Post-operative Day 1 Serum Transaminase Levels in Relation to Morbidity After Liver Resection.

BACKGROUND: Post-operative serum transaminases have been proposed as possible early predictors of morbidity after liver resection. This study aimed to verify the clinical value of post-operative serum transaminases. METHODS: Clinical data from 2001 to 2016 in a single non-academic referral HPB center were collected from a prospectively held database. Post-operative day 1 serum aspartate transaminase (AST) and alanine transaminase (ALT) were tested for their relationship with post-operative major morbidity, defined by a Clavien-Dindo score 3 or higher, and mortality. RESULTS: For this analysis, 371 patients were included, including 149 (40%) undergoing major liver resections. In total, 17% of the patients developed major morbidity. Stepwise logistic regression demonstrated that AST, and not ALT, is an independent predictor for major morbidity (p = 0.017). The probability of major morbidity significantly increased with increasing AST values. A threshold value of 242 U/L was found to be predictive for one or more major complications. CONCLUSIONS: In this study, post-operative serum AST on day 1 was a predictive factor for major morbidity after liver resection. For patients with low AST value, early discharge could be considered. However, because of the substantial inter-individual variability of AST values, more studies are needed to translate these results into clinical practice.

Avoiding Unnecessary Major Rectal Cancer Surgery by Implementing Structural Restaging and a Watch-and-Wait Strategy After Neoadjuvant Radiochemotherapy.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is found in 15-20% of patients with locally advanced rectal cancer. A watch-and-wait (W&W) strategy has been introduced as an alternative strategy to avoid surgery for selected patients with a clinical complete response at multidisciplinary response evaluation. The primary aim of this study was to evaluate the efficacy of the multidisciplinary response evaluation by comparing the proportion of patients with pCR since the introduction of the structural response evaluation with the period before response evaluation. METHODS: This retrospective cohort study enrolled patients with locally advanced rectal cancer who underwent nCRT between January 2009 and May 2018, categorizing them into cohort A (period 2009-2015) and cohort B (period 2015-2018). The patients in cohort B underwent structural multidisciplinary response evaluation with the option of the W&W strategy. Proportion of pCR (ypT0N0), time-to-event (pCR) analysis, and stoma-free survival were evaluated in both cohorts. RESULTS: Of the 259 patients in the study, 21 (18.4%) in cohort A and in 8 (8.7%) in cohort B had pCR (p = 0.043). Time-to-event analysis demonstrated a significant pCR decline in cohort B (p < 0.001). The stoma-free patient rate was 24% higher in cohort B (p < 0.001). CONCLUSION: Multidisciplinary clinical response evaluation after nCRT for locally advanced rectal cancer led to a significant decrease in unnecessary surgery for the patients with a complete response.

Possible Preventable Causes of Unplanned Readmission After Elective Liver Resection, Results from a Non-academic Referral HPB Center.

INTRODUCTION: Unplanned readmission is a common event after liver resection, and it is a burden for both patients and healthcare policy makers. This study evaluates the incidence of and reasons for unplanned readmission after liver resection, in order to identify possible preventable causes. METHODS: In this single-center cohort study, data from patients who underwent liver resection for both malignant and benign indications from 2001 to 2016 at our institute were collected from a database with prospective data. Readmissions were analyzed for their reasons and risk factors. Patients with general complaints with no specific complications were categorized as failure to thrive. RESULTS: In 406 patients, the readmission rate was 11.6%. Most patients were readmitted because of failure to thrive (35%), deep and superficial surgical site infection (28%), or cardiopulmonary complications (15%). A multivariate analysis revealed that unplanned readmission was associated with the occurrence of complications during index admission-with an odds ratio of 4.69 (CI 2.41-9.12, p < 0.001). CONCLUSION: Readmission occurs in more than 1 in 10 patients after liver resection, and it is associated with a complicated course during index admission. One-third of readmissions occur because of failure to thrive and might be preventable. Future research in strategies to reduce readmission rates should focus on both the prevention of complications during index admission and programs at the interface between primary and secondary care.

