoperative assessment of local resectability. RESULTS AND DISCUSSION: After extensive diagnostic workup, 58 of 104 patients (56%) were eligible for potentially curative esophagectomy; nine of these 58 patients (9/58, 15%) appeared to be incurable peroperatively because of ingrowth in the tracheobronchial tree (five patients), ingrowth in other vital structures (two patients) or distant metastases (two patients). Of the 46 non-operable patients, local irresectability (T-stage 4) was identified in 26 patients (26/46, 57%) due to invasion of vital structures on EUS: invasion of the aorta in six patients, invasion of the lung in 11 patients; in 12 patients invasion of the tracheobronchial tree was described, which was confirmed by bronchoscopy in only five patients. No patients with T4 were identified by bronchoscopy alone. CONCLUSION: For patients with esophageal tumors at or above the carina, no additional value of bronchoscopy (with biopsy on indication) to exclude invasion of the tracheobronchial tree was seen after EUS in a specialized centre. Although based on relatively small numbers, we conclude that bronchoscopy is not indicated if no invasion of the airways is identified on EUS.

Medical liability insurance claims on entry-related complications in laparoscopy.

BACKGROUND: Installation of the pneumoperitoneum is an essential part of laparoscopic surgery. Creation can be performed by either the open or a closed technique. The aim of this study was to assess the number of and contributing factors to entry-related complications in medical liability insurance claims in The Netherlands. METHODS: A retrospective chart review was performed, including all malpractice claims filed at MediRisk, which is presently the largest medical liability mutual insurance company for institutions, mainly hospitals, in healthcare in The Netherlands. RESULTS: From January 1993 to December 2005, 41 claims were identified as entry-related complications which comprised 18% of all laparoscopy-related complications leading to claims. Most were young (median age = 35 years) female patients who had routine, nonadvanced, laparoscopic procedures planned as short-stay or day-care procedures. The claims were equally divided between general surgery (n = 20) and gynecology (n = 21). A total of 51 structures were injured. There were 18 vascular structure injuries, 30 bowel injuries, and three other injuries. An open entry technique was used in only two (5%) patients. Vascular injury was exclusively associated with closed entry. In only 19 (46%) patients the entry-related complication was diagnosed peroperatively, consisting of 70% of the vascular and 25% of the bowel injuries. Twenty-six patients (64%) were admitted to the intensive care unit for a median of five days. There was no mortality. Besides conversion, the majority of the patients filed a claim to compensate for a longer hospital stay and related costs. A payment was made in 17 (57%) of the 30 settled claims. CONCLUSIONS: Medical liability claims concerning laparoscopic entry-related complications comprised a fifth of all laparoscopy-related claims. Claims concerning entry-related complications occurred in young patients who had routine, nonadvanced procedures. In the investigated cases most claims involved the closed-entry technique.

Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial).

BACKGROUND: Recent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay. The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease. METHODS/DESIGN: The LAFA-trial is a double blinded, multicenter trial with a 2 x 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate. Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected. DISCUSSION: The LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease.