Abstract Background Healthcare providers worldwide are struggling with rising costs while hospitals budgets are under stress. Colorectal cancer surgery is commonly performed, however it is associated ...with a disproportionate share of adverse events in general surgery. Since adverse events are associated with extra hospital costs it seems important to explicitly discuss the costs of complications and the risk factors for high-costs after colorectal surgery. Methods Retrospective analysis of clinical and financial outcomes after colorectal cancer surgery in 29 Dutch hospitals (6768 patients). Detailed clinical data was derived from the 2011–2012 population-based Dutch Surgical Colorectal Audit database. Costs were measured uniform in all participating hospitals and based on Time-Driven Activity-Based Costing. Findings Of total hospital costs in this study, 31% was spent on complications and the top 5% most expensive patients were accountable for 23% of hospitals budgets. Minor and severe complications were respectively associated with a 26% and 196% increase in costs as compared to patients without complications. Independent from other risk factors, ASA IV, double tumor, ASA III, short course preoperative radiotherapy and TNM-4 stadium disease were the top-5 attributors to high costs. Conclusions This article shows that complications after colorectal cancer surgery are associated with a substantial increase in costs. Although not all surgical complications can be prevented, reducing complications will result in considerable cost savings. By providing a business case we show that investments made to develop targeted quality improvement programs will pay off eventually. Results based on this study should encourage healthcare providers to endorse quality improvement efforts.
Surveillance of individuals at risk of developing pancreatic ductal adenocarcinoma (PDAC) has the potential to improve survival, yet early detection based on solely imaging modalities is challenging. ...We aimed to identify changes in serum glycosylation levels over time to earlier detect PDAC in high-risk individuals.
Individuals with a hereditary predisposition to develop PDAC were followed in two surveillance programs. Those, of which at least two consecutive serum samples were available, were included. Mass spectrometry analysis was performed to determine the total N-glycome for each consecutive sample. Potentially discriminating N-glycans were selected based on our previous cross-sectional analysis and relative abundances were calculated for each glycosylation feature.
165 individuals (“FPC-cohort” N = 119; Leiden cohort N = 46) were included. In total, 97 (59%) individuals had a genetic predisposition (77 CDKN2A, 15 BRCA1/2, 5 STK11) and 68 (41%) a family history of PDAC without a known genetic predisposition (>10-fold increased risk of developing PDAC). From each individual, a median number of 3 serum samples (IQR 3) was collected.
Ten individuals (6%) developed PDAC during 35 months of follow-up; nine (90%) of these patients carried a CDKN2A germline mutation. In PDAC cases, compared to all controls, glycosylation characteristics were increased (fucosylation, tri- and tetra-antennary structures, specific sialic linkage types), others decreased (complex-type diantennary and bisected glycans). The largest change over time was observed for tri-antennary fucosylated glycans, which were able to differentiate cases from controls with a specificity of 92%, sensitivity of 49% and accuracy of 90%.
Serum N-glycan monitoring may support early detection in a pancreas surveillance program.
Purpose
Scarce data are available on differences among index colectomies for colon cancer regarding reoperation for anastomotic leakage (AL) and clinical consequences. Therefore, this nationwide ...observational study aimed to evaluate reoperations for AL after colon cancer surgery and short-term postoperative outcomes for the different index colectomies.
Methods
Patients who underwent resection with anastomosis for a first primary colon carcinoma between 2013 and 2019 and were registered in the Dutch ColoRectal Audit were included. Primary outcomes were mortality, ICU admission, and stoma creation.
Results
Among 39,565 patients, the overall AL rate was 4.8% and ranged between 4.0% (right hemicolectomy) and 15.4% (subtotal colectomy). AL was predominantly managed with reoperation, ranging from 81.2% after transversectomy to 92.4% after sigmoid resection (
p
< 0.001). Median time to reoperation differed significantly between index colectomies (range 4–8 days,
p
< 0.001), with longer and comparable intervals for non-surgical reinterventions (range 13–18 days,
p
= 0.747). After reoperation, the highest mortality rates were observed for index transversectomy (15.4%) and right hemicolectomy (14.4%) and lowest for index sigmoid resection (5.6%) and subtotal colectomy (5.9%) (
p
< 0.001). Reoperation with stoma construction was associated with a higher mortality risk than without stoma construction after index right hemicolectomy (17.7% vs. 8.5%,
p
= 0.001). ICU admission rate was 62.6% overall (range 56.7–69.2%), and stoma construction rate ranged between 65.5% (right hemicolectomy) and 93.0% (sigmoid resection).
Conclusion
Significant differences in AL rate, reoperation rate, time to reoperation, postoperative mortality after reoperation, and stoma construction for AL were found among the different index colectomies for colon cancer, with relevance for patient counseling and perioperative management.
