Background
This prospective multicentre study was performed to quantify the number of patients with minimal residual disease (ypT0–1) after neoadjuvant chemoradiotherapy and transanal endoscopic ...microsurgery (TEM) for rectal cancer.
Methods
Patients with clinically staged T1–3 N0 distal rectal cancer were treated with long‐course chemoradiotherapy. Clinical response was evaluated 6–8 weeks later and TEM performed. Total mesorectal excision was advocated in patients with residual disease (ypT2 or more).
Results
The clinical stage was cT1 N0 in ten patients, cT2 N0 in 29 and cT3 N0 in 16 patients. Chemoradiotherapy‐related complications of at least grade 3 occurred in 23 of 55 patients, with two deaths from toxicity, and two patients did not have TEM or major surgery. Among 47 patients who had TEM, ypT0–1 disease was found in 30, ypT0 N1 in one, ypT2 in 15 and ypT3 in one. Local recurrence developed in three of the nine patients with ypT2 tumours who declined further surgery. Postoperative complications grade I–IIIb occurred in 13 of 47 patients after TEM and in five of 12 after (completion) surgery. After a median follow‐up of 17 months, four local recurrences had developed overall, three in patients with ypT2 and one with ypT1 disease.
Conclusion
TEM after chemoradiotherapy enabled organ preservation in one‐half of the patients with rectal cancer.
Organ preservation feasible
Background
Transanal total mesorectal excision
(
TaTME) is a new complex technique with potential to improve the quality of surgical mesorectal excision for patients with mid and low rectal cancer. ...The procedure is technically challenging and has shown to be associated with a relative long learning curve which might hamper widespread adoption. Therefore, a national structured training pathway for TaTME has been set up in the Netherlands to allow safe implementation. The aim of this study was to monitor safety and efficacy of the training program with 12 centers.
Methods
Short-term outcomes of the first ten TaTME procedures were evaluated in 12 participating centers in the Netherlands within the national structured training pathway. Consecutive patients operated during and after the proctoring program for rectal carcinoma with curative intent were included. Primary outcome was the incidence of intraoperative complications, secondary outcomes included postoperative complications and pathological outcomes.
Results
In October 2018, 12 hospitals completed the training program and from each center the first 10 patients were included for evaluation. Intraoperative complications occurred in 4.9% of the cases. The clinicopathological outcome reported 100% for complete or nearly complete specimen, 100% negative distal resection margin, and the circumferential resection margin was positive in 5.0% of patients. Overall postoperative complication rate was 45.0%, with 19.2% Clavien–Dindo ≥ III and an anastomotic leak rate of 17.3%.
Conclusions
This study shows that the nationwide structured training program for TaTME delivers safe implementation of TaTME in terms of intraoperative and pathology outcomes within the first ten consecutive cases in each center. However, postoperative morbidity is substantial even within a structured training pathway and surgeons should be aware of the learning curve of this new technique.
Background
The risks of local recurrence and treatment‐related morbidity need to be balanced after local excision of early rectal cancer. The aim of this meta‐analysis was to determine oncological ...outcomes after local excision of pT1–2 rectal cancer followed by no additional treatment (NAT), completion total mesorectal excision (cTME) or adjuvant (chemo)radiotherapy (aCRT).
Methods
A systematic search was conducted in PubMed, Embase and the Cochrane Library. The primary outcome was local recurrence. Statistical analysis included calculation of the weighted average of proportions.
Results
Some 73 studies comprising 4674 patients were included in the analysis. Sixty‐two evaluated NAT, 13 cTME and 28 aCRT. The local recurrence rate for NAT among low‐risk pT1 tumours was 6·7 (95 per cent c.i. 4·8 to 9·3) per cent. There were no local recurrences of low‐risk pT1 tumours after cTME or aCRT. The local recurrence rate for high‐risk pT1 tumours was 13·6 (8·0 to 22·0) per cent for local excision only, 4·1 (1·7 to 9·4) per cent for cTME and 3·9 (2·0 to 7·5) per cent for aCRT. Local recurrence rates for pT2 tumours were 28·9 (22·3 to 36·4) per cent with NAT, 4 (1 to 13) per cent after cTME and 14·7 (11·2 to 19·0) per cent after aCRT.
Conclusion
There is a substantial risk of local recurrence in patients who receive no additional treatment after local excision, especially those with high‐risk pT1 and pT2 rectal cancer. The lowest recurrence risk is provided by cTME; aCRT has outcomes comparable to those of cTME for high‐risk pT1 tumours, but shows a higher risk for pT2 tumours.
