Multimodal Therapy Versus Primary Surgery for Gastric and Gastroesophageal Junction Diffuse Type Carcinoma, with a Focus on Signet Ring Cell Carcinoma: A Nationwide Study.

BACKGROUND: Diffuse type adenocarcinoma and, more specifically, signet ring cell carcinoma (SRCC) of the stomach and gastroesophageal junction (GEJ) have a poor prognosis and the value of neoadjuvant chemo(radio)therapy (nCRT) is unclear. METHODS: All patients who underwent surgery for diffuse type gastric and GEJ carcinoma between 2004 and 2015 were retrospectively included from the Netherlands Cancer Registry. The primary outcome was overall survival after surgery. Kaplan-Meier curves were plotted. Furthermore, multivariable Poisson and Cox regressions were performed, correcting for confounders. To comply with the Cox regression proportional hazard assumption, gastric cancer survival was split into two groups, i.e. <90 days and >90 days, postoperatively by adding an interaction variable. RESULTS: Analyses included 2046 patients with diffuse type cancer: 1728 gastric cancers (50% SRCC) and 318 GEJ cancers (39% SRCC). In the gastric cancer group, 49% received neoadjuvant chemotherapy (nCT) and 51% received primary surgery (PS). All-cause mortality within 90 days postoperatively was lower after nCT (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.20-0.44; p < 0.001). Also after 90 days, mortality was lower in the nCT group (HR for the interaction variable 2.84, 95% CI 1.87-4.30, p < 0.001; total HR 0.29*2.84 = 0.84). In the GEJ group, 38% received nCT, 22% received nCRT, and 39% received PS. All-cause mortality was lower after nCT (HR 0.63, 95% CI 0.43-0.93; p = 0.020) compared with PS. The nCRT group was removed from the Cox regression analysis since the Kaplan-Meier curves of nCRT and PS intersected. The results for gastric and GEJ carcinomas were similar between the SRCC and non-SRCC subgroups. CONCLUSION: For gastric and GEJ diffuse type cancer, including SRCC, nCT was associated with increased survival.

The association between hospital variation in curative treatment for esophagogastric cancer and health-related quality of life and survival.

BACKGROUND: As previous studies showed significant hospital variation in curative treatment of esophagogastric cancer, this study assesses the association between this variation and overall, cancer-specific and recurrence-free survival, and Health-Related Quality of Life (HRQoL). METHODS: Patients diagnosed with potentially curable esophageal or gastric cancer between 2015 and 2018 as registered in the Netherlands Cancer Registry were included. Data on overall survival was available for all patients, data on cancer-specific and recurrence-free survival and HRQoL was available for subgroups. Patients were classified according to diagnosis in hospitals with low, medium or high probability of treatment with curative intent (LP, MP or HP). Multivariable models were used to assess the association between LP, MP and HP hospitals and HRQoL and survival. RESULTS: This study includes 7,199 patients with esophageal, and 2,407 with gastric cancer. Overall and cancer-specific survival was better for patients diagnosed in HP versus LP hospitals for both esophageal (HR = 0.82, 95%CI:0.77-0.88 and HR = 0.82, 95%CI:0.75-0.91, respectively), and gastric cancer (HR = 0.82, 95%CI:0.73-0.92 and HR = 0.74, 95%CI:0.64-0.87, respectively). These differences disappeared after adjustments for treatment. Recurrence-free survival was worse for gastric cancer patients diagnosed in HP hospitals (HR = 1.50, 95%CI:1.14-1.96), which disappeared after adjustment for radicality of surgery. Minor, but no clinically relevant, differences in HRQoL were observed. CONCLUSIONS: Patients diagnosed in hospitals with a high probability of treatment with curative intent have a better overall and cancer-specific but not recurrence-free survival, while minor differences in HRQoL were observed.

Hospital practice variation in the proportion of patients with esophagogastric cancer discussed during an expert multidisciplinary team meeting.

BACKGROUND: Multidisciplinary team meetings (MDTM) and especially MDTMs in which expert centres are involved (expert MDTMs) are a key element in adequate cancer care. However, variation among hospitals in the proportion of patients presented during an expert MDTM has been described. This study aims to investigate national practice variation in the proportion of patients with oesophageal or gastric cancer being discussed during an expert MDTM. METHODS: Patients diagnosed with oesophageal or gastric cancer in 2018-2019 were selected from the Netherlands Cancer Registry (n = 6,921). Multilevel logistic regression analyses were used to analyse the association between patient, and tumour characteristics, and the probability to be discussed in an expert MDTM. Variation was analysed according to the hospital and region of diagnosis for: all patients, patients with a potentially curable (cT1-4A cTX, any cN, cM0) or incurable tumour stage (cT4b and/or cM1). RESULTS: In total, 79% of patients were discussed during an expert MDTM, of whom 84% (n = 3,424) and 71% (n = 2,018) with potentially curable, or incurable oesophageal or gastric cancer, respectively. The proportion of patients discussed during an expert MDTM ranged from 54% to 98%, and 17% to 100% between hospitals for potentially curable and incurable patients, respectively (all p < 0.0001). Adjusted analyses showed significant hospital (all p < 0.0001), but no regional variation regarding the patients discussed during an expert MDTM. CONCLUSION: For patients with oesophageal or gastric cancer the probability of being discussed during an expert MDTM varies considerably according to the hospital of diagnosis.

