Isolated Limb Perfusion with Melphalan and TNF-α in the Treatment of Extremity Sarcoma

Isolated limb perfusion (ILP) with chemotherapy alone has uniformly failed in the treatment of irresectable extremity soft tissue sarcomas. The addition of tumor necrosis factor-alpha (TNF-α) to this treatment approach contributed to a major step forward in the treatment of locally advanced extremity soft tissue sarcoma (STS). High response rates and limb salvage rates have been reported in multicenter trials, which combined ILP with TNF-α plus melphalan, which resulted in the approval of TNF-α for this indication in Europe in 1998. Subsequently a series of confirmatory single institution reports on the efficacy of the procedure have now been published. TNF-α has an early and a late effect; it enhances tumor-selective drug uptake during the perfusion and plays an essential role in the subsequent selective destruction of the tumor vasculature. These effects result in a high response rate in high-grade soft tissue sarcomas. This induction therapy thus allows for resection of tumor remnants some 3 months after ILP and thus avoidance of limb amputation. TNF-α-based ILP is a well-established treatment to avoid amputations. It represents an important example of tumor vasculatory-modulating combination therapy and should be offered in large volume tertiary referral centers

Liver Resection for Hepatic Metastases from Soft Tissue Sarcoma:A Nationwide Study

Contains fulltext : 209467pub.pdf (publisher's version ) (Open Access

Implementation of prehabilitation in colorectal cancer surgery:qualitative research on how to strengthen facilitators and overcome barriers

Purpose Prehabilitation is increasingly offered to patients with colorectal cancer (CRC) undergoing surgery as it could prevent complications and facilitate recovery. However, implementation of such a complex multidisciplinary intervention is challenging. This study aims to explore perspectives of professionals involved in prehabilitation to gain understanding of barriers or facilitators to its implementation and to identify strategies to successful operationalization of prehabilitation. Methods In this qualitative study, semi-structured interviews were performed with healthcare professionals involved in prehabilitation for patients with CRC. Prehabilitation was defined as a preoperative program with the aim of improving physical fitness and nutritional status. Parallel with data collection, open coding was applied to the transcribed interviews. The Ottawa Model of Research Use (OMRU) framework, a comprehensive interdisciplinary model guide to promote implementation of research findings into healthcare practice, was used to categorize obtained codes and structure the barriers and facilitators into relevant themes for change. Results Thirteen interviews were conducted. Important barriers were the conflicting scientific evidence on (cost-)effectiveness of prehabilitation, the current inability to offer a personalized prehabilitation program, the complex logistic organization of the program, and the unawareness of (the importance of) a prehabilitation program among healthcare professionals and patients. Relevant facilitators were availability of program coordinators, availability of physician leadership, and involving skeptical colleagues in the implementation process from the start. Conclusions Important barriers to prehabilitation implementation are mainly related to the intervention being complex, relatively unknown and only evaluated in a research setting. Therefore, physicians' leadership is needed to transform care towards more integration of personalized prehabilitation programs. Implications for cancer survivors By strengthening prehabilitation programs and evidence of their efficacy using these recommendations, it should be possible to enhance both the pre- and postoperative quality of life for colorectal cancer patients during survivorship

Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients

Background: the optimal treatment of anastomotic leak after rectal cancer resection is unclear. this worldwide cohort study aimed to provide an overview of four treatment strategies applied. Methods: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1). results: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. one-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. propensity score matching resulted in 556 patients with passive and 278 with active drainage. there was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. after active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days). Conclusion: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding

Stoma-free Survival After Rectal Cancer Resection With Anastomotic Leakage: Development and Validation of a Prediction Model in a Large International Cohort

Objective: This study aimed to develop and validate a prediction model (STOMA-score) for one-year stoma-free survival in rectal cancer (RC) patients with anastomotic leakage (AL). Background: AL after RC resection often results in a permanent stoma. Methods: This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres, and included patients who developed AL after RC surgery between 2014-2018. Clinically relevant predictors for one-year stoma-free survival were included in uni- and multivariable logistic regression models. The STOMA-score was developed and internally validated in a cohort of patients operated between 2014-2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated. Results: This study included 2499 AL patients; 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA-score: sex, age, ASA-classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal- and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction and reactivation leakage. The STOMA-score showed good discrimination and calibration (c-index 0.71, 95%CI 0.66-0.76). Conclusion: The STOMA-score consists of eighteen clinically relevant factors and estimates the individual risk for one-year stoma-free survival in patients with AL after RC surgery, which may improve patient counselling and give guidance when analyzing efficacy of different treatment strategies in future studies

Decompressing Stoma as Bridge to Elective Surgery is an Effective Strategy for Left-sided Obstructive Colon Cancer:A National, Propensity-score Matched Study

