Gastric cancer often presents in a metastasized stage. We conducted a population-based study to evaluate trends in systemic treatment and survival of metastatic noncardia gastric cancer.
All patients ...with noncardia adenocarcinoma of the stomach, diagnosed between 1990 and 2011 in the Eindhoven Cancer Registry area in the Netherlands were included (N = 4797). We conducted multivariable logistic regression analysis to evaluate trends in administration of palliative chemotherapy and multivariable proportional hazards regression analyses to evaluate trends in crude overall survival.
The proportion of patients presenting with metastatic gastric cancer increased from 24% in 1990 to 44% in 2011 (P < 0.0001). The use of palliative chemotherapy increased, from 5% in 1990 to 36% in 2011, with a strong increase in particular after 2006 (P < 0.0001). Younger patients <50 years: adjusted odds ratio (ORadj) 3.9, P < 0.001; 50–59 years: ORadj 1.7, P = 0.01 and patients with a high socioeconomic status (ORadj 1.7, P = 0.01) more often received chemotherapy. In contrast, older patients (70–79 years: ORadj 0.3, P < 0.001; 80+ years: ORadj 0.02, P < 0.001), patients with comorbidity (ORadj 0.6, P = 0.03), linitis plastica (ORadj 0.5, P = 0.03) and multiple distant metastases (ORadj 0.5, P = 0.01) were less often treated with chemotherapy. A large hospital variation was observed in the administration of palliative chemotherapy (9%–27%). Median overall survival remained constant between 15 95% confidence interval (CI) 11.9–17.7 and 17 (95% CI 15.0–20.0) weeks (P = 0.10).
The increased administration of chemotherapy in patients with metastatic gastric cancer did not lead to an increase in population-based overall survival. Identification of the subgroup of patients which benefits from palliative chemotherapy is of utmost importance to avoid unnecessary treatment.
Background
Studies have shown minimally invasive esophagectomy (MIE) to be a feasible surgical technique in treating esophageal carcinoma. Postoperative complications have been extensively reviewed, ...but literature focusing on intraoperative complications is limited. The main objective of this study was to report major intraoperative complications and 90-day mortality during MIE for cancer.
Methods
Data were collected retrospectively from 10 European esophageal surgery centers. All intention-to-treat, minimally invasive laparoscopic/thoracoscopic esophagectomies with gastric conduit reconstruction for esophageal and GE junction cancers operated on between 2003 and 2019 were reviewed. Major intraoperative complications were defined as loss of conduit, erroneous transection of vascular structures, significant injury to other organs including bowel, heart, liver or lung, splenectomy, or other major complications including intubation injuries, arrhythmia, pulmonary embolism, and myocardial infarction.
Results
Amongst 2862 MIE cases we identified 98 patients with 101 intraoperative complications. Vascular injuries were the most prevalent, 41 during laparoscopy and 19 during thoracoscopy, with injuries to 18 different vessels. There were 24 splenic vascular or capsular injuries, 11 requiring splenectomies. Four losses of conduit due to gastroepiploic artery injury and six bowel injuries were reported. Eight tracheobronchial lesions needed repair, and 11 patients had significant lung parenchyma injuries. There were 2 on-table deaths. Ninety-day mortality was 9.2%.
Conclusions
This study offers an overview of the range of different intraoperative complications during minimally invasive esophagectomy. Mortality, especially from intrathoracic vascular injuries, appears significant.
Treatment for oesophageal cancer has evolved due to developments including the centralisation of surgery and introduction of neoadjuvant treatment. Therefore, this study evaluated trends in stage ...distribution, treatment and survival of oesophageal cancer patients in the last 26 years in the Netherlands.
Patients with oesophageal cancer diagnosed in the period 1989–2014 were selected from the Netherlands Cancer Registry. Patients were divided into two groups: non-metastatic (M0) and metastatic (M1). Trends in stage distribution, treatment and relative survival rates were evaluated according to histology.
