Morbidity After Inguinal Lymph Node Dissections:It Is Time for a Change

Inguinal lymph node dissection (ILND) for stage 3 melanoma is accompanied by high wound complication rates. During the past decades, several changes in perioperative care have been instituted to decrease the incidence of these complications. This study aimed to evaluate the effect of these different care protocols on wound complications after ILND. A retrospective analysis of prospectively collected data was performed with 240 patients who underwent an ILND in the University Medical Center Groningen between 1989 and 2014. Four groups with different treatment protocols were analyzed: A (>= 10 days of bed rest with a Bohler Braun splint), B (10 days of bed rest without a splint), C (5 days of bed rest), and D (1 day of bed rest). The effect of early mobilization, abolishment of the Bohler Braun splint and postural restrictions, and the introduction of prophylactic antibiotics were analyzed. One or more wound complications occurred in 51.2 % of the patients including wound infection (29.8 %), seroma (21.5 %), wound necrosis (13.6 %), and hematoma (5 %). In consecutive periods, respectively 44.4, 60.3, 44.9 and 55.2 % of the patients experienced wound complications. None of the instituted changes in protocols led to a decrease in wound complications. Changes in perioperative care protocols did not affect the rate of wound complications. Perhaps a change in the surgical procedure itself can lead to the necessary reduction of wound complications after ILND

Incidence of unplanned excisions of soft tissue sarcomas in the Netherlands:A population-based study

Introduction: Timely recognition of soft tissue sarcomas (STS) remains challenging, potentially leading to unplanned excisions (also known as 'whoops procedures'). This population-based study charted the occurrence of unplanned excisions and identified associated patient, tumour, and treatment-related characteristics. Furthermore, it presents an overview of the outcomes and clinical management following an unplanned excision. Methods: From the Netherlands Cancer Registry (NCR) database, information was obtained on 2187 adult patients diagnosed with STS in 2016-2019 who underwent surgery. Tumours located in the mediastinum, heart or retroperitoneum were excluded, as well as incidental findings. Differences between patients with planned and unplanned excisions were assessed with chi-square tests and a multivariable logistic regression model. Results: Overall, unplanned excisions comprise 18.2% of all first operations for STS, with a quarter of them occurring outside a hospital. Within hospitals, the unplanned excision rate was 14.4%. Unplanned excisions were more often performed on younger patients, and tumours unsuspected of being STS prior to surgery were generally smaller ( Discussion: Potential improvement in preventing unplanned excisions may be achieved by better compliance to preoperative imaging and referral guidelines, and stimulating continuous awareness of STS among general surgeons, general practitioners and private practices. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved

Impact of cumulative complications on 1-year treatment-related healthcare costs in patients with colorectal peritoneal metastases undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

BACKGROUND: The aim of this study was to evaluate the impact of all minor and major complications on treatment-related healthcare costs in patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of colorectal peritoneal metastases (PMs). METHOD: Patients with histologically proven colorectal PMs who underwent CRS + HIPEC from March 2006 to October 2019 in a tertiary referral centre were retrospectively identified from a prospectively maintained database. Patients were divided into six subgroups according to the severity of the complications, which were scored using the comprehensive complication index (CCI) (CCI 0-9.9, CCI 10-19.9, CCI 20-29.9, CCI 30-39.9, CCI 40-49.9, and CCI 50 or higher). Treatment-related healthcare costs up to 1 year after CRS + HIPEC were obtained from the financial department. Differences in costs and survival outcomes were compared using the chi-squared test and Kruskal-Wallis H test. RESULTS: A total of 142 patients were included (CCI 0-9.9, 53 patients; CCI 10-19.9, 0 patients; CCI 20-29.9, 45 patients; CCI 30-39.9, 14 patients; CCI 40-49, 9 patients; and CCI 50 or higher, 21 patients). Median (interquartile range) treatment-related healthcare costs increased significantly and exponentially for the CCI 30-39, CCI 40-49, and CCI 50 or higher groups (€48 993 (€44 262-€84 805); €57 167 (€43 047-€67 591); and €82 219 (€55 487-€145 314) respectively) compared with those for the CCI 0-9.9 and CCI 20-29.9 groups (€33 856 (€24 433-€40 779) and €40 621 (€31 501-€58 761) respectively, P < 0.010). CONCLUSION: Treatment-related healthcare costs increase exponentially as more complications develop among patients who undergo CRS + HIPEC for the treatment of colorectal PMs. Anastomotic leakages after CRS + HIPEC lead to an increase of 295 per cent of treatment-related healthcare costs

