Transanal Endoscopic Microsurgery: Indications and Results

Het onderwerp van het proefschrift is transanale endoscopische microchirurgie (TEM). Het is een nieuwe, endoscopische operatie techniek via de anus voor de locale excisie van rectum tumoren. De bekende locale operatie technieken zijn weliswaar veilig, maar gaan gepaard met een hoog recidief percentage en zijn dus niet ideaal. Het alternatief is totale mesorectale excisie (TME) via een laparotomie met aanzienlijk mortaliteit en morbiditeit, waaronder een grote kans op een stoma. In het proefschrift wordt aangetoond dat TEM in vergelijking met transanale excisie, de locale operatietechniek van oudsher en het meest toegepast, ten aanzien van adenomen (goedaardige tumoren en voorstadium van kanker) een kortere operatietijd kent en veiliger is. Daarnaast is TEM veel beter in staat de adenomen in 1 stuk en met vrije snijvlakken te excideren. Daardoor is de recidiefkans na TEM klein is en veel kleiner dan na transanale excisie. Ook wordt aangetoond dat TEM geschikt is voor alle adenomen in het hele rectum. De kans dat het met TEM niet lukt is gering en neemt verder af met toegenomen ervaring van de operateur. Door voor en na TEM de defecatie en kwaliteit van leven te onderzoeken wordt aangetoond dat TEM geen negatieve invloed heeft op de defecatie en na TEM een verbetering van de kwaliteit van leven optreedt, waarschijnlijk omdat men opgelucht is dat de operatie achter de rug is zonder nadelige gevolgen. Ten aanzien rectum kanker blijkt TEM in staat met vrije snijvlakken en veilig de kanker te excideren en dus goed gebruikt te kunnen ter palliatie. In een onderzoek naar de kans op genezing voor T1 rectum kanker (het vroegste stadium) blijkt TEM veel veiliger dan TME en de overleving, zowel algeheel als kanker specifiek, niet verschillend. Na TEM komt de kanker plaatselijk wel vaker terug, waarbij de impact lijkt mee te vallen. Ook de defecatie en kwaliteit van leven na TEM en TME voor T1 rectum kanker zijn onderzocht. Het blijkt dat na TEM veel minder defecatie problemen gezien worden. De kwaliteit van leven lijkt niet verschillend. De conclusies van het proefschrift zijn dat TEM de beste techniek is voor de excisie van alle rectum adenomen, zonder nadelige gevolgen voor de defecatie en kwaliteit val leven. Voor rectum kanker is TEM geschikt als palliatie. Voor de genezing van T1 rectum kanker is TEM veiliger dan TME met minder defecatie problemen, met een identieke kans op overleving, maar met een hogere kans op locale recidivering

Multicentre study of non-surgical management of diverticulitis with abscess formation

Background: Treatment strategies for diverticulitis with abscess formation have shifted from (emergency) surgical treatment to non-surgical management (antibiotics with or without percutaneous drainage (PCD)). The aim was to assess outcomes of non-surgical treatment and to identify risk factors for adverse outcomes. Methods: Patients with a first episode of CT-diagnosed diverticular abscess (modified Hinchey Ib or II) between January 2008 and January 2015 were included retrospectively, if initially treated non-surgically. Baseline characteristics, short-term (within 30 days) and long-term treatment outcomes were recorded. Treatment failure was a composite outcome of complications (perforation, colonic obstruction and fistula formation), readmissions, persistent diverticulitis, emergency surgery, death, or need for PCD in the no-PCD group. Regression analyses were used to analyse risk factors for treatment failure, recurrences and surgery. Results: Overall, 447 patients from ten hospitals were included (Hinchey Ib 215; Hinchey II 232), with a median follow-up of 72 (i.q.r. 55–93) months. Most patients were treated without PCD (332 of 447, 74⋅3 per cent). Univariable analyses, stratified by Hinchey grade, showed no differences between no PCD and PCD in short-term treatment failure (Hinchey I: 22⋅3 versus 33 per cent, P = 0⋅359; Hinchey II: 25⋅9 versus 36 per cent, P = 0⋅149) or emergency surgery (Hinchey I: 5⋅1 versus 6 per

A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer

Background: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. Methods/Study design: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. Discussion: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. Trial registration:NCT02371304, registration date: February 2015