Treatment decision-making during outpatient clinic visit of patients with esophagogastric cancer. The perspectives of clinicians and patients, a mixed method, multiple case study.

BACKGROUND: The probability of undergoing treatment with curative intent according to the hospital of diagnosis varies for esophagogastric cancer in the Netherlands. Little is known about the factors contributing to this variation. This study aimed to improve the understanding of the differences between the multidisciplinary team meeting treatment proposal and the treatment that was actually carried out and to qualitatively investigate the differences in treatment decision-making after the multidisciplinary team meeting treatment proposal between hospitals. METHODS: To gain an in-depth understanding of treatment decision-making, quantitative data (i.e., multidisciplinary team meeting proposal and treatment that was carried out) were collected from the Netherlands Cancer Registry. Changes in the multidisciplinary team meeting proposal and applied treatment comprised changes in the type of treatment option (i.e., curative or palliative, or no change) and were calculated according to the multivariable multilevel probability of undergoing treatment with curative intent (low, middle, and high). Qualitative data were collected from eight hospitals, including observations of 26 outpatient clinic consultations, 30 in-depth interviews with clinicians, seven focus groups with clinicians, and three focus groups with patients. Clinicians and patients' perspectives were assessed using thematic content analysis. RESULTS: The multidisciplinary team meeting proposal and applied treatment were concordant in 97% of the cases. Clinicians' implementation of treatment decision-making in clinical practice varied, which was mentioned by the clinicians to be due to the clinician's personality and values. Differences between clinicians consisted of discussing all treatment options versus only the best fitting treatment option and the extent of discussing the benefits and harms. Most patients aimed to undergo curative treatment regardless of the consequences, since they believed this could prolong their life. CONCLUSION: Since changes in the multidisciplinary team meeting-proposed treatment and actual treatment were rarely observed, this study emphasizes the importance of an adequately formulated multidisciplinary team meeting proposal.

Refraining from resection in patients with potentially curable gastric carcinoma.

BACKGROUND: Surgical resection is the cornerstone of curative treatment for gastric cancer. The aim of this study was to evaluate reasons for and patient- and tumor characteristics that are associated with refraining from surgical resection in patients with potentially curable gastric cancer. MATERIALS AND METHODS: Between 2015 and 2017, all patients with potentially curable gastric adenocarcinoma (cT1-4a-x, cN0-3-x, cM0) were included from the Netherlands Cancer Registry (NCR). Patients were divided into a resection (RG) and a no-resection group (nRG). Reasons for not undergoing resection as registered by the NCR were evaluated. Using multivariable logistic regression analyses, patient and tumor characteristics associated with refraining from resection were assessed. RESULTS: Of the 1679 analyzed patients with potentially curable disease, 1127 patients (67%) underwent resection, and 552 patients (33%) did not. Most common registered reasons for refraining from surgery were patient refusal (25%), low performance status (23%), comorbidity and extent of disease (both 10%). Factors associated with not undergoing resection were: age ≥80 years (OR 4.77, [95%CI 2.27-10.06], p < 0.001), low Social-Economic-Status (SES) (OR 2.68 [95%CI 1.31-5.46], p = 0.007), WHO performance status 3-4 (OR 10.48 [95%CI 2.41-45.73], p = 0.002) with several accompanying comorbidities, unclassified Lauren classification (OR 3.93 [95%CI 1.61-9.56], p = 0.003) and overlapping/diffuse tumors (OR 3.51, [95%CI 1.54-8.05], p = 0.003). CONCLUSION: A third of patients with potentially curable gastric cancer did not undergo resection. Most frequent registered reasons for refraining from surgery were patient refusal, performance status, comorbidity and extent of disease. Additionally, multivariable analyses identified higher age, lower SES, and poor tumor characteristics as associated factors.

Changes in hospital variation in the probability of receiving treatment with curative intent for esophageal and gastric cancer.

BACKGROUND: Previous studies describe a large variation in the proportion of patients undergoing treatment with curative intent for esophageal (EC) and gastric cancer (GC). Since centralization of surgical care was initiated and more awareness regarding hospital practice variation was potentially present, we hypothesized that hospital practice variation for potentially curable EC and GC patients changed over time. METHODS: Patients with potentially curable EC (n = 10,115) or GC (n = 3988) diagnosed between 2012-2017 were selected from the Netherlands Cancer Registry. Multilevel multivariable logistic regression was used to analyze the differences in the probability of treatment with curative intent between hospitals of diagnosis over time, comparing 2012-2014 with 2015-2017. Relative survival (RS) between hospitals with different probabilities of treatment with curative intent were compared. RESULTS: The range of proportions of patients undergoing treatment with curative intent per hospital of diagnosis for EC was 45-95 % in 2012-2014 and 54-89 % in 2015-2017, and for GC 52-100 % and 45-100 %. The adjusted variation declined for EC with Odds Ratios ranging from 0.50 to 1.72 between centers in the first period to 0.70-1.44 in the second period (p < 0.001) and did not change for GC (Odds Ratios ranging from 0.78 to 1.23 to 0.82-1.23, (p = 1.00)). A higher probability of treatment with curative intent was associated with a better survival for both malignancies. CONCLUSION: Although substantial variation between hospitals of diagnosis in the probability in receiving treatment with curative intent still exists for both malignancies, it has decreased for EC. A low probability of receiving curative treatment remained associated with worse survival.

