Patient-reported outcomes after oesophagectomy in the multicentre LASER study.

BACKGROUND: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. METHODS: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. RESULTS: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. CONCLUSION: A long-term symptom burden is common after oesophageal cancer surgery.

The additive value of restaging-CT during neoadjuvant chemotherapy for gastric cancer.

INTRODUCTION: Computed tomography (CT) is used for restaging of gastric cancer patients during neoadjuvant chemotherapy (NAC). The treatment strategy could be altered after detection of distant interval metastases, possibly leading to a reduction in unnecessary chemotherapy cycles, its related toxicity, and surgical procedures. The aim of this study was to evaluate the additive value of restaging-CT during NAC in guiding clinical decision making in gastric cancer. MATERIALS AND METHODS: This retrospective, multicenter cohort study identified all patients with surgically resectable gastric adenocarcinoma (cT1-4a-x, N0-3-x, M0-x), who started NAC with curative intent. Restaging-CT was performed after 2 out of 3 cycles of NAC. The primary outcome was treatment alterations made based on restaging-CT by a multidisciplinary tumor board. Confirmation of metastases was obtained by surgery or biopsy. RESULTS: Between 2007 and 2015, CT-restaging was performed in 122 out of 152 included patients and timed after 2 cycles (n = 76) or after 3 cycles (n = 46) of NAC. Restaging-CT revealed a metastasis in 1 out of 122 restaged patients (1%) after which surgical resection was omitted, whereas 4 patients (3%) with distant interval metastases were not identified by restaging-CT and underwent a futile laparotomy. In 5 out of 76 patients (7%) disease progression was detected while undergoing NAC, leading to omission of the 3rd cycle of chemotherapy. CONCLUSION: The additive value of restaging-CT during NAC in gastric cancer is limited in guiding clinical decision making and therefore not recommended. Further studies may identify subgroups that may benefit of alternative diagnostic modalities.

Do esophageal cancer survivors work after esophagectomy and do health problems impact their work? A cross-sectional study.

PURPOSE: This study aimed to evaluate the occupational status and work impediments due to health problems in long-term esophageal cancer survivors. METHODS: The Short-Form Health and Labour Questionnaire (SF-HLQ) was sent to esophageal cancer survivors. Primary outcomes included the number of working esophageal cancer survivors and the patient-reported impact of health problems on work, as evaluated by the SF-HLQ. Patient and treatment characteristics were compared between survivors who worked and survivors who did not work at the time of follow-up after esophagectomy. RESULTS: The SF-HLQ was sent to 98 survivors and was completed by 86 of them. Of the 86 included survivors, 35 worked at the time of cancer diagnosis and 18 worked at a median follow-up of 48 months [range 23-87] after treatment. Survivors who worked at the time of follow-up were younger at the time of treatment when compared to survivors who had quit working after their cancer diagnosis (58.4 vs. 64.2 years, P = 0.006). Working survivors most commonly reported reduced work pace (44%), a self-imposed need to work in seclusion (33%), and concentration problems (28%) due to health problems at work. The majority of working survivors (93%) reported an efficiency score ≥ 8 on a scale from 1 (lowest efficiency) to 10 (highest efficiency). CONCLUSIONS: Nearly half of the esophageal cancer survivors who worked at the time of diagnosis also worked at a median follow-up of 48 months after esophagectomy. Despite health problems impacting work, most esophageal cancer survivors reported high efficiency at work. IMPLICATIONS FOR CANCER SURVIVORS: Esophageal cancer survivors can often work with high efficiency, despite potential health problems.

Prophylactic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer-A Systematic Review.

Survival after potentially curative treatment of gastric cancer remains low, mostly due to peritoneal recurrence. This descriptive review gives an overview of available comparative studies concerning prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with neither clinically evident metastases nor positive peritoneal cytology who undergo potentially curative gastrectomy. After searching the PubMed, Embase, CDSR, CENTRAL and ASCO meeting library, a total of 11 studies were included comparing surgery plus prophylactic HIPEC versus surgery alone (SA): three randomised controlled trials and eight non-randomised comparative studies, involving 1145 patients. Risk of bias was high in most of the studies. Morbidity after prophylactic HIPEC was 17-60% compared to 25-43% after SA. Overall survival was 32-35 months after prophylactic HIPEC and 22-28 months after SA. The 5-year survival rates were 39-87% after prophylactic HIPEC and 17-61% after SA, which was statistically significant in three studies. Peritoneal recurrence occurred in 7-27% in the HIPEC group, compared to 14-45% after SA. This review tends to demonstrate that prophylactic HIPEC for gastric cancer can be performed safely, may prevent peritoneal recurrence and may prolong survival. However, studies were heterogeneous and outdated, which emphasizes the need for well-designed trials conducted according to current standards.