Antecedentes
Tras una resección temprana de un cáncer de recto localizado, hay que considerar el equilibrio entre el riesgo de recidiva local y la morbilidad relacionada con el tratamiento. El objetivo de este metaanálisis era determinar los resultados oncológicos tras la resección de un cáncer de recto pT1‐T2 seguida de ningún tratamiento adicional (no additional treatment, NAT), escisión total del mesorrecto (completion total mesorectal excision, cTME) o quimiorradioterapia adyuvante (adjuvant chemoradiotherapy, aCRT).
Methods
Se llevó a cabo una búsqueda sistemática en PubMed, Embase y biblioteca Cochrane. La variable principal de resultado era la recidiva local (local recurrence, LR). En el análisis estadístico se calcularon las medias ponderadas de proporciones.
Resultados
Se incluyeron en el análisis 76 estudios con un total de 4.793 pacientes. NAT fue evaluada en 72 estudios, cTME en 13 y aCRT en 28. La tasa de LR para NAT en tumores pT1 de bajo riesgo era de 6,7% (i.c. del 95% 4,8‐9,3). No se observaron casos de LR en tumores pT1 de bajo riesgo tras cTME o aCRT. La tasa de LR para tumores pT1 de alto riesgo fue de 13,6% (i.c. del 95% 8,0‐22,0) para la resección local como único tratamiento, 4,1% (i.c. del 95% 1,7‐9,4) para cTME y 3,9% (i.c. del 95% 2,0‐7,5) para aCRT. La tasa de LR para tumores pT2 fue de 28,9% (i.c. del 95% 22,3‐36,4) para NAT, 4,3% (i.c. del 95% 1,4‐12,5) para cTME y 14,7% (i.c. del 95% 11,2‐19,0) para aCRT.
Conclusión
Tras la resección local de cáncer pT1 de alto riesgo y pT2, existe un riesgo sustancial de recidiva local en ausencia de tratamiento adicional. La escisión total del mesorrecto se asocia con el menor riesgo de recidiva. La quimiorradioterapia adyuvante ofrece resultados similares a la escisión total del mesorrecto en tumores pT1 de alto riesgo, pero presenta un mayor riesgo en tumores pT2.
This meta‐analysis showed that patients who undergo no additional treatment after local excision of pT1–2 rectal cancer have a high risk of local recurrence, especially those with high‐risk pT1 and pT2 lesions. The risk of local recurrence after adjuvant (chemo)radiotherapy for high‐risk pT1 tumours seems to be similar to that after completion TME. For pT2 tumours, adjuvant (chemo)radiotherapy seems less effective than radical surgery.
No additional therapy after local excision of pT1‐2 associated with high risk of local recurrence
To examine barriers to initiation and continuation of mental health treatment among individuals with common mental disorders.
Data were from the World Health Organization (WHO) World Mental Health ...(WMH) surveys. Representative household samples were interviewed face to face in 24 countries. Reasons to initiate and continue treatment were examined in a subsample (n = 63,678) and analyzed at different levels of clinical severity.
Among those with a DSM-IV disorder in the past 12 months, low perceived need was the most common reason for not initiating treatment and more common among moderate and mild than severe cases. Women and younger people with disorders were more likely to recognize a need for treatment. A desire to handle the problem on one's own was the most common barrier among respondents with a disorder who perceived a need for treatment (63.8%). Attitudinal barriers were much more important than structural barriers to both initiating and continuing treatment. However, attitudinal barriers dominated for mild-moderate cases and structural barriers for severe cases. Perceived ineffectiveness of treatment was the most commonly reported reason for treatment drop-out (39.3%), followed by negative experiences with treatment providers (26.9% of respondents with severe disorders).
Low perceived need and attitudinal barriers are the major barriers to seeking and staying in treatment among individuals with common mental disorders worldwide. Apart from targeting structural barriers, mainly in countries with poor resources, increasing population mental health literacy is an important endeavor worldwide.
Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among ...employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression.
We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol.
We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13 and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32).
Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.