Implementation of a regional video multidisciplinary team meeting is associated with an improved prognosis for patients with oesophageal cancer A mixed methods approach.

BACKGROUND: Studies have shown that multidisciplinary team meetings (MDTM) improve diagnostic work-up and treatment-decisions. This study aims to evaluate the influence of implementing a regional-video-Upper-GI-MDTM (uMDTM) for oesophageal cancer (OC) on the number of patients discussed, treatment-decisions, perspectives of involved clinicians and overall survival (OS) in the Eindhoven Upper-GI Network consisting of 1 resection hospital and 5 referring hospitals. METHODS: Between 2012 and 2018, patients diagnosed with OC within this region, were selected from the Netherlands Cancer Registry(n = 1119). From 2014, an uMDTM was gradually implemented and a mixed-method quantitative and qualitative design was used to analyse changes. Quantitative outcomes were described before and after implementation of the uMDTM. Clinicians were interviewed to assess their perspectives regarding the uMDTM. RESULTS: After participation in the uMDTM more patients were discussed in an MDTM (80%-89%,p < 0.0001) and involvement of a resection centre during the uMDTM increased (43%-82%,p < 0.0001). The proportion of patients diagnosed with potentially curable OC (cT1-4a-x, any cN, cM0) remained stable (59%-61%, p = 0.452). Endoscopic or surgical resections were performed more often (28%-34%,p = 0.034) and the use of best supportive care decreased (21%-15%,p = 0.018). In the qualitative part an improved knowledge, collaboration and discussion was perceived due to implementation of the uMDTM. Three-year OS for all OC patients increased after the implementation of the uMDTM (24%-30%,p = 0.025). CONCLUSIONS: Implementation of a regional Upper-GI MDTM was associated with an increase in patients discussed with a resection centre, more curative resections and a better OS. It remains to be elucidated which factors in the clinical pathway explain this observed improved survival.

A population-based study on intestinal and diffuse type adenocarcinoma of the oesophagus and stomach in the Netherlands between 1989 and 2015.

AIM: To investigate the nationwide time trends in incidence and survival of oesophageal and gastric adenocarcinomas according to the Laurén classification (intestinal, diffuse and mixed type). METHODS: All patients diagnosed in the Netherlands with oesophageal or gastric adenocarcinoma between 1989 and 2015 were included. A syntax was developed to determine the histological subtype based on pathology reports as archived in the Dutch pathology registry. These reports were linked to individual data from the Netherlands Cancer Registry. Relative survival was used to assess survival. RESULTS: The histological subtype could be determined in 18.691 (84.1%) oesophageal and in 32.312 (83.5%) gastric adenocarcinomas. Among these, 79% were intestinal and 21% diffuse type in oesophageal cancers, compared to 55% intestinal and 44% diffuse type in gastric cancers. Relative median survival of intestinal type tumours was longer than that of diffuse type tumours, that is, 12.1 versus 9.4 months for oesophageal carcinomas, and 10.1 versus 7.6 months for gastric carcinomas, respectively. Between 1989 and 2015, the relative median survival of non-metastatic intestinal and diffuse type oesophageal adenocarcinoma improved from 12.0 to 30.0 months, and from 12.0 to 19.2 months, respectively. The same was true for intestinal type gastric carcinoma (from 22.8 to 27.6 months) but for diffuse type gastric carcinoma, the increase was less (from 16.8 to 18.0 months). CONCLUSION: In this nationwide study, histological subtypes of oesophageal and gastric adenocarcinomas differed in incidence and survival times. These findings may call for a differentiated treatment approach.

The Importance of the Microbiome in Bariatric Surgery: a Systematic Review.

Bariatric surgery results in sustained weight loss, improvement of metabolic and hormonal changes, and reduction of comorbidities in obese patients. However, beneficial effects of bariatric surgery are not solely explained by restriction and malabsorption induced by surgery itself. Changes in the microbiome might play a role in this mechanism. A systematic review was performed in which 21 studies were included. The microbiome was affected by surgery and profound changes occurred in the first year of follow-up. An increase in Bacteroides and Proteobacteria and a decrease in Firmicutes were observed postoperatively in most studies. These changes were associated with weight loss. Bariatric surgery induces profound changes in the microbiome. This may be related to the beneficial effect of bariatric surgery on comorbidities associated with obesity.