Medical treatment options and strategies for Crohn's disease (CD) have changed over the past decades. To assess its impact, we studied the evolution of the long-term disease outcome in the Dutch ...Inflammatory Bowel Disease South Limburg (IBDSL) cohort.
In total, 1,162 CD patients were included. Three eras were distinguished: 1991-1998 (n=316), 1999-2005 (n=387), and 2006-2011 (n=459), and patients were followed until 2014. Medication exposure and the rates of hospitalization, surgery, and phenotype progression were estimated using Kaplan-Meier survival analyses and compared between eras by multivariable Cox regression models. Second, propensity score matching was used to assess the relation between medication use and the long-term outcome.
Over time, the immunomodulator exposure rate increased from 30.6% in the era 1991-1998 to 70.8% in the era 2006-2011 at 5 years. Similar, biological exposure increased from 3.1% (era 1991-1998) to 41.2% (era 2006-2011). In parallel, the hospitalization rate attenuated from 65.9% to 44.2% and the surgery rate from 42.9% to 17.4% at 5 years, respectively (both P<0.01). Progression to a complicated phenotype has not changed over time (21.2% in the era 1991-1998 vs. 21.3% in the era 2006-2011, P=0.93). Immunomodulator users had a similar risk of hospitalization, surgery, or phenotype progression as propensity score-matched nonusers (P>0.05 for all analyses). Similar results were found for biological users (P>0.05 for all analyses).
Between 1991 and 2014, the hospitalization and surgery rates decreased, whereas progression to complicated disease is still common in CD. These improvements were not significantly related to the use of immunomodulators and biologicals.
Elderly onset (EO) inflammatory bowel disease (IBD) may become a more common entity as a result of population aging and the rising IBD incidence. Its management is challenging, because of ...multimorbidity, polypharmacy, and frailty. Insight into the long-term outcome is essential for optimal patient counseling and treatment. We studied the incidence and disease outcome of elderly-onset IBD in direct comparison to adult-onset (AO) IBD.
All 2823 cases with IBD from the Dutch population-based IBD South Limburg cohort, diagnosed between 1991 and 2011, were included. Long-term outcome (hospitalization, surgery, and disease phenotype) was compared between AO (<60 years at diagnosis) and EO (≥60 years at diagnosis) disease, for Crohn's disease (CD) and ulcerative colitis (UC) separately.
In total, 1162 patients with CD (136 EO/1026 AO) and 1661 patients with UC (373 EO/1288 AO) were included. The EO IBD incidence increased from 11.71 per 100,000 persons in 1991 to 23.66 per 100,000 persons in 2010, P < 0.01. Immunomodulators were less often used in EO CD (61.8% versus 77.1%, P = 0.03) and EO UC (22.8% versus 35.4%, P < 0.01), even as biologicals (25.1% versus 55.1%, P = 0.03 and 7.8% versus 18.0%, P < 0.01, respectively). No differences were observed in surgery risk (CD: hazard ratio HR 1.19; 95% confidence interval CI, 0.85-1.67 and UC: HR, 0.88; 95% CI, 0.53-1.46), or in CD phenotype progression (HR, 0.81; 95% CI, 0.52-1.25), but more patients with EO UC required hospitalization (HR, 1.29; 95% CI, 1.01-1.63).
EO IBD is rising, warranting physicians' alertness for IBD in elderly patients. The long-term outcome was not different from AO disease, despite a less frequent use of immunomodulators and biologicals.
After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response ...of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations.
The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin area under the curve 2 mg/mL per min plus paclitaxel 50 mg/m2 of body-surface area combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4–6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET–CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12–14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed.
Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% 95% CI 17–50) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% 95% CI 4–23) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% 95% CI 17–44). PET–CT missed six of 41 TRG3 or TRG4 tumours (15% 95% CI 7–28). PET–CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas).
After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET–CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803).
Dutch Cancer Society.