Resection of hepatic and pulmonary metastasis from metastatic esophageal and gastric cancer: a nationwide study.

The standard of care for gastroesophageal cancer patients with hepatic or pulmonary metastases is best supportive care or palliative chemotherapy. Occasionally, patients can be selected for curative treatment instead. This study aimed to evaluate patients who underwent a resection of hepatic or pulmonary metastasis with curative intent. The Dutch national registry for histo- and cytopathology was used to identify these patients. Data were retrieved from the individual patient files. Kaplan-Meier survival analysis was performed. Between 1991 and 2016, 32,057 patients received a gastrectomy or esophagectomy for gastroesophageal cancer in the Netherlands. Of these patients, 34 selected patients received a resection of hepatic metastasis (n = 19) or pulmonary metastasis (n = 15) in 21 different hospitals. Only 4 patients received neoadjuvant therapy before metastasectomy. The majority of patients had solitary, metachronous metastases. After metastasectomy, grade 3 (Clavien-Dindo) complications occurred in 7 patients and mortality in 1 patient. After resection of hepatic metastases, the median potential follow-up time was 54 months. Median overall survival (OS) was 28 months and the 1-, 3-, and 5- year OS was 84%, 41%, and 31%, respectively. After pulmonary metastases resection, the median potential follow-up time was 80 months. The median OS was not reached and the 1-, 3-, and 5- year OS was 67%, 53%, and 53%, respectively. In selected patients with gastroesophageal cancer with hepatic or pulmonary metastases, metastasectomy was performed with limited morbidity and mortality and offered a 5-year OS of 31-53%. Further prospective studies are required.

Introduction of minimally invasive surgery for distal and total gastrectomy: a population-based study.

BACKGROUND: Minimally invasive gastrectomy has been introduced in Western populations during the last decade. As minimally invasive distal gastrectomy (MIDG) versus total gastrectomy (MITG) are procedures with a different complexity, outcomes may differ. The aim of this population-based cohort study was to evaluate the safety of MIDG and MITG. MATERIALS AND METHODS: All patients who underwent potentially curative gastrectomy for gastric adenocarcinoma were included from the Dutch Upper GI Cancer Audit (2011-2016). Propensity score matching was applied to create comparable groups of patients receiving open distal gastrectomy (ODG) versus MIDG and open total gastrectomy (OTG) versus MITG, using patient and tumor characteristics. Postoperative outcomes and short-term oncological outcomes were appraised. RESULTS: Of the 1970 eligible patients, 1138 underwent distal gastrectomy and 832 underwent total gastrectomy. For distal gastrectomy, 390 ODG were matched to 288 MIDG patients. Although overall postoperative morbidity and mortality were similar, patients who underwent MIDG encountered less intra-abdominal abscesses (4% vs. 1%, p = 0.039) and wound complications (6% vs. 2%, p = 0.021). The median hospital stay was shorter after MIDGs (9 vs. 7 days, p < 0.001). For total gastrectomy, 323 OTG patients were matched to 258 MITG patients. Overall postoperative morbidity, mortality and hospital stay were similar, whereas the anastomotic leakage rate was higher after MITGs (11% vs. 17%, p = 0.030). Short-term oncological outcomes between both groups were equal for distal and total gastrectomy. CONCLUSION: Benefits of MIG during the early introduction were demonstrated for distal gastrectomy but not for total gastrectomy. An increased anastomotic leakage rate was encountered for MITG.

Timing of postoperative chemotherapy in patients undergoing perioperative chemotherapy and gastrectomy for gastric cancer.

BACKGROUND: For patients who qualify for perioperative chemotherapy and gastrectomy for gastric cancer, the optimal timing of the postoperative chemotherapy (PC) seems equivocal. The aim of this study was to evaluate the influence of timing of PC on overall survival (OS) in patients receiving perioperative chemotherapy. METHODS: Patients undergoing perioperative chemotherapy and gastrectomy with curative intent (2010-2014) were extracted from the nationwide population-based Netherlands Cancer Registry. Timing of PC was analyzed as a linear and categorical variable (<6 weeks, 6-8 weeks, and >8 weeks). Risk factors for a late start of PC (≥6 weeks), and the association between timing of PC and OS were assessed by multivariable regression analyses. RESULTS: Among 1066 patients who underwent perioperative chemotherapy and gastrectomy, 463 (43%) patients started PC. PC was administered within 6 weeks in 208 (45%) patients, within 6-8 weeks in 155 (33%) patients, and after 8 weeks in 100 (22%) patients. A total of 419 (91%) and 351 (76%) patients finished all cycles of preoperative and PC, respectively. A late start of PC was associated with a longer hospital stay (+1 hospital day: OR 1.15, 95% CI [1.08-1.23], p < 0.001). Timing of PC was not associated with OS (6-8 weeks vs. <6 weeks, HR 1.14, 95% CI [0.79-1.65], p = 0.471; >8 weeks vs. <6 weeks, HR 1.04, 95% CI [0.79-1.65], p = 0.872). CONCLUSION: Timing of postoperative chemotherapy does not influence survival in patients receiving perioperative chemotherapy for gastric cancer. The results suggest that the early postoperative period may be safely used for recovery and optimizing patients for the start of PC.

