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Purpose The extended role of breast-conserving surgery (BCS) in the neoadjuvant setting may raise concerns on the oncologic safety of BCS compared to mastectomy. This study compared long-term outcomes after neoadjuvant chemotherapy (NAC) between patients treated with BCS and mastectomy. Methods All breast cancer patients treated with NAC from 2008 until 2017 at the Amphia Hospital (the Netherlands) were included. Disease-free and overall survival were compared between BCS and mastectomy with survival functions. Multivariable Cox proportional hazard regression was performed to determine prognostic variables for disease-free survival. Results 561 of 612 patients treated with NAC were eligible: 362 (64.5%) with BCS and 199 (35.5%) with mastectomy. Median follow-up was 6.8 years (0.9–11.9). Mastectomy patients had larger tumours and more frequently node-positive or lobular cancer. Unadjusted five-year disease-free survival was 90.9% for BCS versus 82.9% for mastectomy (p = .004). Unadjusted five-year overall survival was 95.3% and 85.9% (p p = .019) and triple negative disease (HR 5.946, 95% CI 2.703–13.081, p p = .027) and axilla (HR 0.332, 95% CI 0.193–0.572, p = .001) were positive predictors for disease-free survival. Mastectomy versus BCS was not a significant predictor for disease-free survival when adjusted for the former variables (unadjusted HR 2.13 (95%CI: 1.4–3.24), adjusted HR 1.31 (95%CI: 0.81–2.13)). In the BCS group, disease-free and overall survival did not differ significantly between cT1, cT2 or cT3 tumours. Conclusion BCS does not impair disease-free and overall survival in patients treated with NAC. Tumour biology and treatment response are significant prognostic indicators.

The long-term outcomes of surgery followed by delirium after multimodal prehabilitation program are largely unknown. We conducted this study to assess the effects of prehabilitation on 1-year mortality and of postoperative delirium on 1-year mortality and functional outcomes. The subjects of this study were patients aged ≥ 70 years who underwent elective surgery for abdominal aortic aneurysm (AAA) or colorectal cancer (CRC) between January 2013, and June 2018. A prehabilitation program was implemented in November 2015, which aimed to optimize physical health, nutritional status, factors of frailty and preoperative anemia prior to surgery. The outcomes were assessed as mortality after 6 and 12 months, compared between the two treatment groups; and mortality and functional outcomes, compared between patients with and those without delirium. There were 627 patients (controls N = 360, prehabilitation N = 267) included in this study. Prehabilitation did not reduce mortality after 1 year (HR 1.31 [95% CI 0.75–2.30]; p = 0.34). Delirium was significantly associated with 1-year mortality (HR 4.36 [95% CI 2.45–7.75]; p

Background Prehabilitation programs have recently been suggested as potentially able to lower the incidence of delirium in elderly patients undergoing major abdominal surgery. For these prehabilitation programs to become successful, it is essential to identify those patients who are most likely to develop a delirium. Material and methods A single-centre cohort study was conducted. Inclusion criteria were: age ≥70 years and scheduled for abdominal surgery for colorectal cancer or an abdominal aortic aneurysm between January 2013 and June 2018. Baseline patient, surgical, anaesthesiologic and haematological characteristics were collected. A risk factor analysis was conducted, with postoperative delirium as primary outcome, by performing a multivariable logistic regression analysis. Results In this study, 627 patients were included, of whom 64 (10%) developed a delirium. Variables that differed significantly between delirious and non-delirious patients were age, burden of comorbidity, renal impairment, hypertension, cognitive impairment, history of delirium, physical and nutritional impairment, open surgery, preoperative anaemia and erythrocyte transfusion. After multivariable logistic regression analysis, risk factors for postoperative delirium after major abdominal surgery were renal impairment (OR 2.2; 95%CI 1.2–4.3), cognitive impairment (OR 4.1; 95%CI 1.8–9.2), an ASA score ≥ 3 (OR 2.0; 95% CI 1.0–3.9), being an active smoker (OR 2.7; 95%CI 1.3–5.8), ICU admission (OR 7.1; 95%CI 3.5–14.3), erythrocyte transfusion (OR 2.4; 95%CI 1.2–4.9) and a diagnosis of colorectal cancer (CRC); (OR 4.0; 95% CI 1.7–9.6). Prehabilitation had a protective effect (OR 0.5; 95% CI 0.3–0.9). Conclusion Postoperative delirium is a frequent complication after major abdominal surgery in the elderly, especially in octogenarians and after open procedures. Renal impairment, cognitive impairment, being an active smoker, ICU admission, erythrocyte transfusion and a diagnosis of CRC are important risk factors for the development of delirium. Prehabilitation lowers the risk of developing a delirium.