Among all 35,760 patients, the percentage of an unknown tumour stage decreased from 34% to 10% during the study period, whereas the percentage of patients with metastatic disease increased from 21% to 34%. Among surgically treated patients 32% underwent a resection in a high-volume hospital in 2005 which increased to 92% in 2014. Use of neoadjuvant chemoradiotherapy increased in non-metastatic oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC) patients from respectively 4% and 2% in 2000–2004 to 43% and 26% in 2010–2014. Five-year relative survival increased from 8% to 22% for all patients; from 12% to 36% for non-metastatic OAC and from 9% to 27% for non-metastatic OSCC over 26 years. Median overall survival of metastatic patients improved from 18 to 22 weeks.
In the Netherlands, survival for oesophageal cancer patients improved significantly, especially in the period 2005–2014 which might be the result of better treatment related to the centralisation of surgery and introduction of neoadjuvant chemoradiotherapy.
•Five-year relative survival more than doubled in last 26 years for oesophageal cancer.•The use of neoadjuvant chemoradiotherapy increased significantly.•The percentage of patients who underwent surgery in a high-volume hospital increased.•Improved survival might be the result of the two abovementioned developments.
OBJECTIVE:To investigate the morbidity that is associated with the learning curve of minimally invasive esophagectomy.
BACKGROUND:Although learning curves have been described, it is currently unknown ...how much extra morbidity is associated with the learning curve of technically challenging surgical procedures.
METHODS:Prospectively collected data were retrospectively analyzed of all consecutive patients undergoing minimally invasive Ivor Lewis esophagectomy in 4 European expert centers. The primary outcome parameter was anastomotic leakage. Secondary outcome parameters were operative time and textbook outcome (“optimal outcome”). Learning curves were plotted using weighted moving average and CUSUM analysis was used to determine after how many cases the plateau was reached. Learning associated morbidity was calculated with area under the curve analysis.
RESULTS:This study included 646 patients. Three of the 4 hospitals reached the plateau of 8% anastomotic leakage. The length of the learning curve was 119 cases. The mean incidence of anastomotic leakage decreased from 18.8% during the learning phase to 4.5% after the plateau had been reached (P < 0.001). Thirty-six extra patients (10.1% of all patients operated on during the learning curve) experienced learning associated anastomotic leakage, that could have been avoided if patients were operated by surgeons who had completed the learning curve. The incidence of textbook outcome increased from 28% to 53% and the mean operative time decreased from 344 minutes to 270 minutes.
CONCLUSIONS:A considerable number of 36 extra patients (10.1%) experienced learning associated anastomotic leakage. More research is urgently needed to investigate how learning associated morbidity can be reduced to increase patient safety during learning curves.
Urine poses an attractive non-invasive means for obtaining liquid biopsies for oncological diagnostics. Especially molecular analysis on urinary DNA is a rapid growing field. However, optimal and ...practical storage conditions that result in preservation of urinary DNA, and in particular hypermethylated DNA (hmDNA), are yet to be determined.
To determine the most optimal and practical conditions for urine storage that result in adequate preservation of DNA for hmDNA analysis.
DNA yield for use in methylation analysis was determined by quantitative methylation specific PCR (qMSP) targeting the ACTB and RASSF1A genes on bisulfite modified DNA. First, DNA yield (ACTB qMSP) was determined in a pilot study on urine samples of healthy volunteers using two preservatives (Ethylenediaminetetraacetic acid (EDTA) and Urine Conditioning Buffer, Zymo Research) at four different temperatures (room temperature (RT), 4°C, -20°C, -80°C) for four time periods (1, 2, 7, 28 days). Next, hmDNA levels (RASSF1A qMSP) in stored urine samples of patients suffering from bladder cancer (n = 10) or non-small cell lung cancer (NSCLC; n = 10) were measured at day 0 and 7 upon storage with and without the addition of 40mM EDTA and/or 20 μl/ml Penicillin Streptomycin (PenStrep) at RT and 4°C.
In the pilot study, DNA for methylation analysis was only maintained at RT upon addition of preserving agents. In urine stored at 4°C for a period of 7 days or more, the addition of either preserving agent yielded a slightly better preservation of DNA. When urine was stored at -20 °C or -80 °C for up to 28 days, DNA was retained irrespective of the addition of preserving agents. In bladder cancer and NSCLC samples stored at RT loss of DNA was significantly less if EDTA was added compared to no preserving agents (p<0.001). Addition of PenStrep did not affect DNA preservation (p>0.99). Upon storage at 4°C, no difference in DNA preservation was found after the addition of preserving agents (p = 0.18). The preservation of methylated DNA (RASSF1A) was strongly correlated to that of unmethylated DNA (ACTB) in most cases, except when PCR values became inaccurate.