OBJECTIVE: The purpose of this population-based study was to compare decompressing stoma (DS) as bridge to surgery (BTS) with emergency resection (ER) for left-sided obstructive colon cancer (LSOCC) using propensity-score matching. SUMMARY BACKGROUND DATA: Recently, an increased use of DS as BTS for LSOCC has been observed in the Netherlands. Unfortunately, good quality comparative analyses with ER are scarce. METHODS: Patients diagnosed with nonlocally advanced LSOCC between 2009 and 2016 in 75 Dutch hospitals, who underwent DS or ER in the curative setting, were propensity-score matched in a 1:2 ratio. The primary outcome measure was 90-day mortality, and main secondary outcomes were 3-year overall survival and permanent stoma rate. RESULTS: Of 2048 eligible patients, 236 patients who underwent DS were matched with 472 patients undergoing ER. After DS, more laparoscopic resections were performed (56.8% vs 9.2%, P < 0.001) and more primary anastomoses were constructed (88.5% vs 40.7%, P < 0.001). DS resulted in significantly lower 90-day mortality compared to ER (1.7% vs 7.2%, P = 0.006), and this effect could be mainly attributed to the subgroup of patients over 70 years (3.5% vs 13.7%, P = 0.027). Patients treated with DS as BTS had better 3-year overall survival (79.4% vs 73.3%, hazard ratio 0.36, 95% confidence interval 0.20-0.65) and fewer permanent stomas (23.4% vs 42.4%, P < 0.001). CONCLUSIONS: In this nationwide propensity-score matched study, DS as a BTS for LSOCC was associated with lower 90-day mortality and better 3-year overall survival compared to ER, especially in patients over 70 years of age

20 Years Experience of TNF-Based Isolated Limb Perfusion for In-Transit Melanoma Metastases: TNF Dose Matters

Background: Approximately 5-8% of melanoma patients will develop in-transit metastases (IT-mets). Tumor necrosis factor-α (TNF) and melphalan-based isolated limb perfusion (TM-ILP) is an attractive treatment modality in melanoma patients with multiple IT-mets. This study reports on a 20 years experience and outlines the evolution and major changes since the introduction of TNF in ILP. Methods: A total of 167 TM-ILPs were performed in 148 patients, between 1991 and 2009. TM-ILPs were performed at high doses of TNF (3-4 mg) from 1991 to 2004 (n = 99) and at low doses of TNF (1-2 mg) from 2004 to 2009 (n = 68) under mild hyperthermic conditions (38°C-39.5°C.). Melphalan doses were unchanged at 10-13 mg/l (leg and arm, respectively). Characteristics for the 167 ILPs were

Isolated Hypoxic Hepatic Perfusion with Retrograde Outflow in Patients with Irresectable Liver Metastases; A New Simplified Technique in Isolated Hepatic Perfusion

Background: Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic h

Early and long-term morbidity after total laryngopharyngectomy

To determine the early and long-term morbidity of patients treated with a total laryngopharyngectomy and reconstruction using a jejunum interposition or gastric pull-up procedure. It is a retrospective study; and it is conducted in tertiairy referral center. Sixty-three patients were included in whom 70 reconstructions were performed (51 jejunum interpositions and 19 gastric pull-up procedures) between 1990 and 2007. The studied parameters were success rate of the reconstruction, early and long-term complication rate, and functional outcome including quality of life. Subjective quality of life analysis was determined by two questionnaires: the EORTC Quality of Life Questionnaire (QLQ)-C30 Dutch version 3.0, and the EORTC-Head and Neck (H & N 35). The success rates were 84 and 74%, respectively. The procedures were associated with a high complication rate (63% after jejunum interposition and 89% after gastric pull-up), and a lengthy rehabilitation. Surviving patients were found to have a good long-term quality of life. Complete oral intake was achieved in 97%, and speech rehabilitation in 95%. These procedures are associated with significant morbidity, high complication rates, lengthy rehabilitation, but a good long-term quality of life

Insurance Firms in Process of Industrialization

Background: Primary perineal wound closure after conventional abdominoperineal resection (cAPR) for rectal cancer has been the standard of care for many years. Since the introduction of neo-adjuvant radiotherapy and the extralevator APR (eAPR), oncological outcome has been improved, but at the cost of increased rates of perineal wound healing problems and perineal hernia. This has progressively increased the use of biological meshes, although not supported by sufficient evidence. The aim of this study is to determine the effectiveness of pelvic floor reconstruction using a biological mesh after standardized eAPR with neo-adjuvant (chemo) radiotherapy compared to primary perineal wound closure. Methods/Design: In this multicentre randomized controlled trial, patients with a clinical diagnosis of primary rectal cancer who are scheduled for eAPR after neo-adjuvant (chemo) radiotherapy will be considered eligible. Exclusion criteria are prior radiotherapy, sacral resection above S4/S5, allergy to pig products or polysorbate, collagen disorders, and severe systemic diseases affecting wound healing, except for diabetes. After informed consent, 104 patients will be randomized between standard care using primary wound closure of the perineum and the experimental arm consisting of suturing a biological mesh derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar to the control arm. Patients will be followed for one year after the intervention and outcome assessors and patients will be blinded for the study treatment. The primary endpoint is the percentage of uncomplicated perineal wound healing, defined as a Southampton wound score of less than II on day 30. Secondary endpoints are hospital stay, incidence of perineal hernia, quality of life, and costs. Discussion: The BIOPEX-study is the first randomized controlled multicentre study to determine the additive value of using a biological mesh for perineal wound closure after eAPR with neo-adjuvant radiotherapy compared to primary perineal wound closure with regard to perineal wound healing and the occurrence of perineal hernia