Evaluation of PET and laparoscopy in STagIng advanced gastric cancer: a multicenter prospective study (PLASTIC-study).

BACKGROUND: Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3-4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) and staging laparoscopy (SL) may have a role in staging, but evidence is scarce. The aim of this study is to evaluate the impact and cost-effectiveness of PET and SL in addition to initial staging in patients with locally advanced gastric cancer. METHODS: This prospective observational cohort study will include all patients with a surgically resectable, advanced gastric adenocarcinoma (cT3-4b, N0-3, M0), that are scheduled for treatment with curative intent after initial staging with gastroscopy and CT. The modalities to be investigated in this study is the addition of PET and SL. The primary outcome of this study is the proportion of patients in whom the PET or SL lead to a change in treatment strategy. Secondary outcome parameters are: diagnostic performance, morbidity and mortality, quality of life, and cost-effectiveness of these additional diagnostic modalities. The study recently started in August 2017 with a duration of 36 months. At least 239 patients need to be included in this study to demonstrate that the diagnostic modalities are break-even. Based on the annual number of gastrectomies in the participating centers, it is estimated that approximately 543 patients are included in this study. DISCUSSION: In this study, it is hypothesized that performing PET and SL for locally advanced gastric adenocarcinomas results in a change of treatment strategy in 27% of patients and an annual cost-reduction in the Netherlands of €916.438 in this patient group by reducing futile treatment. The results of this study may be applicable to all countries with comparable treatment algorithms and health care systems. TRIAL REGISTRATION: NCT03208621 . This trial was registered prospectively on June 30, 2017.

Weekday of gastrectomy for cancer in relation to mortality and oncological outcomes - A Dutch population-based cohort study.

BACKGROUND: Some studies demonstrate that high-complex surgeries performed later in the week are associated with higher postoperative mortality and worse long-term survival. The aim of this cohort study was to determine whether weekday influences outcomes in patients undergoing gastrectomy for cancer. METHODS: All patients who underwent a curative gastrectomy for cancer (2006-2014) were selected from the nationwide population-based Netherlands Cancer Registry. Weekday was analyzed as categorized (Monday-Tuesday versus Wednesday-Friday) and discrete variable (Monday-Friday). The influence of weekday on postoperative 30- and 90-day mortality, and oncological outcomes (lymph node yield, radicality rate and overall survival) was assessed with multivariable logistic and Cox regression analyses. RESULTS: A total of 3.776 patients were included with a median overall survival of 26.7 months [range 0-120]. The 30- and 90-day mortality were 5% and 8% respectively, median lymph node yield was 13 [range 0-87], and radicality rate was 87%. In multivariable analysis, no influence of weekday was found on postoperative mortality (p > 0.05), on R0 resection rates (p > 0.05), nor on overall survival (Monday-Friday, HR 1.03, 95%CI 1.01-1.04, p = 0.111; Wednesday-Friday vs. Monday-Tuesday, HR 1.05, 95%CI 0.96-1.14, p = 0.307). The lymph node yield was significantly lower later in the week compared to earlier (Monday-Friday, OR 0.94, 95%CI 0.89-0.99, p = 0.013; Wednesday-Friday vs. Monday-Tuesday OR 0.83, 95%CI 0.71-0.96, p = 0.010), which was most apparent in recent years of surgery. CONCLUSION: Gastric cancer surgery can be performed safely throughout the week regarding postoperative mortality, radicality and overall survival. A point of concern is a reduced lymph node yield later in the week.

Association Between Waiting Time from Diagnosis to Treatment and Survival in Patients with Curable Gastric Cancer: A Population-Based Study in the Netherlands.