BACKGROUND: Due to the increase in elderly patients who undergo major abdominal surgery there is a subsequent increase in postoperative complications, prolonged hospital stays, health-care costs and mortality rates. Delirium is a frequent and severe complication in the 'frail' elderly patient. Different preoperative approaches have been suggested to decrease incidence of delirium by improving patients' baseline health. Studies implementing these approaches are often heterogeneous, have a small sample and do not provide high-quality or successful strategies. The aim of this study is to prevent postoperative delirium and other complications by implementing a unique multicomponent and multidisciplinary prehabilitation program. METHODS: This is a single-center controlled before-and-after study. Patients aged ≥70 years in need of surgery for colorectal cancer or an abdominal aortic aneurysm are considered eligible. Baseline characteristics (such as factors of frailty, physical condition and nutritional state) are collected prospectively. During 5 weeks prior to surgery, patients will follow a prehabilitation program to optimize overall health, which includes home-based exercises, dietary advice and intravenous iron infusion in case of anaemia. In case of frailty, a geriatrician will perform a comprehensive geriatric assessment and provide additional preoperative interventions when deemed necessary. The primary outcome is incidence of delirium. Secondary outcomes are length of hospital stay, complication rate, institutionalization, 30-day, 6- and 12-month mortality, mental health and quality of life. Results will be compared to a retrospective control group, meeting the same inclusion and exclusion criteria, operated on between January 2013 and October 2015. Inclusion of the prehabilitation cohort started in November 2015; data collection is ongoing. DISCUSSION: This is the first study to investigate the effect of prehabilitation on postoperative delirium. The aim is to provide evidence, based on a large sample size, for a standardized multicomponent strategy to improve patients' preoperative physical and nutritional status in order to prevent postoperative delirium and other complications. A multimodal intervention was implemented, combining physical, nutritional, mental and hematinic optimization. This research involves a large cohort, including patients most at risk for postoperative adverse outcomes. TRIAL REGISTRATION: The protocol is retrospectively registered at the Netherlands National Trial Register (NTR) number: NTR5932 . Date of registration: 05-04-2016. ispartof: BMC GERIATRICS vol:19 issue:1 ispartof: location:England status: published

BackgroundPostoperative ileus is a common complication of abdominal surgery, leading to patient discomfort, morbidity and prolonged postoperative length of hospital stay (LOS). Previous studies suggested that chewing gum stimulates bowel function after abdominal surgery, but were underpowered to evaluate its effect on LOS and did not include enhanced recovery after surgery (ERAS)-based perioperative care. This study evaluated whether chewing gum after elective abdominal surgery reduces LOS and time to bowel recovery in the setting of ERAS-based perioperative care.MethodsA multicentre RCT was performed of patients over 18 years of age undergoing abdominal surgery in 12 hospitals. Standard postoperative care (control group) was compared with chewing gum three times a day for 30 min in addition to standard postoperative care. Randomization was computer-generated; allocation was concealed. The primary outcome was postoperative LOS. Secondary outcomes were time to bowel recovery and 30-day complications.ResultsBetween 2011 to 2015, 1000 patients were assigned to chewing gum and 1000 to the control arm. Median LOS did not differ: 7 days in both arms (P = 0·364). Neither was any difference found in time to flatus (24 h in control group versus 23 h with chewing gum; P = 0·873) or time to defaecation (60 versus 52 h respectively; P = 0·562). The rate of 30-day complications was not significantly different either.ConclusionThe addition of chewing gum to an ERAS postoperative care pathway after elective abdominal surgery does not reduce the LOS, time to bowel recovery or the rate of postoperative complications. Registration number: NTR2594 (Netherlands Trial Register).