Summary Background Case series suggest that laparoscopic peritoneal lavage might be a promising alternative to sigmoidectomy in patients with perforated diverticulitis. We aimed to assess the ...superiority of laparoscopic lavage compared with sigmoidectomy in patients with purulent perforated diverticulitis, with respect to overall long-term morbidity and mortality. Methods We did a multicentre, parallel-group, randomised, open-label trial in 34 teaching hospitals and eight academic hospitals in Belgium, Italy, and the Netherlands (the Ladies trial). The Ladies trial is split into two groups: the LOLA group comparing laparoscopic lavage with sigmoidectomy and the DIVA group comparing Hartmann's procedure with sigmoidectomy plus primary anastomosis. The DIVA section of this trial is still underway but here we report the results of the LOLA section. Patients with purulent perforated diverticulitis were enrolled for LOLA, excluding patients with faecal peritonitis, aged older than 85 years, with high-dose steroid use (≥20 mg daily), and haemodynamic instability. Patients were randomly assigned (2:1:1; stratified by age <60 years vs ≥60 years) using secure online computer randomisation to laparoscopic lavage, Hartmann's procedure, or primary anastomosis in a parallel design after diagnostic laparoscopy. Patients were analysed according to a modified intention-to-treat principle and were followed up after the index operation at least once in the outpatient setting and after sigmoidoscopy and stoma reversal, according to local protocols. The primary endpoint was a composite endpoint of major morbidity and mortality within 12 months. This trial is registered with ClinicalTrials.gov , number NCT01317485. Findings Between July 1, 2010, and Feb 22, 2013, 90 patients were randomly assigned in the LOLA section of the Ladies trial when the study was terminated by the data and safety monitoring board because of an increased event rate in the lavage group. Two patients were excluded for protocol violations. The primary endpoint occurred in 30 (67%) of 45 patients in the lavage group and 25 (60%) of 42 patients in the sigmoidectomy group (odds ratio 1·28, 95% CI 0·54–3·03, p=0·58). By 12 months, four patients had died after lavage and six patients had died after sigmoidectomy (p=0·43). Interpretation Laparoscopic lavage is not superior to sigmoidectomy for the treatment of purulent perforated diverticulitis. Funding Netherlands Organisation for Health Research and Development.
Purpose The 70-gene prognosis signature (van't Veer et al., Nature 415(6871):530-536, 2002) may improve the selection of lymph node-negative breast cancer patients for adjuvant systemic therapy. ...Optimal validation of prognostic classifiers is of great importance and we therefore wished to evaluate the prognostic value of the 70-gene prognosis signature in a series of relatively recently diagnosed lymph node negative breast cancer patients. Methods We evaluated the 70-gene prognosis signature in an independent representative series of patients with invasive breast cancer (N = 123; <55 years; pT1-2N0; diagnosed between 1996 and 1999; median follow-up 5.8 years) by classifying these patients as having a good or poor prognosis signature. In addition, we updated the follow-up of the node-negative patients of the previously published validation-series (Van de Vijver et al., N Engl J Med 347(25):1999-2009, 2002; N = 151; median follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature was compared with that of four commonly used clinicopathological risk indexes. The endpoints were distant metastasis (as first event) free percentage (DMFP) and overall survival (OS). Results The 5-year OS was 82 ± 5% in poor (48%) and 97 ± 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2-9.6; P = 0.021). The 5-years DMFP was 78 ± 6% in poor and 98 ± 2% in good prognosis signature patients (HR 5.7; 95% CI 1.6-20; P = 0.007). In the updated series (N = 151; 60% poor vs. 40% good), the 10-year OS was 51 ± 5% and 94 ± 3% (HR 10.7; 95% CI 3.9-30; P < 0.01), respectively. The DMFP was 50 ± 6% in poor and 86 ± 5% in good prognosis signature patients (HR 5.5; 95% CI 2.5-12; P < 0.01). In multivariate analysis, the prognosis signature was a strong independent prognostic factor in both series, outperforming the clinicopathological risk indexes. Conclusion The 70-gene prognosis signature is also an independent prognostic factor in node-negative breast cancer patients for women diagnosed in recent years.
Background
Treatment strategies for diverticulitis with abscess formation have shifted from (emergency) surgical treatment to non‐surgical management (antibiotics with or without percutaneous ...drainage (PCD)). The aim was to assess outcomes of non‐surgical treatment and to identify risk factors for adverse outcomes.
Methods
Patients with a first episode of CT‐diagnosed diverticular abscess (modified Hinchey Ib or II) between January 2008 and January 2015 were included retrospectively, if initially treated non‐surgically. Baseline characteristics, short‐term (within 30 days) and long‐term treatment outcomes were recorded. Treatment failure was a composite outcome of complications (perforation, colonic obstruction and fistula formation), readmissions, persistent diverticulitis, emergency surgery, death, or need for PCD in the no‐PCD group. Regression analyses were used to analyse risk factors for treatment failure, recurrences and surgery.