Addition of EDTA offers an inexpensive preserving agent for urine storage at RT up to seven days allowing for reliable hmDNA analysis. To avoid bacterial overgrowth PenStrep can be added without negatively affecting DNA preservation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Centralization of surgery has been shown to improve outcomes for oesophageal and pancreatic cancer, and has been implemented for gastric cancer since 2012 in the Netherlands. This study ...evaluated the impact of centralizing gastric cancer surgery on outcomes for all patients with gastric cancer.
Methods
Patients diagnosed with non‐cardia gastric adenocarcinoma in the intervals 2009–2011 and 2013–2015 were selected from the Netherlands Cancer Registry. Clinicopathological data, treatment characteristics and mortality were assessed for the periods before (2009–2011) and after (2013–2015) centralization. Cox regression analyses were used to assess differences in overall survival between these intervals.
Results
A total of 7204 patients were included. Resection rates increased slightly from 37·6 per cent before to 39·6 per cent after centralization (P = 0·023). Before centralization, 50·1 per cent of surgically treated patients underwent gastrectomy in hospitals that performed fewer than ten procedures annually, compared with 9·2 per cent after centralization. Patients who had gastrectomy in the second interval were younger and more often underwent total gastrectomy (29·3 per cent before versus 41·2 per cent after centralization). Thirty‐day postoperative mortality rates dropped from 6·5 to 4·1 per cent (P = 0·004), and 90‐day mortality rates decreased from 10·6 to 7·2 per cent (P = 0·002). Two‐year overall survival rates increased from 55·4 to 58·5 per cent among patients who had gastrectomy (P = 0·031) and from 27·1 to 29·6 per cent for all patients (P = 0·003). Improvements remained after adjustment for case mix; however, adjustment for hospital volume attenuated this association for surgically treated patients.
Conclusion
Centralization of gastric cancer surgery was associated with reduced postoperative mortality and improved survival.
Practice makes perfect?
Weekly chemotherapy and concurrent radiotherapy for 5 weeks before curative resection in patients with esophageal or esophagogastric-junction cancer resulted in a pathologically complete response in ...29% of patients and doubled the median overall survival to 4 years.
With new diagnoses in more than 480,000 patients annually, esophageal cancer is the eighth most common cancer worldwide.
1
It is a highly lethal disease, causing more than 400,000 deaths per year.
2
The incidence of esophageal adenocarcinoma is rapidly rising, whereas that of squamous-cell carcinoma remains unchanged.
3
Despite adequate preoperative staging, 25% of patients treated with primary surgery have microscopically positive resection margins (R1), and the 5-year survival rate rarely exceeds 40%.
4
The role of neoadjuvant chemoradiotherapy has been debated for several decades. In most randomized trials, no survival benefit could be shown, and the trials were criticized for inadequate trial . . .
Background
In most western European countries perioperative chemotherapy is a part of standard curative treatment for gastric cancer. Nevertheless, recurrence rates remain high after multimodality ...treatment. This study examines patterns of recurrence in patients receiving perioperative chemotherapy with surgery for gastric cancer in a real-world setting.
Methods
All patients diagnosed with gastric adenocarcinoma between 2010 and 2015 who underwent at least preoperative chemotherapy and a gastrectomy with curative intent (cT1N+/cT2-4a,X; any cN; cM0) in 18 Dutch hospitals were selected from the Netherlands Cancer Registry. Additional data on chemotherapy and recurrence were collected from medical records. Rates, patterns, and timing of recurrence were examined. Multivariable Cox proportional hazard analyses were used to determine prognostic factors for recurrence.