BackgroundDelirium is a common and serious complication in elderly patients undergoing major abdominal surgery, with significant adverse outcomes. Successful strategies or therapies to reduce the incidence of delirium are scarce. The objective of this study was to assess the role of prehabilitation in reducing the incidence of delirium in elderly patients.MethodsA single-center uncontrolled before-and-after study was conducted, including patients aged 70 years or older who underwent elective abdominal surgery for colorectal carcinoma or an abdominal aortic aneurysm between January 2013 and October 2015 (control group) and between November 2015 and June 2018 (prehabilitation group). The prehabilitation group received interventions to improve patients' physical health, nutritional status, factors of frailty and preoperative anaemia prior to surgery. The primary outcome was incidence of delirium, diagnosed with the DSM-V criteria or the confusion assessment method. Secondary outcomes were additional complications, length of stay, unplanned ICU admission, length of ICU stay, readmission rate, institutionalization, and in-hospital or 30-day mortality.ResultA total of 360 control patients and 267 prehabilitation patients were included in the final analysis. The mean number of prehabilitation days was 39 days. The prehabilitation group had a higher burden of comorbidities and was more physically and visually impaired at baseline. At adjusted logistic regression analysis, delirium incidence was reduced significantly from 11.7 to 8.2% (OR 0.56; 95% CI 0.32-0.98; P = 0.043). No statistically significant effects were seen on secondary outcomes.ConclusionCurrent prehabilitation program is feasible and safe, and can reduce delirium incidence in elderly patients undergoing elective major abdominal surgery. This program merits further evaluation.Trial registrationDutch Trial Registration, NTR5932.

To evaluate the routine postoperative fluid management in relation to the British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients 2008 by the assessment of the fluid overload and electrolyte disorders in patients who were postoperatively treated according to an ‘enhanced recovery after surgery’ (ERAS) protocol. All liver, pancreatic and gastrointestinal surgical patients treated during a 10-week period were consecutively included in this analysis. All patients were treated according to a fast track protocol. Fluid balance charts and electrolyte disorders were recorded. Electrolyte disorders were reported based on the laboratory results. A total of 71 patients with an uncomplicated postoperative course were analysed. Even with restrictive fluid management performed as part of the ERAS protocol, hypervolemia developed in 54 % of all patients on the first postoperative day. There were no cases of excessive peripheral or pulmonary oedema in cases with excessive fluid administration. Twenty-six percent of the patients had electrolyte imbalances, euvolaemia was seen in 22 %, and 85 % of these patients had hypokalemia. Postoperative registration of fluid charts is difficult, which results in incomplete charts. This has resulted in more attention being paid to recording the fluid balance at our institution. Concerning electrolyte disorders, we recommend prophylactic potassium administration. However, there is no reason to replace standard 0.9 % NaCl/glucose 5 % by Ringer’s lactate, as the British guidelines advice.

To assess the frailty and the incidence of delirium in elderly patients undergoing elective and acute colorectal surgery in correlation with morbidity and mortality.Patients aged 65 years and older having elective and acute colorectal surgery, between April 2013 and December 2013 were included in a prospective database. Patients diagnosed with a colorectal carcinoma or diverticulitis who were operated on were included. Factors that characterize frailty of patients were noted. The incidence rates of delirium after elective and acute surgery were recorded. Delirium was diagnosed using the Delirium Observation Screening Scale (DOSS). Preoperative evaluation, surgical outcome including morbidity, hospital stay and mortality were analyzed.Patients ≥ 65 years were included, 83 (75%) received elective and 28 (25%) acute surgery. The overall incidence of delirium was 21%, 18% for elective and 29% for patients having urgent surgery (p = 0.24). Patients with delirium were older than the non-delirious patients (median 82 years vs. 74 years; p0.001). Delirious patients showed higher incidence of adverse events. Hospital stay, mortality and discharge to a nursing home were significant higher in the delirious compared to the non-delirious group (p = 0.01; 0.01; 0.02 respectively).High incidence of delirium was found in both acute and elective colorectal surgery. Delirium was associated with adverse outcomes.