The management of inflammatory bowel disease (IBD) has changed since the mid‐1990s (e.g., use of thiopurines/anti‐TNFα agents, improved surveillance programs), possibly affecting cancer risk. To ...establish current cancer risk in IBD, updates are warranted from cohorts covering this time span, and detailed enough to study associations with phenotype and medication. We studied intestinal‐, extra‐intestinal‐ and overall cancer risk in the Dutch population‐based IBDSL cohort. In total, 1,157 Crohn's disease (CD) and 1,644 ulcerative colitis (UC) patients were diagnosed between 1991 and 2011, and followed until 2013. Standardized incidence ratios (SIRs) were calculated for CD and UC separately, as well as for gender‐, phenotype‐, disease duration‐, diagnosis era‐ and medication groups. We found an increased risk for colorectal cancer in CD patients with colon involvement (SIR 2.97; 95% CI 1.08–6.46), but not in the total CD or UC population. In addition, CD patients were at increased risk for hematologic‐ (2.41; 1.04–4.76), overall skin‐ (1.55; 1.06–2.19), skin squamous cell‐ (SCC; 3.83; 1.83–7.04) and overall cancer (1.28; 1.01–1.60), whereas UC patients had no increased risk for extra‐intestinal‐ and overall cancer. Finally, in a medication analysis on CD and UC together, long‐term immunosuppression exposure (>12 months) was associated with an increased risk for hematologic cancer, non‐Hodgkin lymphoma, SCC and overall cancer, and this increase was mainly attributed to thiopurines. IBD patients with long‐term immunosuppression exposure can be considered as having a higher cancer risk, and our data support the advice in recent IBD guidelines to consider skin cancer screening in these patients.
What's new?
The management of inflammatory bowel disease (IBD) has changed markedly since the mid‐1990s, possibly affecting cancer risk. To establish current cancer risk, updates are warranted from cohorts covering this timespan and detailed enough to study associations with phenotype and medication. Here, using the Dutch population‐based IBDSL cohort, the authors found that colorectal cancer risk is currently lower in both CD and UC than previously mentioned in literature. CD patients however show an increased overall cancer risk. Altogether, long‐term immunosuppression exposure brings an additional cancer risk to IBD patients, a finding that may be relevant in other auto‐immune diseases with similar medication.
To investigate the reproducibility of diffusion-weighted magnetic resonance imaging (DW-MRI) in assessing tumor response early in the course of neoadjuvant chemoradiotherapy in patients with operable ...esophageal cancer.
Eleven male patients (mean age 54.8 years) with newly diagnosed esophageal cancer underwent DW-MRI before and 10 days after start of chemoradiotherapy. Reproducibility of apparent diffusion coefficient (ADC) measurements by manual (freehand) and semi-automated volumetric methods was assessed.
Interobserver reproducibility for the assessment of mean tumor ADC by the manual measurement method was good, with an ICC of 0.69 (95% CI, 0.36 to 0.85; P = 0.001). Interobserver reproducibility for the assessment of mean tumor ADC by the semi-automated volumetric measurement method was very good, with an ICC of 0.96 (95% CI, 0.91 to 0.98; P<0.001).
Semi-automated volumetric ADC measurements have higher reproducibility than manual ADC measurements in assessing tumor response to chemoradiotherapy in patients with esophageal adenocarcinoma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE:This study compared outcomes of patients with esophageal cancer and clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) undergoing active surveillance or immediate ...surgery.
BACKGROUND:Since nearly one-third of patients with esophageal cancer show pathologically complete response after nCRT according to CROSS regimen, the oncological benefit of immediate surgery in cCR is topic of debate.
METHODS:Patients with cCR based on endoscopic biopsies and endoscopic ultrasonography with fine-needle aspiration initially declining or accepting immediate surgery after nCRT were identified between 2011 and 2018. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), rate and timing of distant dissemination, and postoperative outcomes.
RESULTS:Some 98 patients with cCR were identified31 in the active surveillance- and 67 in the immediate surgery group with median follow-up of survivors of 27.7 and 34.8 months, respectively. Propensity score matching resulted in 2 comparable groups (n = 29 in both groups). Patients undergoing active surveillance or immediate surgery had a 3-year OS of 77% and 55% (HR 0.41; 95% CI 0.14–1.20, P = 0.104), respectively. The 3-year PFS was 60% and 54% (HR 1.08; 95% CI 0.44–2.67, P = 0.871), respectively. Patients undergoing active surveillance or immediate surgery had a comparable distant dissemination rate (both groups 28%), radical resection rate (both groups 100%), and severity of postoperative complications (Clavien–Dindo grade≥343% vs 45%, respectively).