Results
408 patients were identified. After a median follow-up of 27.8 months, 36.8% of the gastric cancer patients had a recurrence of which the majority (88.8%) had distant metastasis. The 1-year recurrence-free survival was 71.8%. The risk of recurrence was higher in patients with an ypN+ stage (HR 4.92, 95% CI 3.35–7.24), partial or no tumor regression (HR 2.63, 95% CI 1.22–5.64), 3 instead of ≥ 6 chemotherapy cycles (HR 3.04, 95% CI 1.99–4.63), R1 resection (HR 1.52, 95% CI 1.02–2.26), and < 15 resected lymph nodes (HR 1.64, 95% CI 1.14–2.37).
Conclusion
A considerable amount of gastric cancer patients who were treated with curative intent developed a recurrence despite surgery and perioperative treatment. The majority developed distant metastases, therefore, multimodality treatment approaches should be focused on the prevention of distant rather than locoregional recurrences to improve survival.
Abstract Aim To evaluate trends in the risk of local recurrences after breast-conserving treatment (BCT) and to examine the impact of local recurrence (LR) on distant relapse-free survival in a ...large, population-based cohort of women aged ⩽40 years with early-stage breast cancer. Methods All women ( n = 1143) aged ⩽40 years with early-stage (pT1-2/cT1-2, N0-2, M0) breast cancer who underwent BCT in the south of the Netherlands between 1988 and 2010 were included. BCT consisted of local excision of the tumour followed by irradiation of the breast. Results After a median follow-up of 8.5 (0.1–24.6) years, 176 patients had developed an isolated LR. The 5-year LR-rate for the subgroups treated in the periods 1988–1998, 1999–2005 and 2006–2010 were 9.8% (95% confidence interval (CI) 7.1–12.5), 5.9% (95% CI 3.2–8.6) and 3.3% (95% CI 0.6–6.0), respectively ( p = 0.006). In a multivariate analysis, adjuvant systemic treatment was associated with a reduced risk of LR of almost 60% (hazard ratio (HR) 0.42; 95% CI 0.28–0.60; p < 0.0001). Patients who experienced an early isolated LR (⩽5 years after BCT) had a worse distant relapse-free survival compared to patients without an early LR (HR 1.83; 95% CI 1.27–2.64; p = 0.001). Late local recurrences did not negatively affect distant relapse-free survival (HR 1.24; 95% CI 0.74–2.08; p = 0.407). Conclusion Local control after BCT improved significantly over time and appeared to be closely related to the increased use and effectiveness of systemic therapy. These recent results underline the safety of BCT for young women with early-stage breast cancer.
Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard of care for patients with esophageal or junctional cancer, but the long-term impact of nCRT on health-related quality of life (HRQOL) ...is unknown. The purpose of this study is to compare very long-term HRQOL in long-term survivors of esophageal cancer who received nCRT plus surgery or surgery alone.
Patients were randomly assigned to receive nCRT (carboplatin/paclitaxel with 41.4-Gy radiotherapy) plus surgery or surgery alone. HRQOL was measured using EORTC-QLQ-C30, EORTC-QLQ-OES24 and K-BILD questionnaires after a minimum follow-up of 6 years. To allow for examination over time, EORTC-QLQ-C30 and QLQ-OES24 questionnaire scores were compared with pretreatment and 12 months postoperative questionnaire scores. Physical functioning (QLQ-C30), eating problems (QLQ-OES24) and respiratory problems (K-BILD) were predefined primary end points. Predefined secondary end points were global quality of life and fatigue (both QLQ-C30).
After a median follow-up of 105 months, 123/368 included patients (33%) were still alive (70 nCRT plus surgery, 53 surgery alone). No statistically significant or clinically relevant differential effects in HRQOL end points were found between both groups. Compared with 1-year postoperative levels, eating problems, physical functioning, global quality of life and fatigue remained at the same level in both groups. Compared with pretreatment levels, eating problems had improved (Cohen’s d −0.37, P = 0.011) during long-term follow-up, whereas physical functioning and fatigue were not restored to pretreatment levels in both groups (Cohen’s d −0.56 and 0.51, respectively, both P < 0.001).
Although physical functioning and fatigue remain reduced after long-term follow-up, no adverse impact of nCRT is apparent on long-term HRQOL compared with patients who were treated with surgery alone. In addition to the earlier reported improvement in survival and the absence of impact on short-term HRQOL, these results support the view that nCRT according to CROSS can be considered as a standard of care.
Netherlands Trial Register NTR487.
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