Item does not contain fulltext INTRODUCTION: The objective of this study was to conduct a multicentre data analysis to identify prognostic factors for developing an axillary recurrence (AR) after negative sentinel lymph node biopsy (SLNB) in a large cohort of breast cancer patients with long follow-up. PATIENTS AND METHODS: The prospective databases from different hospitals of clinically node negative breast cancer patients operated on between, 2000 and 2002 were analyzed. SLNB was performed and pathological analysis done by local pathologists according to national guidelines. Adjuvant treatment was given according to contemporary guidelines. Multivariate analysis was performed using all available variables, a p-value of

In order to study the growth kinetics of breast tumours during long-term hormonal withdrawal, we developed a transplantable, invasive mammary carcinoma EMR-86 that originated in a female WAG/Olac rat bearing a subcutaneously implanted oestrogen pellet (EP). Outgrowth of transplanted tumours occurs only in the presence of an EP, and metastases are formed in lungs and regional lymph nodes. Subsequent EP removal induces rapid regression. However, tumours do not disappear completely, as small nodules persist. These dormant tumour remnants can be restimulated even after long periods. Because EP-stimulated tumours regressed after treatment with bromocriptine and dormant tumours in non-oestrogenized rats grew out after treatment with perphenazine, prolactin is the major growth-stimulating hormone in this model. Cell kinetics in the growing, regressing and dormant phase were studied by immunocytochemical detection of DNA-incorporated bromodeoxyuridine (BrdUrd) in tissue sections. BrdUrd labelling indices decreased from 21.6 +/- 3.0% to less than 1% within 7 days after EP removal. After prolonged hormonal withdrawal (up to 90 days) BrdUrd-labelled tumour cells could always be demonstrated (range 0.4-0.8%), without a concomitant increase in tumour volume. Additional treatment either with bromocriptine or with ovariectomy could not significantly reduce this residual proliferative activity, as demonstrated by continuous BrdUrd labelling experiments. The results indicate that in vivo dormancy may represent a steady state of cell division and cell loss, rather than an accumulation of cells in a non-cycling G0 state. Images Figure 2

Growth of the transplantable EMR-86 rat mammary carcinoma depends on elevated prolactin levels which are induced by oestrogenic stimulation of the pituitary. We investigated histological and cell kinetic changes during tumour regression after removal of implanted oestrogen pellets (EP), and we especially focused on the role of apoptosis. After EP removal, serum prolactin decreased to basal levels in 5 days, reaching its largest depletion during the first day. Similarly, S-phase cell fractions, assessed by bromodeoxyuridine (BrdUrd) incorporation, decreased to half the initial value during the first day and developed into a gradual decrease to basal levels thereafter. Within 10 days, tumour volumes were reduced to 20% without striking changes in tissue architecture. To quantify apoptosis, we applied a method that stains DNA breaks in tissue sections and subsequently measured the stained area by automated image cytometry. This procedure was necessary, as the subtle changes could not be detected by histological examination alone. One day after the rapid decline of the S-phase fraction, a 3-fold increase in apoptotic area was observed that remained for about 3 days and then gradually decreased. This correlated with the histologically observed reduction of tumour cells. In spite of the major cell loss, regression came to a halt after about 10 days. The surviving cell fraction is discussed within the context of a stem cell hypothesis, in which tumour cells with stem cell characteristics are less susceptible to hormone-induced apoptosis than their (non-stem) daughter cells. This notion has implications for the eradication of residual tumour cells, because a diminished susceptibility might also apply to apoptosis induced by radio- or chemotherapy. Images Figure 2 Figure 3

IntroductionSentinel Lymphnode Biopsy (SLNB) is generally excepted as a minimal invasive technique to stage the axilla in clinically node negative breast cancer patients. Though the reported clinically overt axillary recurrences after negative SLNB is low (0-2,8%), these false negative results after SLNB remain a concern in the treatment of pN0(slnb) breast cancer patients. In this respect many have investigated factors that may influence the risk of developing an axillary recurrence, either to explain the unexpected low incidence or to try to identify subgroups of patients with higher risk of developing an axillary recurrence. Downside to many of these studies is the single-centre study design, mostly presenting small numbers of patients with relatively short follow-up making it difficult to extrapolate the results to the every-day practice.We conducted this multicentre cohort study to identify prognostic factors for developing axillary recurrences after negative SLNB.Patients and MethodsProspectively collected data from seven large volume hospitals in the Netherlands were analyzed. Patients underwent surgery including SLNB between January 2000 and December 2002. Pathological work-up of the sentinel node, local and systemic treatment, and follow-up were performed according to Dutch National guidelines. Statistical analysis was performed to test homogeneity between the institutes. Multivariate analysis was performed to identify prognostic factors. A p-value of 0,2mm) and underwent Axillary Lymphnode Dissection (ALND). In the remaining 1028 patients, 986 (61,7%) were SLN negative and 42 (2,6%) patients were found to have isolated tumor cells (i.e. metastases Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1006.

