| 1. |
- Busweiler, L A D, et al.
(författare)
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International benchmarking in oesophageal and gastric cancer surgery
- 2019
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Ingår i: BJS Open. - : Oxford University Press (OUP). - 2474-9842. ; 3:1, s. 62-73
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Tidskriftsartikel (refereegranskat)abstract
- Background: Benchmarking on an international level might lead to improved outcomes at a national level. The aim of this study was to compare treatment and surgical outcome data from the Swedish National Register for Oesophageal and Gastric Cancer (NREV) and the Dutch Upper Gastrointestinal Cancer Audit (DUCA).Methods: All patients with primary oesophageal or gastric cancer who underwent a resection and were registered in NREV or DUCA between 2012 and 2014 were included. Differences in 30-day mortality were analysed using case mix-adjusted multivariable logistic regression.Results: In total, 4439 patients underwent oesophagectomy (2509 patients) or gastrectomy (1930 patients). Estimated resection rates were comparable. Swedish patients were older but had less advanced disease and less co-morbidity than Dutch patients. Neoadjuvant treatment rates were lower in Sweden than in the Netherlands, both for patients who underwent oesophagectomy (68·6 versus 90·0 per cent respectively; P < 0·001) and for those having gastrectomy (38·3 versus 56·6 per cent; P < 0·001). In Sweden, transthoracic oesophagectomy was performed in 94·7 per cent of patients, whereas in the Netherlands, a transhiatal approach was undertaken in 35·8 per cent. Higher annual procedural volumes per hospital were observed in the Netherlands. Adjusted 30-day and/or in-hospital mortality after gastrectomy was statistically significantly lower in Sweden than in the Netherlands (odds ratio 0·53, 95 per cent c.i. 0·29 to 0·95).Conclusion: For oesophageal and gastric cancer, there are differences in patient, tumour and treatment characteristics between Sweden and the Netherlands. Postoperative mortality in patients with gastric cancer was lower in Sweden.
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| 2. |
- Kumagai, K., et al.
(författare)
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Survival benefit and additional value of preoperative chemoradiotherapy in resectable gastric and gastro-oesophageal junction cancer : A direct and adjusted indirect comparison meta-analysis
- 2015
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 41:3, s. 282-294
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Forskningsöversikt (refereegranskat)abstract
- Several phase I/II studies of chemoradiotherapy for gastric cancer have reported promising results, but the significance of preoperative radiotherapy in addition to chemotherapy has not been proven. In this study, a systematic literature search was performed to capture survival and postoperative morbidity and mortality data in randomised clinical studies comparing preoperative (chemo)radiotherapy or chemotherapy versus surgery alone, or preoperative chemoradiotherapy versus chemotherapy for gastric and/or gastro-oesophageal junction (GOJ) cancer. Hazard ratios (HRs) for overall mortality were extracted from the original studies, individual patient data provided from the principal investigators of eligible studies or the earlier published meta-analysis. The incidences of postoperative morbidities and mortalities were also analysed. In total 18 studies were eligible and data were available from 14 of these. The meta-analysis on overall survival yielded HRs of 0.75 (95% CI 0.65-0.86, P < 0.001) for preoperative (chemo)radiotherapy and 0.83 (95% CI 0.67-1.01, P = 0.065) for preoperative chemotherapy when compared to surgery alone. Direct comparison between preoperative chemoradiotherapy and chemotherapy resulted in an HR of 0.71 (95% CI 0.45-1.12, P = 0.146). Combination of direct and adjusted indirect comparisons yielded an HR of 0.86 (95% CI 0.69-1.07, P = 0.171). No statistically significant differences were seen in the risk for postoperative morbidity or mortality between preoperative treatments and surgery alone, or preoperative (chemo)radiotherapy and chemotherapy. Preoperative (chemo)radiotherapy for gastric and GOJ cancer showed significant survival benefit over surgery alone. In comparisons between preoperative chemotherapy and (chemo)radiotherapy, there is a trend towards improved survival when adding radiotherapy, without increased postoperative morbidity or mortality.
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| 3. |
- Budeus, B., et al.
(författare)
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Human cord blood b cells differ from the adult counterpart by conserved ig repertoires and accelerated response dynamics
- 2021
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 206:12, s. 2839-2851
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Tidskriftsartikel (refereegranskat)abstract
- Neonatal and infant immune responses are characterized by a limited capability to generate protective Ab titers and memory B cells as seen in adults. Multiple studies support an immature or even impaired character of umbilical cord blood (UCB) B cells themselves. In this study, we provide a comprehensive molecular and functional comparison of B cell subsets from UCB and adult peripheral blood. Most UCB B cells have a mature, naive B cell phenotype as seen in adults. The UCB Ig repertoire is highly variable but interindividually conserved, as BCR clonotypes are frequently shared between neonates. Furthermore, UCB B cells show a distinct transcriptional program that confers accelerated responsiveness to stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into Ab-secreting cells, presumably limiting memory B cell formation. Humanized mice suggest that the distinctness of UCB versus adult B cells is already reflected by the developmental program of hematopoietic precursors, arguing for a layered B-1/B-2 lineage system as in mice, albeit our findings suggest only partial comparability to murine B-1 cells. Our study shows that UCB B cells are not immature or impaired but differ from their adult mature counterpart in a conserved BCR repertoire, efficient IgA class switching, and accelerated, likely transient response dynamics. © 2021 by TheAmericanAssociation of Immunologists, Inc.