Effectiveness of endosponge therapy for the management of presacral abscesses following rectal surgery.

BACKGROUND: Anastomotic leak after rectal surgery is reported in 9% (range 3-28%) of patients. The aim of our study was to evaluate the effectiveness of endosponge therapy for anastomotic. Endpoints were the rate of restored continuity and the functional bowel outcome after anastomotic leakage. METHODS: This was a multicenter retrospective observational cohort study. All patients with symptomatic anastomotic leakage after rectal surgery who had endosponge therapy between January 2012 and August 2017 were included. Functional bowel outcome was measured using the low anterior resection syndrome (LARS) score system. RESULTS: Twenty patients were included. Eighteen patients had low anterior resection (90%) for rectal cancer. A diverting ileostomy was performed at primary surgical intervention in 14 patients (70%). Fourteen patients (70%) were treated with neoadjuvant (chemo-)radiotherapy. The median time between primary surgical intervention and first endosponge placement was 21 (5-537) days. The median number of endosponge changes was 9 (2-28). The success rate of the endosponge treatment was 88% and the restored gastrointestinal continuity rate was 73%. A chronic sinus occurred in three patients (15%). All patients developed LARS, of which 77% reported major LARS. CONCLUSIONS: Endosponge therapy is an effective treatment for the closure of presacral cavities with high success rate and leading to restored gastrointestinal continuity in 73%. However, despite endosponge therapy many patients develop major LARS.

Patients' experiences with pre-test genetic counseling provided by breast cancer healthcare professionals: Results from a large prospective multicenter study.

BACKGROUND: Pre-test genetic counseling of patients with breast cancer is increasingly being offered by non-genetic healthcare professionals. We aimed to evaluate the experiences of patients with breast cancer receiving pre-test genetic counseling from a non-genetic healthcare professional (i.e., surgeon or nurse). METHODS: Patients who were diagnosed with breast cancer and received pre-test counseling from their surgeon or nurse (mainstream group), and patients who received pre-test counseling from a clinical geneticist (usual care group) were invited to participate in our multicenter study. Between September 2019 and December 2021, patients received a questionnaire after pre-test counseling (T0) and four weeks after receiving their test results (T1) to evaluate psychosocial outcomes, knowledge, discussed topics and satisfaction. RESULTS: We included 191 patients in our mainstream and 183 patients in our usual care group and received, respectively 159 and 145 follow-up questionnaires. Levels of distress and decisional regret were comparable in both groups. Decisional conflict was higher in our mainstream group (p = 0.01), but only 7% had clinically relevant decisional conflict (vs 2% in usual care group). The possible implications of a genetic test on (secondary) breast or ovarian cancer risks were less frequently discussed in our mainstream group (p = 0.03 and p = 0.000, respectively). In both groups knowledge about genetics was comparable, satisfaction was high and the majority of patients in both groups preferred to give both verbal and written consent for genetic testing. CONCLUSION: Mainstreamed genetic care provides sufficient information for the majority of breast cancer patients to decide about genetic testing with minimal distress.

Risk of breast implant removal after one- versus two-stage breast reconstructive surgery.