Results
Overall, 447 patients from ten hospitals were included (Hinchey Ib 215; Hinchey II 232), with a median follow‐up of 72 (i.q.r. 55–93) months. Most patients were treated without PCD (332 of 447, 74·3 per cent). Univariable analyses, stratified by Hinchey grade, showed no differences between no PCD and PCD in short‐term treatment failure (Hinchey I: 22·3 versus 33 per cent, P = 0·359; Hinchey II: 25·9 versus 36 per cent, P = 0·149) or emergency surgery (Hinchey I: 5·1 versus 6 per cent, P = 0·693; Hinchey II: 10·4 versus 15 per cent, P = 0·117), but significantly more complications were found in patients with Hinchey II disease undergoing PCD (12 versus 3·7 per cent; P = 0·032). Multivariable analyses showed that treatment strategy (PCD versus no PCD) was not independently associated with short‐term treatment failure (odds ratio (OR) 1·47, 95 per cent c.i. 0·81 to 2·68), emergency surgery (OR 1·29, 0·56 to 2·99) or long‐term surgery (hazard ratio 1·08, 95 per cent c.i. 0·69 to 1·69). Abscesses of at least 3 cm in diameter were associated with short‐term treatment failure (OR 2·05, 1·09 to 3·86), and abscesses of 5 cm or larger with the need for surgery during short‐term follow‐up (OR 2·96, 1·03 to 8·13).
Conclusion
The choice between PCD with antibiotics or antibiotics alone as initial non‐surgical treatment of Hinchey Ib and II diverticulitis does not seem to influence outcomes.
This multicentre retrospective cohort study included 447 patients with Hinchey Ib and II diverticular abscesses, who were treated with antibiotics, with or without percutaneous drainage. Abscesses of 3 and 5 cm in size were at higher risk of short‐term treatment failure and emergency surgery respectively. Initial non‐surgical treatment of Hinchey Ib and II diverticular abscesses was comparable between patients treated with antibiotics only and those who underwent percutaneous drainage in combination with antibiotics, with regard to short‐ and long‐term outcomes.
Most do not need drainage
Aims Multidetector computed tomography coronary angiography (CTA) has emerged as a feasible imaging modality for non-invasive assessment of coronary artery disease (CAD). Recently, 320-row CTA ...systems were introduced, with 16 cm anatomical coverage, allowing image acquisition of the entire heart within a single heart beat. The aim of the present study was to assess the diagnostic accuracy of 320-row CTA in patients with known or suspected CAD. Methods and results A total of 64 patients (34 male, mean age 61 ± 16 years) underwent CTA and invasive coronary angiography. All CTA scans were evaluated for the presence of obstructive coronary stenosis by a blinded expert, and results were compared with quantitative coronary angiography. Four patients were excluded from initial analysis due to non-diagnostic image quality. Sensitivity, specificity, and positive and negative predictive values to detect ≥50% luminal narrowing on a patient basis were 100, 88, 92, and 100%, respectively. Moreover, sensitivity, specificity, and positive and negative predictive values to detect ≥70% luminal narrowing on a patient basis were 94, 95, 88, and 98%, respectively. With inclusion of non-diagnostic imaging studies, sensitivity, specificity, and positive and negative predictive values to detect ≥50% luminal narrowing on a patient basis were 100, 81, 88, and 100%, respectively. Conclusion The current study shows that 320-row CTA allows accurate non-invasive assessment of significant CAD.
ABSTRACT
Complement activation leads primarily to membrane attack complex formation and subsequent target cell lysis. Protection against self‐damage is regulated by complement regulatory proteins, ...including CD46, CD55, and CD59. Within their promoter regions, single‐nucleotide polymorphisms (SNPs) are present that could influence transcription. We analyzed these SNPs and investigated their influence on protein expression levels. A single SNP configuration in the promoter region of CD59 was found correlating with lower CD59 expression on lung endothelial cells (p = 0.016) and monocytes (p = 0.013). Lung endothelial cells with this SNP configuration secreted more profibrotic cytokine IL‐6 (p = 0.047) and fibroblast growth factor β (p = 0.036) on exposure to sublytic complement activation than cells with the opposing configuration, whereas monocytes were more susceptible to antibody‐mediated complement lysis (p < 0.0001). Analysis of 137 lung transplant donors indicated that this CD59 SNP configuration correlates with impaired long‐term survival (p = 0.094) and a significantly higher incidence of bronchiolitis obliterans syndrome (p = 0.046) in the recipient. These findings support a role for complement in the pathogenesis of this posttransplant complication and are the first to show a deleterious association of a donor CD59 promoter polymorphism in lung transplantation.
In this study, the authors show both a functional relation between a single promotor polymorphism in the CD59 gene, protein expression, and susceptibility to complement‐mediated cell lysis, as well as a clinical relation of this genetic configuration in the donor and the risk for development of obstructive chronic lung allograft dysfunction in the recipient after lung transplantation.
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