Abstract Background Availability of anastomotic leakage rates and mortality rates following anastomotic leakage is essential when informing patients with rectal cancer preoperatively. We performed a ...meta-analysis of studies describing anastomotic leakage and the subsequent postoperative mortality in relation to the overall postoperative mortality after low anterior resection for rectal cancer. Methods A systematic search was performed of the published literature. Data on the definition and incidence rate of AL, postoperative mortality caused by AL, and overall postoperative mortality were extracted. Data were pooled and a meta-analysis was performed. Results Twenty-two studies with 10,343 patients in total were analyzed. Meta-analysis of the data showed an average AL rate of 9%, postoperative mortality caused by leakage of 0.7% and overall postoperative mortality of 2%. The studies showed variation in incidence, definition and measurement of all outcomes. Conclusion We found a considerable overall AL rate and a large contribution of AL to the overall postoperative mortality. The variability of definitions and measurement of AL, postoperative mortality caused by leakage and overall postoperative mortality may hinder providing reliable risk information. Large-scale audit programs may provide accurate and valid risk information which can be used for preoperative decision making.
The tumor‐stroma ratio (TSR) has proven to be a strong prognostic factor in breast cancer, demonstrating better survival for patients with stroma‐low tumors. Since the role of the TSR as a predictive ...marker for neoadjuvant chemotherapy outcome is yet unknown, this association was evaluated for HER2‐negative breast cancer in the prospective DIRECT and NEOZOTAC trials. The TSR was assessed on 375 hematoxylin and eosin‐stained sections of pre‐treatment biopsies. Associations between the TSR and chemotherapy response according to the Miller‐Payne (MP) grading system, and between the TSR and pathological response were examined using Pearson's chi‐square, Cochran‐Armitage test for trend and regression analyses. A stroma‐low tumor prior to neoadjuvant chemotherapy was significantly associated with a higher MP score (P = .005). This relationship remained significant in the estrogen receptor (ER)‐negative subgroup (P = .047). The univariable odds ratio (OR) of a stroma‐low tumor on pathological complete response (pCR) was 2.46 (95% CI 1.34‐4.51, P = .004), which attenuated to 1.90 (95% CI 0.85‐4.25, P = .119) after adjustment for relevant prognostic factors. Subgroup analyses revealed an OR of 5.91 in univariable analyses for ER‐negativity (95% CI 1.19‐29.48, P = .030) and 1.48 for ER‐positivity (95% CI 0.73‐3.01, P = .281). In conclusion, a low amount of stroma on pre‐treatment biopsies is associated with a higher MP score and pCR rate. Therefore, the TSR is a promising biomarker in predicting neoadjuvant treatment outcome. Incorporating this parameter in routine pathological diagnostics could be worthwhile to prevent overtreatment and undertreatment.
Background
Postpancreatectomy haemorrhage (PPH) and venous thromboembolism (VTE) are serious complications following pancreatic surgery. The aim was to assess the timing, occurrence and predictors of ...PPH and VTE.
Methods
Elective pancreatic resections undertaken in a single university hospital between November 2013 and September 2017 were assessed. Three intervals were reviewed, each with a different routine regimen of nadroparin: 2850 units once daily (single dose) administered in hospital only, or 5700 units once daily (double dose) or 2850 units twice daily (split dose) administered in hospital and continued for 6 weeks after surgery. Clinically relevant PPH (CR‐PPH) was classified according to International Study Group of Pancreatic Surgery criteria. VTE was defined according to a number of key diagnostic criteria within 6 weeks of surgery. Cox regression analyses were performed to test the hypotheses that the double‐dose group would experience more PPH than the other two groups, the single‐dose group would experience more VTE than the other two groups, and the split‐dose group would experience the fewest adverse events (PPH or VTE).
Results
In total, 240 patients were included, 80 per group. The double‐dose group experienced significantly more CR‐PPH (hazard ratio (HR) 2·14, 95 per cent c.i. 1·16 to 3·94; P = 0·015). More relaparotomies due to CR‐PPH were performed in the double‐dose group (16 versus 3·8 per cent; P = 0·002). The single‐dose group did not experience more VTE (HR 1·41, 0·43 to 4·62; P = 0·570). The split dose was not associated with fewer adverse events (HR 0·77, 0·41 to 1·46; P = 0·422). Double‐dose low molecular weight heparin (LMWH), high BMI and pancreatic fistula were independent predictors of CR‐PPH.
Conclusion
A double dose of LMWH prophylaxis continued for 6 weeks after pancreatic resection was associated with a twofold higher rate of CR‐PPH, resulting in four times more relaparotomies. Patients receiving a single daily dose of LMWH in hospital only did not experience a higher rate of VTE.
Three different low molecular weight heparin in‐hospital regimens were reviewed retrospectively: once‐daily 2850 units (single dose), once‐daily 5700 units (double dose) or twice‐daily 2850 units (split dose) of nadroparin. A double dose was independently associated with a twofold higher rate of clinically relevant postpancreatectomy haemorrhage, necessitating a fourfold higher relaparotomy rate. A single dose did not appear to increase the venous thromboembolism rate.