CONCLUSION:In this retrospective study, OS and PFS in patients with cCR undergoing active surveillance or immediate surgery were not significantly different. Active surveillance with postponed surgery for recurrent disease was not associated with a higher distant dissemination rate or more severe adverse postoperative outcomes.
The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these ...outcomes.
We performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies.
We included 1000 children born to 626 mothers (381 (61%) Crohn's disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population.
In our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies.
Endoscopic ultrasound (EUS) measurements of residual thickness and residual area have been suggested to correlate with histopathological residual tumor after neoadjuvant chemoradiotherapy (nCRT) for ...esophageal cancer. This study assessed the predictive value of EUS-based measurements using tumor thickness and tumor area before nCRT, and residual thickness and residual area 6 and 12 weeks after completion of nCRT for detection of residual disease.
This was a substudy of the diagnostic multicenter preSANO trial. The primary end point of the current study was the percentage of tumor regression grade (TRG) 3 - 4 (> 10 % vital tumor cells) residual disease that was detected using EUS-based measurements. Associations of absolute measurements of residual thickness/area and proportional change compared with baseline were evaluated. In the case of a statistically significant association, optimal cut-offs to distinguish TRG3 - 4 residual disease from TRG1 (no vital tumor cells) were determined using Youden's J index.
138 patients were included. Residual thickness and residual area were statistically significantly associated with TRG3 - 4 residual disease 12 weeks after completion of nCRT (odds ratio 1.36,
< 0.01 and 1.64,
= 0.02, respectively). The cut-off for residual thickness was 4.5 mm, which correctly detected 87 % of TRG3 - 4 residual disease and 52 % of TRG1. The cut-off for residual area was 0.92 cm
, which detected 89 % of TRG3 - 4 residual disease and 40 % of TRG1.
EUS measurements of residual thickness and residual area adequately detected TRG3 - 4 residual disease with a sensitivity of almost 90 % 12 weeks after completion of nCRT. Hence, residual thickness and residual area may aid in the restaging of esophageal cancer after nCRT.
Abstract
Background
Active surveillance is being investigated as an alternative to standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer. It is unknown whether dysphagia ...persists or develops when the oesophagus is preserved after neoadjuvant chemoradiotherapy. The aim of this study was to assess the prevalence and severity of dysphagia during active surveillance in patients with an ongoing response.
Methods
Patients who underwent active surveillance were identified from the Surgery As Needed for Oesophageal cancer (‘SANO’) trial. Patients without evidence of residual oesophageal cancer until at least 6 months after neoadjuvant chemoradiotherapy were included. Study endpoints were assessed at time points that patients were cancer-free and remained cancer-free for the next 4 months. Dysphagia scores were evaluated at 6, 9, 12, and 16 months after neoadjuvant chemoradiotherapy. Scores were based on the European Organisation for Research and Treatment of Cancer oesophago-gastric quality-of-life questionnaire 25 (EORTC QLQ-OG25) (range 0–100; no to severe dysphagia). The rate of patients with a (non-)traversable stenosis was determined based on all available endoscopy reports.
Results
In total, 131 patients were included, of whom 93 (71.0 per cent) had adenocarcinoma, 93 (71.0 per cent) had a cT3–4a tumour, and 33 (25.2 per cent) had a tumour circumference of greater than 75 per cent at endoscopy; 60.8 to 71.0 per cent of patients completed questionnaires per time point after neoadjuvant chemoradiotherapy. At all time points after neoadjuvant chemoradiotherapy, median dysphagia scores were 0 (interquartile range 0–0). Two patients (1.5 per cent) underwent an intervention for a stenosis: one underwent successful endoscopic dilatation; and the other patient required temporary tube feeding. Notably, these patients did not participate in questionnaires.
Conclusion
Dysphagia and clinically relevant stenosis are uncommon during active surveillance.
Dysphagia appears uncommon in patients with a clinically complete response until 16 months after neoadjuvant chemoradiotherapy according to the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (‘CROSS’) regimen. In patients who might choose between standard surgery and active surveillance, the occurrence of persisting dysphagia during active surveillance is not an issue that needs to be taken into account.
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