Long-term outcomes after close rectal dissection and total mesorectal excision in ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: During ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC), rectal dissection can be performed via close rectal dissection (CRD) or in a total mesorectal excision plane (TME). Although CRD should protect autonomic nerve function, this technique may be more challenging than TME. The aim of this study was to compare long-term outcomes of patients undergoing CRD and TME. METHODS: This single-centre retrospective cohort study included consecutive patients who underwent IPAA surgery for UC between January 2002 and October 2017. Primary outcomes were chronic pouch failure (PF) among patients who underwent CRD and TME and the association between CRD and developing chronic PF. Chronic PF was defined as a pouch-related complication occurring ≥ 3 months after primary IPAA surgery requiring redo pouch surgery, pouch excision or permanent defunctioning ileostomy. Secondary outcomes were risk factors and causes for chronic PF. Pouch function and quality of life were assessed via the Pouch dysfunction score and Cleveland global quality of life score. RESULTS: Out of 289 patients (155 males, median age 37 years [interquartile range 26.5-45.5 years]), 128 underwent CRD. There was a shorter median postoperative follow-up for CRD patients than for TME patients (3.7 vs 10.9 years, p < 0.01). Chronic PF occurred in 6 (4.7%) CRD patients and 20 (12.4%) TME patients. The failure-free pouch survival rate 3 years after IPAA surgery was comparable among CRD and TME patients (96.1% vs. 93.5%, p = 0.5). CRD was a no predictor for developing chronic PF on univariate analyses (HR 0.7 CI-95 0.3-2.0, p = 0.54). A lower proportion of CRD patients developed chronic PF due to a septic cause (1% vs 6%, p = 0.03). CONCLUSIONS: Although differences in chronic PF among CRD and TME patients were not observed, a trend toward TME patients developing chronic pelvic sepsis was detected. Surgeons may consider performing CRD during IPAA surgery for UC.

[Bone marrow fibrosis in primary myelofibrosis in relation to myelodysplasia- and age-related mutations of hematopoietic cells]. / Knochenmarkfibrose bei primärer Myelofibrose in Abhängigkeit von myelodysplasie- und altersassoziierten Mutationen der Hämatopoese.

Besides histopathological findings, there are no indicators of increased risk for fibrotic progression in myeloproliferative neoplasms (MPNs). Age-related clonal hematopoiesis (ARCH) or clonal hematopoiesis of indetermined potential (CHIP) are frequent findings in the elderly and combinations with MPN driver mutations (JAK2, MPL, and CALR) have been described. To determine the impact of ARCH/CHIP-related mutations for the development of fibrosis in primary myelofibrosis (PMF), the mutational status of cases with fibrotic progression from grade 0 to grade 2/3 (n = 77) as evidenced by follow-up bone marrow biopsies (median 6.2 years) was compared to prefibrotic PMF samples without the development of fibrosis (n = 27; median follow-up 7.3 years). Frequent ARCH/CHIP-associated mutations (TET2, ASXL1, DNMT3A) demonstrable at presentation were not connected with fibrotic progression. However, mutations that are rarely found in ARCH/CHIP (SRSF2, U2AF1, SF3B1, IDH1/2, and EZH2) were present in 24.7% of cases with later development of fibrosis and not detectable in cases staying free from fibrosis (P = 0.0028). Determination of tumor mutational burden (TMB) in a subgroup of cases (n = 32) did not show significant differences (7.68 mutations/MB vs. 6.85 mutations/MB). We conclude that mutations rarely found in ARCH/CHIP provide an independent risk factor for rapid fibrotic progression (median 2.0 years) when already manifest at first presentation.

[Liquid biopsy in tumor diagnostics : Applications, perspectives, and limitations of the "cancer liquidome"]. / Liquid Biopsy in der Tumordiagnostik : Anwendungen, Perspektiven und Limitationen des Cancer Liquidome.

The detection of tumor-specific genetic alterations in body fluids as an addition to or even replacement for established tissue-based tumor diagnostics is currently a hot topic in academic research and industry. Progress in methods for nucleic acid analyses together with promising results from clinical studies have raised great expectations for cancer screening, diagnosis, prognosis, and therapy monitoring by means of a minimally invasive blood draw. Individual focused assays have already been introduced into routine diagnostics and represent a valuable option in cases where no tissue samples are available. However, before the use of liquid biopsy outside of clinical studies is enforced and more complex markers (like tumor mutational burden) are analyzed, several practical challenges and principal problems have to be addressed. This review focusses on the detection of free-circulating nucleic acids in blood plasma and critically discusses established and future applications as well as challenges and limitations of this new method.