BACKGROUND: To date, both one- and two-stage techniques are used in immediate 'implant-based breast reconstruction' (IBBR) after mastectomy. Because it is still unknown what technique offers the best clinical outcomes, a multicenter retrospective study was conducted to compare both breast reconstruction techniques. METHODS: All patients, who underwent a mastectomy followed by immediate one- or two-stage IBBR during 2010 - 2016 were included. Our primary outcome measure was explantation of the 'tissue expander' (TE) and/ or implants within 60 days after breast reconstruction. Secondary outcomes were overall complication rate and secondary corrections. FINDINGS: Among a total of 383 women, TE/ implant explantation rate was higher in one-stage (19.9%) than in two-stage (11.3%) treated patients (p = 0.082). Overall complication rate (35.7% and 19.9% respectively, p = 0.008) and secondary corrections (29.8% and 20.3% respectively, p = 0.156) were also higher in one-stage compared to two-stage IBBR respectively. However, explantation (OR = 1.55; 95%CI = 0.67-3.58, p = 0.301) and complication (OR = 1.85; 95%CI = 0.92-3.37, p = 0.084) rates were comparable in one- and two-stage IBBR in our stratified multivariate logistic regression analyses, when controlling for history of smoking, nipple-sparing mastectomy, neoadjuvant radiation therapy, and removed breast tissue weight. A remarkable outcome in this study is that women treated with prophylactic surgery were more likely to have an explantation of the TE/ implant after a one-stage IBBR (OR = 4.49; 95%CI = 1.10-18.3, p = 0.037) than two-stage IBBR. In contrast, no association between type of IBBR and risk of TE/implants removal was found among women with a therapeutic mastectomy (OR = 0.82; 95%CI = 0.24-2.79, p =  = 0.74). CONCLUSION: One- and two-stage IBBR showed a comparable explantation and complication rate in our retrospective study. In one-stage IBBR more secondary corrections were detected. In addition, women who have to decide on a prophylactic mastectomy should be aware of a significantly higher risk of explantation of their implant after one-stage IBBR.

Colonic work-up after incomplete colonoscopy: significant new findings during follow-up.

BACKGROUND AND STUDY AIMS: Cecal intubation is not achieved in 2 - 23 % of colonoscopies. The efforts made by physicians to visualize the remaining colon and the number of missed significant lesions are unknown. This study evaluates 1) the reasons for incomplete colonoscopy, 2) the rates of complete colonic evaluation after incomplete colonoscopy, and 3) the number of (pre-) malignant lesions missed by incomplete colonoscopy. PATIENTS AND METHODS: In this population-based cohort study index colonoscopies were performed between September and December 2005. Prospectively collected data from consecutive patients with an incomplete colonoscopy were analyzed. For up to 18 months after the index colonoscopy, any further examinations performed in these patients were identified retrospectively. These secondary examinations included: repeat colonoscopy, computed tomography (CT) colonography, barium enema, abdominal CT scan, and surgery involving the colorectum. RESULTS: Of 5278 colonoscopies, 511 were incomplete (9.7 %). The most frequent causes of incomplete colonoscopy were looping of the scope (20.4 %), patient discomfort (15.3 %), and obstructing tumor (13.9 %). Secondary examination was performed in 278 patients (54.4 %) after incomplete colonoscopy. Patients undergoing surveillance after colorectal cancer (CRC) (78.9 %) and those with anemia (73.1 %) most frequently received a secondary examination. Incomplete colonoscopies due to stenosis (78.9 %), severe inflammation (77.8 %) or an obstructing tumor (74.6 %) were most frequently followed by a secondary examination. In all of the follow-up examinations, CRC was diagnosed in 18 patients (3.5 %) and advanced adenoma in four patients (0.8 %). CONCLUSIONS: In 4.3 % of the patients, advanced neoplasia was missed by incomplete colonoscopy. Our data therefore suggest that additional imaging is obligatory to visualize the remaining colon adequately.

Feasibility of volatile organic compound in breath analysis in the follow-up of colorectal cancer: A pilot study.

BACKGROUND: Colorectal carcinoma (CRC) has a worldwide incidence of 1.4 million patients and a large share in cancer-related mortality. After curative treatment, the risk of recurrence is 30-65%. Early detection may result in curative treatment. However, current follow-up (FU) examinations have low sensitivity ranging from 49 to 85% and are associated with high costs. Therefore, the search for a new diagnostic tool is justified. Analysis of volatile organic compound in exhaled air through an electronic nose (eNose) is a promising new patient-friendly diagnostic tool. We studied whether the eNose under investigation, the Aeonose™, is able to detect local recurrence or metastases of CRC. METHODS: In this cross-sectional study we included 62 patients, all of whom underwent curative treatment for CRC in the past 5 years. Thirty-six of them had no metastases and 26 had extraluminal local recurrence or metastases of CRC, detected during FU. Breath testing was performed and machine learning was used to predict extraluminal recurrences or metastases, and based on the receiver operating characteristics (ROC)-curve both sensitivity and specificity were calculated. RESULTS: The eNose identified extra luminal local recurrences or metastases of CRC with a sensitivity and specificity of 0.88 (CI 0.69-0.97) and 0.75 (CI 0.57-0.87), respectively, with an overall accuracy of 0.81. DISCUSSION: This eNose may be a promising tool in detecting extraluminal local recurrences or metastases in the FU of curatively treated CRC. However, a well-designed prospective study is warranted to show its accuracy and predictive value before it can be used in clinical practice.

Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients.

BACKGROUND: The global push for the use of hydroxychloroquine (HCQ) and chloroquine (CQ) against COVID-19 has resulted in an ongoing discussion about the effectivity and toxicity of these drugs. Recent studies report no effect of (H)CQ on 28-day mortality. We investigated the effect of HCQ and CQ in hospitalized patients on the non-ICU COVID-ward. METHODS: A nationwide, observational cohort study was performed in The Netherlands. Hospitals were given the opportunity to decide independently on the use of three different COVID-19 treatment strategies: HCQ, CQ, or no treatment. We compared the outcomes between these groups. The primary outcomes were 1) death on the COVID-19 ward, and 2) transfer to the intensive care unit (ICU). RESULTS: The analysis included 1064 patients from 14 hospitals: 566 patients received treatment with either HCQ (n = 189) or CQ (n = 377), and 498 patients received no treatment. In a multivariate propensity-matched weighted competing regression analysis, there was no significant effect of (H)CQ on mortality on the COVID ward. However, HCQ was associated with a significantly decreased risk of transfer to the ICU (hazard ratio (HR) = 0.47, 95% CI = 0.27-0.82, p = 0.008) when compared with controls. This effect was not found in the CQ group (HR = 0.80, 95% CI = 0.55-1.15, p = 0.207), and remained significant after competing risk analysis. CONCLUSION: The results of this observational study demonstrate a lack of effect of (H)CQ on non-ICU mortality. However, we show that the use of HCQ - but not CQ - is associated with a 53% reduction in risk of transfer of COVID-19 patients from the regular ward to the ICU. Recent prospective studies have reported on 28-day, all-cause mortality only; therefore, additional prospective data on the early effects of HCQ in preventing transfer to the ICU are still needed.

Relationship between clinical outcomes and Dutch frailty score among elderly patients who underwent surgery for hip fracture.

BACKGROUND: Frailty is a geriatric condition that is associated with an increased risk of mortality and functional decline. To date, mainly the Groningen Frailty Indicator (GFI) and Hospital Safety Management (VeiligheidsManagementSysteem [VMS]) frailty score are used to determine frailty in several hospitals in the Netherlands. However, it is yet unknown, which method has the best predictive value on clinical outcomes. OBJECTIVE: The aim of this study was to investigate the predictive value of GFI and VMS on clinical outcomes among patients who underwent hip fracture surgery. DESIGN: This is a prospective observational cohort study. METHODS: We selected all patients aged 70 years or higher, who underwent hip fracture surgery in our general hospital, between November 2014 and November 2015. Among all patients, VMS, GFI and Barthel-20 index (BI) were assessed. McNemar's paired test and Cohen's κ were used to examine the difference and the level of agreement between the two scoring methods. Kaplan-Meier and multivariable regression analyses were performed to determine overall survival and mortality, respectively, 3 years and 30 days after surgery. RESULTS: A total of 280 patients were included in the study. The median follow-up was 25 months. No systematic difference was found between the two methods (P=0.237), while a fair level of agreement could be measured (κ=0.363 [95% CI =0.23-50]). VMS showed a statistically significant difference in overall survival as compared to nonfrail patients (57 vs 80%, respectively [P logrank <0.001] with an HR of 3.5 [95% CI =2.1-5.7; P<0.001]). Classification according to GFI yielded a lower but still significant HR 2.3 (95% CI =1.2-4.1; P=0.008). CONCLUSION: VMS can be used in classifying frailty, whereby VMS frailty score is associated with clinical outcomes as overall survival mortality in older patients with hip fracture and who underwent surgery.