Introduction: Since the introduction of sentinel lymph node biopsy (SLNB) for staging breast cancer, lymphogenic micrometastases are commonly detected. The prognostic meaning of these small lymph node metastases and the consequences regarding the indication for adjuvant systemic treatment is under debate. Currently, robust data with a long time follow up are lacking.Method: Between January 2000 and December 2002 1411 patients with a cT1-2N0 breast carcinoma underwent surgery in seven hospitals in the Netherlands. Pathological examination of the sentinel node consisted of serial sectioning of SLN's and H&E and IHC staining. Based on the presence of lymph node metastases patients where divided into four groups: pN0 (n = 922), pN1micro (n = 103), pN1a (n = 285) and pN≥1b (n = 101). Median follow up was 77 months.Results: At the end of follow-up 184 (13.0%) patients had died. Breast cancer recurred in 244 (17.3%) patients, 165 of them having distant metastases (11.7%) patients. The 5- years overall survival was 93% for patients with pN0 disease, 94% for pN1micro, 88% for pN1a and 78% for pN≥1b (p < 0.001). The 5-years disease free survival was 87%, 90%, 85% and 72% (p < 0.001) respectively.Following adjustment for possible confounding characteristics and for adjuvant systemic treatment, overall survival was similar for pN0 en pN1micro patients and significantly worse for pN1a and pN≥1b (HR 1.18; 95% CI 0.58-2.39, HR 2.47; 95% CI 1.69-3.63, HR 4.36; 95% CI 2.70-7.04 respectively). Disease free survival was similar too in the pN0 and pN1micro group, and worse for pN1a and pN≥1b (HR 0.96; 95% CI 0.56-1.67 vs. HR 1.64; 95% CI 1.19-2.27, HR 2.95; CI 1.98-4.42). Distant metastases were more commonly observed in the pN1micro group than in the pN0 group (HR 1.22; 95% CI 0.60-2.49), but not significantly and far less than in the pN1a and pN≥1b group (HR 2.26; 95% CI 1.49-3.40, HR 3.49; 95% CI 2.12-5.77).Conclusion: After a relative long time of follow up disease free and overall survival for patients with micrometastasis in SLNs is comparable to patients without lymphogenic metastasis and more favourable than patients with macrometastasis. The presence of micrometastatic disease in the SLN is in itself not an indication for adjuvant systemic therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 307.

Background To evaluate the prognostic meaning of lymph node micrometastases in breast cancer patients. Methods Between January 2000 and January 2003, 1411 patients with a cT1-2N0 invasive breast carcinoma underwent surgery in 7 hospitals in the Netherlands. Sentinel lymph node biopsy was done in all patients. Based on lymph node status, patients were divided into 4 groups: pN0 (n = 922), pN1micro (n = 103), pN1a (n = 285), and pN≥1b (n = 101). Median follow-up was 6.4 years. Results At the end of follow-up, 1121 women were still alive (79.4%), 184 had died (13.0%), and 106 were lost to follow-up (7.5%). Breast cancer recurred in 244 patients: distant metastasis (n = 165), locoregional relapse (n = 83), and contralateral breast cancer (n = 44). Following adjustment for possible confounding characteristics and for adjuvant systemic treatment, overall survival (OS) remained comparable for pN0 and pN1micro and was significantly worse for pN1a and pN≥1b (hazard ratio [HR] 1.18; 95% confidence interval [95% CI] 0.58–2.39, HR 2.47; 95% CI 1.69–3.63, HR 4.36; 95% CI 2.70–7.04, respectively). Disease-free survival (DFS) was similar too in the pN0 and pN1micro group, and worse for pN1a and pN≥1b (HR 0.96; 95% CI 0.56–1.67 vs HR 1.64; 95% CI 1.19–2.27, HR 2.95; CI 1.98–4.42). The distant metastases rate also did not differ significantly between the pN0 and pN1micro group and was worse for pN1a and pN≥1b (HR 1.22; 95% CI 0.60–2.49, HR 2.26; 95% CI 1.49–3.40, HR 3.49; CI 2.12–5.77). Conclusions In breast cancer patients survival is not affected by the presence of micrometastatic lymph node involvement. Electronic supplementary material The online version of this article (doi:10.1245/s10434-010-1451-z) contains supplementary material, which is available to authorized users.