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| 4. |
- Stockfelt, Marit, et al.
(författare)
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Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis-a spin-off study of the NORD-STAR randomized clinical trial
- 2021
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFN alpha have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFN alpha protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. Results IFN alpha protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFN alpha protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFN alpha protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. Conclusion IFN alpha protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFN alpha positivity did not predict remission in any of the treatment arms, suggesting that the IFN alpha system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, .
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| 5. |
- Baldaque-Silva, F., et al.
(författare)
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Impact of gastroesophageal reflux control through tailored proton pump inhibition therapy or fundoplication in patients with Barrett's esophagus
- 2017
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 23:17, s. 3174-3183
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Tidskriftsartikel (refereegranskat)abstract
- AIM To determine the impact of upwards titration of proton pump inhibition (PPI) on acid reflux, symptom scores and histology, compared to clinically successful fundoplication. Two cohorts of long-segment Barrett's esophagus (BE) patients were studied. In group 1 (n = 24), increasing doses of PPI were administered in 8-wk intervals until acid reflux normalization. At each assessment, ambulatory 24 h pH recording, endoscopy with biopsies and symptom scoring (by a gastroesophageal reflux disease health related quality of life questionnaire, GERD/HRLQ) were performed. Group 2 (n = 30) consisted of patients with a previous fundoplication. In group 1, acid reflux normalized in 23 of 24 patients, resulting in improved GERD/HRQL scores (P = 0.001), which were most pronounced after the starting dose of PPI (P < 0.001). PPI treatment reached the same level of GERD/HRQL scores as after a clinically successful fundoplication (P = 0.5). Normalization of acid reflux in both groups was associated with reduction in papillary length, basal cell layer thickness, intercellular space dilatation, and acute and chronic inflammation of squamous epithelium. This study shows that acid reflux and symptom scores co-vary throughout PPI increments in long-segment BE patients, especially after the first dose of PPI, reaching the same level as after a successful fundoplication. Minor changes were found among GERD markers at the morphological level.
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| 6. |
- Scarpellini, E., et al.
(författare)
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International consensus on the diagnosis and management of dumping syndrome
- 2020
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Ingår i: Nature Reviews Endocrinology. - : Springer Science and Business Media LLC. - 1759-5029 .- 1759-5037. ; 16:8
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Tidskriftsartikel (refereegranskat)abstract
- Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose. Dumping syndrome is a frequent complication of oesophageal and gastric surgery, as well as bariatric surgery; however, guidance on how to manage patients with this condition is lacking. In this Evidence-based guideline, the authors use a Delphi consensus process to develop uniform guidance for the definition, diagnosis and management of dumping syndrome.
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| 7. |
- Lund, M, et al.
(författare)
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Nitric oxide and endothelin-1 release after one-lung ventilation during thoracoabdominal esophagectomy.
- 2013
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Ingår i: Diseases of the esophagus. - : Oxford University Press (OUP). - 1120-8694. ; 26:8, s. 853-858
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Tidskriftsartikel (refereegranskat)abstract
- One-lung ventilation (OLV) is applied during esophagectomy to improve exposure during the thoracic part of the operation. Collapse of lung tissue, shunting of pulmonary blood flow, and changes in alveolar oxygenation during and after OLV may possibly induce an ischemia-reperfusion response in the lung, which may affect the pulmonary endothelium. Such a reaction might thereby contribute to the frequently occurring respiratory complications among these patients. In this small trial, 30 patients were randomized to either OLV (n= 16) or two-lung ventilation (TLV, n= 14) during esophagectomy. Central venous and arterial plasma samples were taken before and after OLV/TLV for analysis of nitrite and a metabolite of nitric oxide (NO), and also during the 1st, 2nd, 3rd, and 10th postoperative day for analysis of endothelin, another endothelium-derived vasoactive mediator. Lung biopsies were taken before and after OLV or TLV, and analyzed regarding immunofluorescence for isoform of NO synthase, a protein upregulated during inflammatory response and also vascular congestion. No changes in lung isoform of NO synthase immunofluorescence or vascular congestion were registered after neither OLV nor TLV. Plasma nitrite and endothelin levels were similar in the two study groups. We conclude that OLV does not seem to have any influence on key regulators of pulmonary vascular tone and inflammation, i.e. NO and endothelin. From this perspective, OLV seems to be a safe method, which defends its clinical position to facilitate surgical exposure during thoracoabdominal esophagectomy.
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| 8. |
- Ericson, J, et al.