BACKGROUND: In the Netherlands, a maximum waiting time from diagnosis to treatment (WT) of 5 weeks is recommended for curative cancer treatment. This study aimed to evaluate the association between WT and overall survival (OS) in patients undergoing gastrectomy for cancer. METHODS: This nationwide study included data from patients diagnosed with curable gastric adenocarcinoma between 2005 and 2014 from the Netherlands Cancer Registry. Patients were divided into two groups: patients who received neoadjuvant therapy followed by gastrectomy, or patients who underwent gastrectomy as primary surgery. WT was analyzed as a categorical (≤5 weeks [Reference], 5-8 weeks, >8 weeks) and as a discrete variable. Multivariable Cox regression analysis was used to assess the influence of WT on OS. RESULTS: Among 3778 patients, 1701 received neoadjuvant chemotherapy followed by gastrectomy, and 2077 underwent primary gastrectomy. In the neoadjuvant group, median WT to neoadjuvant treatment was 4.6 weeks (interquartile range [IQR] 3.4-6.0), and median OS was 32 months. In the surgery group, median WT to surgery was 6.0 weeks (IQR 4.3-8.4), and median OS was 25 months. For both groups, WT did not influence OS (neoadjuvant: 5-8 weeks, hazard ratio [HR] 0.82, p = 0.068; >8 weeks, HR 0.85, p = 0.354; each additional week WT, HR 0.96, p = 0.078; surgery: 5-8 weeks, HR 0.91, p = 0.175; >8 weeks, HR 0.92, p = 0.314; each additional week WT, HR 0.99, p = 0.264). CONCLUSIONS: Longer WT until the start of curative treatment for gastric cancer is not associated with worse OS. These results could help to put WT into perspective as indicator of quality of care and reassure patients with gastric cancer.

Safety and feasibility of minimally invasive gastrectomy during the early introduction in the Netherlands: short-term oncological outcomes comparable to open gastrectomy.

BACKGROUND: Minimally invasive techniques for gastric cancer surgery have recently been introduced in the Netherlands, based on a proctoring program. The aim of this population-based cohort study was to evaluate the short-term oncological outcomes of minimally invasive gastrectomy (MIG) during its introduction in the Netherlands. METHODS: The Netherlands Cancer Registry identified all patients with gastric adenocarcinoma who underwent gastrectomy with curative intent between 2010 and 2014. Multivariable analysis was performed to compare MIG and open gastrectomy (OG) on lymph node yield (≥15), R0 resection rate, and 1-year overall survival. The pooled learning curve per center of MIG was evaluated by groups of five subsequent procedures. RESULTS: Between 2010 and 2014, a total of 277 (14%) patients underwent MIG and 1633 (86%) patients underwent OG. During this period, the use of MIG and neoadjuvant chemotherapy increased from 4% to 39% (p < 0.001) and from 47% to 62% (p < 0.001), respectively. The median lymph node yield increased from 12 to 20 (p < 0.001), and the R0 resection rate remained stable, from 86% to 91% (p = 0.080). MIG and OG had a comparable lymph node yield (OR, 1.01; 95% CI, 0.75-1.36), R0 resection rate (OR, 0.86; 95% CI, 0.54-1.37), and 1-year overall survival (HR, 0.99; 95% CI, 0.75-1.32). A pooled learning curve of ten procedures was demonstrated for MIG, after which the conversion rate (13%-2%; p = 0.001) and lymph node yield were at a desired level (18-21; p = 0.045). CONCLUSION: With a proctoring program, the introduction of minimally invasive gastrectomy in Western countries is feasible and can be performed safely.

Robot-assisted minimally invasive esophagectomy.

Esophagolymphadenectomy is the cornerstone of multimodality treatment for resectable esophageal cancer. The preferred surgical approach is transthoracic, with a two-field lymph node dissection and gastric conduit reconstruction. A minimally invasive approach has been shown to reduce postoperative complications and increase quality of life. Robot-assisted minimally invasive esophagectomy (RAMIE) was developed to facilitate this complex thoracoscopic procedure. RAMIE has been shown to be safe with good oncologic results and reduced morbidity. The use of RAMIE opens new indications for curative surgery in patients with T4b tumors, high mediastinal tumors, and lymph node metastases after neoadjuvant treatment.

[Robot-assisted minimally invasive esophagectomy. German version]. / Roboterassistierte minimal-invasive Ösophagektomie.

Esophagolymphadenectomy is the cornerstone of multimodality treatment for resectable esophageal cancer. The preferred surgical approach is transthoracic, with a two-field lymph node dissection and gastric conduit reconstruction. A minimally invasive approach has been shown to reduce postoperative complications and increase quality of life. Robot-assisted minimally invasive esophagectomy (RAMIE) was developed to facilitate this complex thoracoscopic procedure. RAMIE has been shown to be safe with good oncologic results and reduced morbidity. The use of RAMIE opens new indications for curative surgery in patients with T4b tumors, high mediastinal tumors, and lymph node metastases after neoadjuvant treatment.