Once daily single dose of low molecular weight heparin prophylaxis in hospital best
The transforming growth factor-β (TGF-β) pathway has dual effects on tumor growth. Seemingly, discordant results have been published on the relation between TGF-β signaling markers and prognosis in ...breast cancer. Improved prognostic information for breast cancer patients might be obtained by assessing interactions among TGF-β signaling biomarkers.
The expression of nuclear Smad4, nuclear phosphorylated-Smad2 (p-Smad2), and the membranous expression of TGF-β receptors I and II (TβRI and TβRII) was determined on a tissue microarray of 574 breast carcinomas. Tumors were stratified according to the Smad4 expression in combination with p-Smad2 expression or Smad4 in combination with the expression of both TGF-β receptors.
Tumors with high expression of TβRII, TβRI and TβRII, and p-Smad2 (P = 0.018, 0.005, and 0.022, respectively), and low expression of Smad4 (P = 0.005) had an unfavorable prognosis concerning progression-free survival. Low Smad4 expression combined with high p-Smad2 expression or low expression of Smad4 combined with high expression of both TGF-β receptors displayed an increased hazard ratio of 3.04 95% confidence interval (CI) 1.390–6.658 and 2.20 (95% CI 1.464–3.307), respectively, for disease relapse.
Combining TGF-β biomarkers provides prognostic information for patients with stage I–III breast cancer. This can identify patients at increased risk for disease recurrence that might therefore be candidates for additional treatment.
Several studies have assessed the concordance of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status between core needle biopsy (CNB) and resection specimens, usually in ...small patient series and with discordant results.
ER and HER2 status determined on CNB and tissue micro-arrays of resected tumors were compared for patients treated at the Leiden University Medical Center (LUMC). When results were discordant, whole-sized slides were analyzed. Additionally, literature was searched for published patient series and combined with our data to assess the concordance of ER and HER2 determination between CNB and resection specimens.
In the LUMC series, concordance for ER status was 99.1%. Combined concordance from 20 studies and the LUMC patient series was 93.7%. For HER2 testing, concordance was 96.2% for patients in the LUMC series. Our study and three others have investigated the concordance when HER2 was determined according to the American Society of Clinical Oncology and College of Pathology guidelines and overall concordance was 97.8%.
Concordance between CNB and surgical specimens was high for both ER and HER2 testing. However, we recommend retesting ER-negative CNB results on the surgical specimen and performing in situ hybridization assays on HER2 immunohistochemistry 3+ CNBs to confirm HER2 status.
Therapy resistance is a known problem in breast cancer and is associated with a variety of mechanisms. The role of the tumor microenvironment in cancer development and resistance mechanisms is ...becoming increasingly understood. Tumor–stroma is the main component of the tumor microenvironment. Stromal cells like cancer-associated fibroblasts (CAFs) are believed to contribute to chemotherapy resistance via the production of several secreted factors like cytokines and chemokines. CAFs are found to influence disease progression; patients with primary tumors with a high amount of tumor–stroma have a significantly worse outcome. Therefore the role of CAFs resistance mechanisms makes them a promising target in anti-cancer therapy. An overview of recent advances in strategies to target breast cancer stroma is given and the current literature regarding these stromal targets is discussed. CAF-specific proteins as well as secreted molecules involved in tumor–stroma interactions provide possibilities for stroma-specific therapy. The development of stroma-specific therapy is still in its infancy and the available literature is limited. Within the scope of personalized treatment, biomarkers based on the tumor–stroma have future potential for the improvement of treatment via image-guided surgery (IGS) and PET scanning.
A newly developed analytical strategy was applied to profile the total serum
-glycome of 64 colorectal cancer (CRC) patients before and after surgical intervention. In this cohort, it was previously ...found that serum
-glycome alterations in CRC were associated with patient survival. Here, fluorescent labeling of serum
-glycans was applied using procainamide and followed by sialic acid derivatization specific for α2,6- and α2,3-linkage types via ethyl esterification and amidation, respectively. This strategy allowed efficient separation of specific positional isomers on reversed-phase liquid chromatography-fluorescence detection-mass spectrometry (RPLC-FD-MS) and complemented the previous glycomics data based on matrix-assisted laser desorption/ionization (MALDI)-MS that did not include such separations. The results from comparing pre-operative CRC to post-operative samples were in agreement with studies that identified a decrease in di-antennary structures with core fucosylation and an increase in sialylated tri- and tetra-antennary
-glycans in CRC patient sera. Pre-operative abundances of
-glycans showed good performance for the classification of adenocarcinoma and led to the revisit of the previous MALDI-MS dataset with regard to histological and clinical data. This strategy has the potential to monitor patient profiles before, during, and after clinical events such as treatment, therapy, or surgery and should also be further explored.
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