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Tailored Beta-catenin mutational approach in extra-abdominal sporadic desmoid tumor patients without therapeutic intervention

BACKGROUND: The efficacy of the classical treatment modalities surgery and radiotherapy in the treatment of aggressive fibromatosis is presently disputed and there is a shift towards a more conservative approach. The aim of the present study is to objectify tumor growth in patients with extra-abdominal or abdominal wall aggressive fibromatosis, while adhering to a “watchful waiting” policy. Other objectives are to investigate quality of life and to identify factors associated with tumor growth, in particular the relation with the presence of a CTNNB1-gene mutation in the tumor. DESIGN AND METHODS: GRAFITI is a nationwide, multicenter, prospective registration trial. All patients with extra-abdominal or abdominal wall aggressive fibromatosis are eligible for inclusion in the study. Main exclusion criteria are: history of familiar adenomatous polyposis, severe pain, functional impairment, life/limb threating situations in case of progressive disease. Patients included in the study will be treated with a watchful waiting policy during a period of 5 years. Imaging studies with ultrasound and magnetic resonance imaging scan will be performed during follow-up to monitor possible growth: the first years every 3 months, the second year twice and the yearly. In addition patients will be asked to complete a quality of life questionnaire on specific follow-up moments. The primary endpoint is the rate of progression per year, defined by the Response Evaluation Criteria In Solid Tumors (RECIST). Secondary endpoints are quality of life and the rate of influence on tumor progression for several factors, such as CTNNB1-mutations, age and localization. DISCUSSION: This study will provide insight in tumor behavior, the effect on quality of life and clinicopathological factors predictive of tumor progression. TRIAL REGISTRATION: The GRAFITI trial is registered in the Netherlands National Trial Register (NTR), number 4714

Molecular fluorescence-guided surgery of peritoneal carcinomatosis of colorectal origin: a single-centre feasibility study

BACKGROUND: Optimum cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is essential for the curative treatment of peritoneal carcinomatosis of colorectal origin. At present, surgeons depend on visual inspection and palpation for tumour detection. Improved detection of tumour tissue using molecular fluorescence-guided surgery could not only help attain a complete cytoreduction of metastatic lesions, but might also prevent overtreatment by avoiding resection of benign lesions. METHODS: For this non-randomised, single-centre feasibility study, we enrolled patients with colorectal peritoneal metastases scheduled for cytoreductive surgery and HIPEC. 2 days before surgery, 4·5 mg of the near-infrared fluorescent tracer bevacizumab-IRDye800CW was administered intravenously. The primary objectives were to determine the safety and feasibility of molecular fluorescence-guided surgery using bevacizumab-IRDye800CW. Molecular fluorescence-guided surgery was deemed safe if no allergic or anaphylactic reactions were recorded and no serious adverse events were attributed to bevacizumab-IRDye800CW. The technique was deemed feasible if bevacizumab-IRDye800CW enabled detection of fluorescence signals intraoperatively. Secondary objectives were correlation of fluorescence with histopathology by back-table imaging of the fresh surgical specimen and semi-quantitative ex-vivo analyses of formalin-fixed paraffin embedded (FFPE) tissue on all peritoneal lesions. Additionally, VEGF-α staining and fluorescence microscopy was done. This study is registered with the Netherlands Trial Registry, number NTR4632. FINDINGS: Between July 3, 2014, and March 2, 2015, seven patients were enrolled in the study. One patient developed an abdominal sepsis 5 days postoperatively and another died from an asystole 4 days postoperatively, most probably due to a cardiovascular thromboembolic event. However, both serious adverse events were attributed to the surgical cytoreductive surgery and HIPEC procedure. No serious adverse events related to bevacizumab-IRDye800CW occurred in any of the patients. Intraoperatively, fluorescence was seen in all patients. In two patients, additional tumour tissue was detected by molecular fluorescence-guided surgery that was initially missed by the surgeons. During back-table imaging of fresh surgical specimens, a total of 80 areas were imaged, marked, and analysed. All of the 29 non-fluorescent areas were found to contain only benign tissue, whereas tumour tissue was detected in 27 of 51 fluorescent areas (53%). Ex-vivo semi-quantification of 79 FFPE peritoneal lesions showed a tumour-to-normal ratio of 6·92 (SD 2·47). INTERPRETATION: Molecular fluorescence-guided surgery using the near-infrared fluorescent tracer bevacizumab-IRDye800CW is safe and feasible. This technique might be of added value for the treatment of patients with colorectal peritoneal metastases through improved patient selection and optimisation of cytoreductive surgery. A subsequent multicentre phase 2 trial is needed to make a definitive assessment of the diagnostic accuracy and the effect on clinical decision making of molecular fluorescence-guided surgery. FUNDING: FP-7 Framework Programme BetaCure and SurgVision BV