Cancer risks in BRCA2 families: estimates for sites other than breast and ovary.

BACKGROUND: In BRCA2 mutation carriers, increased risks have been reported for several cancer sites besides breast and ovary. As most of the families included in earlier reports were selected on the basis of multiple breast/ovarian cancer cases, it is possible that risk estimates may differ in mutation carriers with a less striking family history. METHODS: In the Netherlands, 139 BRCA2 families with 66 different pathogenic mutations were included in a nationwide study. To avoid testing bias, we chose not to estimate risk in typed carriers, but rather in male and female family members with a 50% prior probability of being a carrier (n = 1811). The relative risk (RR) for each cancer site with the exception of breast and ovarian cancer was determined by comparing observed numbers with those expected, based on Dutch cancer incidence rates. RESULTS: We observed an excess risk for four cancer sites: pancreas (RR 5.9; 95% confidence interval (CI) 3.2 to 10.0), prostate (2.5; 1.6 to 3.8), bone (14.4; 2.9 to 42.1) and pharynx (7.3; 2.0 to 18.6). A small increase was observed for cancer of the digestive tract (1.5; 1.1 to 1.9). Histological verification was available for 46% of the tumours. Nearly all increased risks reached statistical significance for men only. Cancer risks tended to be higher for people before the age of 65 years. Moreover, families with mutations outside the previously defined ovarian cancer cluster region tended to have a higher cancer risk. CONCLUSIONS: We found that BRCA2 carriers are at increased risk for cancers of the prostate and pancreas, and possibly bone and pharynx. Larger databases with extended follow up are needed to provide insight into mutation specific risks of selected carriers in BRCA2 families.

A Randomised Controlled Trial of Consent Procedures for the Use of Residual Tissues for Medical Research: Preferences of and Implications for Patients, Research and Clinical Practice.

BACKGROUND: Despite much debate, there is little evidence on consequences of consent procedures for residual tissue use. Here, we investigated these consequences for the availability of residual tissue for medical research, clinical practice, and patient informedness. METHODS: We conducted a randomised clinical trial with three arms in six hospitals. Participants, patients from whom tissue had been removed for diagnosis or treatment, were randomised to one of three arms: informed consent, an opt-out procedure with active information provision (opt-out plus), and an opt-out procedure without active information provision. Participants received a questionnaire six weeks post-intervention; a subsample of respondents was interviewed. Health care providers completed a pre- and post-intervention questionnaire. We assessed percentage of residual tissue samples available for medical research, and patient and health care provider satisfaction and preference. Health care providers and outcome assessors could not be blinded. RESULTS: We randomised 1,319 patients, 440 in the informed consent, 434 in the opt-out plus, and 445 in the opt-out arm; respectively 60.7%, 100%, and 99.8% of patients' tissue samples could be used for medical research. Of the questionnaire respondents (N = 224, 207, and 214 in the informed consent, opt-out plus, and opt-out arms), 71%, 69%, and 31%, respectively, indicated being (very) well informed. By questionnaire, the majority (53%) indicated a preference for informed consent, whereas by interview, most indicated a preference for opt-out plus (37%). Health care providers (N = 35) were more likely to be (very) satisfied with opt-out plus than with informed consent (p = 0.002) or opt-out (p = 0.039); the majority (66%) preferred opt-out plus. CONCLUSION: We conclude that opt-out with information (opt-out plus) is the best choice to balance the consequences for medical research, patients, and clinical practice, and is therefore the most optimal consent procedure for residual tissue use in Dutch hospitals. TRIAL REGISTRATION: Dutch Trial Register NTR2982.

Response to radiation therapy and prognosis in breast cancer patients with BRCA1 and BRCA2 mutations.