Incidence of Interval Colorectal Cancer After Negative Results From First-Round Fecal Immunochemical Screening Tests, by Cutoff Value and Participant Sex and Age

Background & Aims: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and the effects of different cutoff values and patient sex and age. Methods: We collected data from participants in a population-based

Perineal wound closure using gluteal turnover flap or primary closure after abdominoperineal resection for rectal cancer: study protocol of a randomised controlled multicentre trial (BIOPEX-2 study)

BACKGROUND: Abdominoperineal resection (APR) for rectal cancer is associated with high morbidity of the perineal wound, and controversy exists about the optimal closure technique. Primary perineal wound closure is still the standard of care in the Netherlands. Biological mesh closure did not improve wound healing in our previous randomised controlled trial (BIOPEX-study). It is suggested, based on meta-analysis of cohort studies, that filling of the perineal defect with well-vascularised tissue improves perineal wound healing. A gluteal turnover flap seems to be a promising method for this purpose, and with the advantage of not having a donor site scar. The aim of this study is to investigate whether a gluteal turnover flap improves the uncomplicated perineal wound healing after APR for rectal cancer. METHODS: Patients with primary or recurrent rectal cancer who are planned for APR will be considered eligible in this multicentre randomised controlled trial. Exclusion criteria are total exenteration, sacral resection above S4/S5, intersphincteric APR, biological mesh closure of the pelvic floor, collagen disorders, and severe systemic diseases. A total of 160 patients will be randomised between gluteal turnover flap (experimental arm) and primary closure (control arm). The total follow-up duration is 12 months, and outcome assessors and patients will be blinded for type of perineal wound closure. The primary outcome is the percentage of uncomplicated perineal wound healing on day 30, defined as a Southampton wound score of less than two. Secondary outcomes include time to perineal wound closure, incidence of perineal hernia, the number, duration and nature of the complications, re-interventions, quality of life and urogenital function. DISCUSSION: The uncomplicated perineal wound healing rate is expected to increase from 65 to 85% by using the gluteal turnover flap. With proven effectiveness, a quick implementation of this relatively simple surgical technique is expected to take place. TRIAL REGISTRATION: The trial was retrospectively registered at Clinicaltrials.gov NCT04004650 on July 2, 2019

Transanal minimally invasive surgery (TAMIS) versus endoscopic submucosal dissection (ESD) for resection of non-pedunculated rectal lesions (TRIASSIC study): Study protocol of a European multicenter randomised controlled trial

Background: In the recent years two innovative approaches have become available for minimally invasive en bloc resections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. Methods: Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. Discussion: This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for the en bloc resection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. Trial registration: Netherlands Trial Register, NL7083, 06 July 2018

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Progression and tumor heterogeneity analysis in early rectal cancer

Purpose: Adequate preoperative staging of large sessile rectal tumors requires identifying adenomas that already contain an invasive focus, specifically those that are growing in or beyond the submucosa. We systematically compared chromosomal instability patterns in adenoma and carcinoma fractions of the same lesion to assess specific steps in rectal tumor progression. Experimental Design: We analyzed 36 formalin-fixed, paraffin-embedded tumors. Both the adenoma and carcinoma fractions were typed with single nucleotide polymorphism arrays and compared with 21 previously described pure adenomas. Eighteen cases were included in an intratumor heterogeneity analysis. Results: Five specific "malignant" events (gain of 8q, 13q, and 20q and loss of 17p and 18q) and aberrant staining for p53 and SMAD4 were all increased in the adenoma fractions of carcinoma cases compared with pure adenomas. Paired analysis revealed that 31% of the samples had an equal amount of malignant aberrations in their adenoma and carcinoma fractions, whereas 25% had one and 33% had two or more extra malignant events in the carcinoma fraction. Analysis of three core biopsies per patient showed a large degree of intratumor heterogeneity. However, the number of malignant aberrations in the biopsy with the most aberrations per tumor correlated with the corresponding adenoma or carcinoma fraction (r = 0.807; P < 0.001). Conclusion: Five specific chromosomal aberrations, combined with immunohistochemistry for p53 and SMAD4, can predict possible progression of sessile rectal adenomas to early rectal cancer and can, after validation studies, be added to preoperative staging. Preferably, three biopsies should be taken from each tumor to address intratumor heterogeneity