Local treatment in metastatic GIST patients: A multicentre analysis from the Dutch GIST Registry

Background: The added value of local treatment in selected metastatic GIST patients is unclear. This study aims to provide insight into the usefulness of local treatment in metastatic GIST by use of a survey study and retrospective analyses in a clinical database. Methods: A survey study was conducted among clinical specialists to select most relevant characteristics of metastatic GIST patients considered for local treatment, defined as elective surgery or ablation. Patients were selected from the Dutch GIST Registry. A multivariate Cox-regression model for overall survival since time of diagnosis of metastatic disease was estimated with local treatment as a time-dependent variable. An additional model was estimated to assess prognostic factors since local treatment. Results: The survey's response rate was 14/16. Performance status, response to TKIs, location of active disease, number of lesions, mutation status, and time between primary diagnosis and metastases, were regarded the 6 most important characteristics. Of 457 included patients, 123 underwent local treatment, which was associated with better survival after diagnosis of metastases (HR = 0.558, 95%CI = 0.336–0.928). Progressive disease during systemic treatment (HR = 3.885, 95%CI = 1.195–12.627) and disease confined to the liver (HR = 0.269, 95%CI = 0.082–0.880) were associated with worse and better survival after local treatment, respectively. Conclusion: Local treatment is associated with better survival in selected patients with metastatic GIST. Locally treated patients with response to TKIs and disease confined to the liver have good clinical outcome. These results might be considered for tailoring treatment, but should be interpreted with care because only specific patients are provided with local treatment in this retrospective study

Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: Protocol of a multicentre, open-label, parralel-group, phase II-III, randomised, superiority study (CAIRO6)

Background: Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes. Methods: This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres. Eligible patients are adults who have a good performance status, histologically or cytologically proven resectable PM of a colorectal adenocarcinoma, no systemic colorectal metastases, no systemic therapy for colorectal cancer within six months prior to enrolment, and no previous CRS-HIPEC. Eligible patients are randomised (1:1) to perioperative systemic therapy and CRS-HIPEC (experimental arm) or upfront CRS-HIPEC alone (control arm) by using central randomisation software with minimisation stratified by a peritoneal cancer index of 0-10 or 11-20, metachronous or synchronous PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C. At the treating physician's discretion, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. The first 80 patients are enrolled in a phase II study to explore the feasibility of accrual and the feasibility, safety, and tolerance of perioperative systemic therapy. If predefined criteria of feasibility and safety are met, the study continues as a phase III study with 3-year overall survival as primary endpoint. A total of 358 patients is needed to detect the hypothesised 15% increase in 3-year overall survival (control arm 50%; experimental arm 65%). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histopathological response rates. Discussion: This is the first randomised study that prospectively compares oncological outcomes of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC alone for isolated resectable colorectal PM