BACKGROUND AND PURPOSE: The purpose of this study is to evaluate overall survival in BRCA1 or BRCA2 breast cancer patients, describe presenting stage, review histologic findings and evaluate response to radiotherapy. MATERIALS AND METHODS: A retrospective study was performed evaluating breast cancer patients with known mutations of BRCA1 or BRCA2. Patients from 12 different pedigrees were cross-referenced with the Utah Cancer Registry (UCR), histologic findings were verified and radiotherapy records were reviewed for acute response to treatment. Actuarial survival calculations were performed and patients were matched for age, date of diagnosis and tumor size. RESULTS: Thirty breast cancer patients with BRCA1 mutations were found to have 34 breast cancers (four had bilateral metachronous lesions) and 20 breast cancer patients with BRCA2 mutations were found to have 22 breast cancers (two had bilateral metachronous disease). The median age at diagnosis was 49 years (range 21-77 years) and 42 years (range 23-83 years), respectively, for BRCA1 and BRCA2 patients. Unusual histologic types of breast cancers were represented with 7% (4/56) medullary and 5% (3/56) lobular carcinomas. Complete staging was possible for 63% (35/56) of cancers. Stages I, II, III and IV represented 26, 63, 6 and 6% of cancers, respectively. The most severe radiation reaction was moist desquamation which was self-limiting and developed in 29% (6/21) of irradiated patients. The mean follow-up was 9.8 and 7.5 years for BRCA1 and BRCA2 cancers, respectively. Kaplan-Meier survival analysis demonstrated 5-year survival values of 75% for BRCA1 patients, 73% for BRCA2 patients, 70% for matched controls and 69% for UCR controls. No statistically significant differences were evident between the groups at 5 or 10 years. CONCLUSIONS: Despite their younger age at presentation, breast cancer patients harboring BRCAI or BRCA2 mutations present at a similar stage, display a normal acute reaction to radiotherapy and have a similar prognosis when compared with sporadic breast cancer patients.

Accuracy of tympanic and infrared skin thermometers in children.

BACKGROUND: Rectal measurement is considered a gold standard in many healthcare systems for body temperature measurement in children. Although this method has several disadvantages, an ideal alternative thermometer has not yet been introduced. However tympanic and infrared skin thermometers are potential alternatives. METHODS: A prospective cohort study was performed including 100 children between 0 and 18 years of age admitted to the general paediatric ward of Spaarne Hospital in The Netherlands between January and March 2009. The objectives of this study are to evaluate the accuracy of tympanic and two types of infrared skin thermometers (Beurer and Thermofocus) compared to rectal measurement and furthermore to evaluate the influence of different variables on temperature measurements. RESULTS: Compared to rectal measurement (37.56°C), the mean temperatures of the tympanic (37.29°C), Beurer (36.79°C) and Thermofocus (37.30°C) thermometers differed significantly (p<0.001). Mean and SD of differences between rectal temperature and temperature measured with these alternative devices varied significantly (p<0.001). Sensitivity, specificity, positive and negative predictive values for detecting rectal fever measured with the tympanic, Beurer and Thermofocus thermometers are unacceptable, especially for the Beurer thermometer. This difference in temperature between rectal and the alternative thermometers remained after stratification on gender, age, skin colour and otoscopic abnormalities. CONCLUSIONS: In this study the authors demonstrated that the tympanic, Beurer and Thermofocus thermometers cannot reliably predict rectal temperature. Therefore the authors do not advise replacement of rectal measurement as the gold standard for detecting fever in children by one of these devices. When rectal measurement is not used, the infrared skin thermometers appear to perform less well than tympanic measurements.

Derivation of clones from the choroideremia locus by preparative field inversion gel electrophoresis.

By making use of preparative field inversion gel electrophoresis, we have constructed a lambda ZAP library that is highly enriched for sequences from the choroideremia locus. In vivo excision of pBluescript SK(-) constructs from lambda ZAP obviates the subcloning of DNA inserts and allows for rapid processing of several hundred recombinants. From a 625 kb Sfil fragment we isolated 7 clones that were physically mapped using microdeletions associated with the disease. One of these clones is located within, or just telomeric to, the choroideremia gene and detects two restriction fragment length polymorphisms (RFLPs). Another clone detects a RFLP which maps centromeric to the disease locus. Together these probes should improve the reliability of linkage analysis in choroideremia families and should pave the way for the isolation of the choroideremia gene.