(författare)
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Large-diameter (30-35 mm) pneumatic balloon dilatation of the pylorus in patients with gastric outlet obstruction symptoms after esophagectomy
- 2013
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Ingår i: Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. - : SAGE Publications. - 1799-7267. ; 102:2, s. 83-86
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Tidskriftsartikel (refereegranskat)abstract
- Functional gastric outlet obstruction is a common problem after esophagectomy. The aim of this study was to evaluate the safety and efficacy of treating this group of patients with pneumatic dilatation of the pyloric sphincter region using a large-diameter (30–35 mm) balloon. Material and Methods: A review of all patients who had undergone pneumatic dilatation of the pylorus sphincter because of gastric outlet obstruction symptoms after esophagectomy at the Karolinska University Hospital from 2006–2011 was completed. Main outcomes were recordings of nausea, regurgitation and bloating. Results: A total of 13 patients received pneumatic dilatation after an esophagectomy. The median time between esophagectomy and the first dilatation was 100 days, and the patients underwent a total of 21 dilatations (1–3 per patient) to a final median diameter of 30 mm. No procedure-related complications occurred. The median follow-up time was 205 days, and nausea and regurgitation improved significantly (p < 0.001, Fisher’s test). Conclusions: Pneumatic dilatation of the pylorus using a large-diameter pneumatic balloon seems to be a safe and effective method for treating symptoms suggestive of gastric outlet obstruction after esophagectomy. To document its true effectiveness, a randomized and sham-controlled study is needed.
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| 9. |
- Insulander, J., et al.
(författare)
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Prognosis following surgical bypass compared with laparotomy alone in unresectable pancreatic adenocarcinoma
- 2016
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Ingår i: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 103:9, s. 1200-1208
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Tidskriftsartikel (refereegranskat)abstract
- Background: Resection with curative intent has been shown to prolong survival of patients with locoregional pancreatic ductal adenocarcinoma (PDAC). However, up to 33 per cent of patients are deemed unresectable at exploratory laparotomy owing to unanticipated locally advanced or metastatic disease. In these patients, prophylactic double bypass (PDB) procedures have been considered the standard of care. The aim of this study was to compare PDB with exploratory laparotomy alone in terms of impact on postoperative course, chemotherapy and overall survival.Methods: This retrospective observational cohort study (2004-2013) was conducted using a prospective institutional database. Patients with histologically confirmed, unresectable PDAC were included. Relationships between PDB procedures, exploratory laparotomy alone, postoperative chemotherapy and best supportive care were investigated by means of Cox regression. Overall survival was compared using Kaplan-Meier estimations and log rank test.Results: Of 503 patients with PDAC scheduled for resection with curative intent, 104 were deemed unresectable at laparotomy (resection rate 79·3 per cent). Seventy-four patients underwent PDB procedures and 30 had exploratory laparotomy alone. PDB and exploratory laparotomy were similar in terms of perioperative mortality, initiation of chemotherapy and overall survival. Compared with best supportive care, postoperative chemotherapy prolonged survival (8·0 versus 14·4 months in locally advanced PDAC, P = 0·007; 2·3 versus 8·0 months in metastatic PDAC, P < 0·001). Patients undergoing chemotherapy following exploratory laparotomy alone had longer median overall survival than patients undergoing chemotherapy following PDB procedures (16·3 versus 10·3 months; P = 0·040).Conclusion: Patients with pancreatic cancer deemed unresectable at laparotomy may derive survival benefit from subsequent chemotherapy as opposed to supportive care alone. At laparotomy, proceeding with a bypass procedure for prophylactic symptom control may be prognostically unfavourable.
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| 10. |
- Klevebro, F., et al.
(författare)
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Morbidity and mortality after surgery for cancer of the oesophagus and astro-oesophageal junction : a randomized clinical trial of neoadjuvant hemotherapy vs. neoadjuvant chemoradiation
- 2015
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 41:7, s. 920-926
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the incidence and severity of postoperative omplications after oesophagectomy for carcinoma of the oesophagus and astro-oesophageal junction (GOJ) after randomized accrual to eoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT). ackground: Neoadjuvant therapy improves long-term survival after esophagectomy. To date, evidence is insufficient to determine whether ombined nCT, or nCRT alone, is the most beneficial. ethods: Patients with carcinoma of the oesophagus or GOJ, resectable ith a curative intention, were enrolled in this multicenter trial onducted at seven centres in Sweden and Norway. Study participants re andomized to nCT or nCRT followed by surgery with two-field ymphadenectomy. Three cycles of cisplatin/5-fluorouracil was dministered in all patients, while 40 Gy of concomitant radiotherapy as administered in the nCRT group. esults: Of the randomized 181 patients, 91 were assigned to nCT and 90 o nCRT. One-hundred-and-fifty-five patients, 78 nCT and 77 nCRT, nderwent resection. There was no statistically significant difference etween the groups in the incidence of surgical or nonsurgical omplications (P-value = 0.69 and 0.13, respectively). There was no 0-day mortality, while the 90-day mortality was 3% (2/78) in the nCT roup and 6% (5/77) in the nCRT group (P = 0.24). The median lavien-Dindo complication severity grade was significantly higher in he nCRT. group (P = 0.001). onclusion: There was no significant difference in the incidence of omplications between patients randomized to nCT and nCRT. However, omplications were significantly more severe after nCRT. Registration rial database: The trial was registered in the Clinical Trials tabase registration number NCT01362127).
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