External validation of a prognostic model of preoperative risk factors for failure of restorative proctocolectomy.

AIM: The Cleveland Clinic has proposed a prognostic model of preoperative risk factors for failure of restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis. The model incorporates four predictive variables: completion proctectomy, handsewn anastomosis, diabetes mellitus and Crohn's disease. The aim of the present study was to perform an external validation of this model in a new cohort of patients who had RPC. METHOD: Validation was performed in a multicentre cohort of 747 consecutive patients who had an RPC between 1990 and 2015 in three tertiary-care facilities, using a Kaplan-Meier survival analysis and Cox regression analysis. The performance of the model was expressed using the Harrell concordance error rate. The primary outcome measure was pouch survival with maintenance of anal function. RESULTS: During the study period, 45 (6.0%) patients experienced failure at a median interval of 31 months (interquartile range 9-82 months) from the original RPC. Multivariable analysis showed handsewn anastomosis to be the only significant independent predictor. The Harrell concordance error rate was 0.42, indicating poor performance. Anastomotic leakage and Crohn's disease of the pouch were strong postoperative predictors for pouch failure and showed a significant difference in pouch survival after 10 years (P < 0.001). CONCLUSION: The poor performance of the Cleveland Clinic prognostic model makes it unsuitable for daily clinical practice. Handsewn anastomosis was associated with pouch failure in our cohort with relatively few events. A prediction model for anastomotic leakage or Crohn's disease of the pouch may be a better solution since these variables are strongly associated with pouch failure.

Impact of obesity on disability, function, and physical activity: data from the Osteoarthritis Initiative.

OBJECTIVES: Older adults with obesity are at risk for osteoarthritis (OA) and are predisposed to functional decline and disability. We examined the association between obesity and disability, physical activity, and quality of life at 6 years. METHOD: Using data from the longitudinal Osteoarthritis Initiative (OAI), we analysed older adults (age ≥ 60 years) with a body mass index (BMI) at baseline ≥ 18.5 kg/m(2) (n = 2378) using standard BMI categories. Outcomes were assessed at the 6-year follow-up and included: the Late-Life Function and Disability Index (LLDI), the 12-item Short Form Health Survey (SF-12), and the Physical Activity Scale for the Elderly (PASE). Linear regression predicted outcomes based on BMI category, adjusting for age, sex, race, education, smoking, cohort status, radiographic knee OA, co-morbidity scores, and baseline scores when available. RESULTS: Follow-up data were available for 1727 (71.9%) participants (mean age 67.9 ± 5.3 years; 61.6% female). At baseline, obese subjects compared to overweight and normal were on a greater number of medications (4.28 vs. 3.63 vs. 3.32), had lower gait speeds (1.22 vs. 1.32 vs. 1.36 m/s), higher Charlson scores (0.59 vs. 0.37 vs. 0.30), and higher Western Ontario and McMaster University OA Index (WOMAC) scores (right: 14.8 vs. 10.3 vs. 7.5; left: 14.4 vs. 9.9 vs. 7.5). SF-12 scores at 6 years were lower in obese patients than in overweight or normal [99.5 (95% CI 98.7-100.4) vs. 101.1 (95% CI 100.4-101.8) vs. 102.8 (95% CI 101.8-103.8)], as were PASE scores [115.1 (95% CI 110.3-119.8) vs. 126.2 (95% CI 122.2-130.2) vs. 131.4 (95% CI 125.8-137.0)]. The LLDI limitation component demonstrated differences in obese compared to overweight or normal [78.6 (95% CI 77.4-79.9) vs. 81.2 (95% CI 80.2-82.3) vs. 82.5 (95% CI 81.1-84.0)]. CONCLUSIONS: Obesity was associated with worse physical activity scores, lower quality of life, and higher risk of 6-year disability.

Short-term morbidity and quality of life from a randomized clinical trial of close rectal dissection and total mesorectal excision in ileal pouch-anal anastomosis.

BACKGROUND: Posterior rectal dissection during ileal pouch-anal anastomosis (IPAA) can be performed in the total mesorectal excision (TME) or close rectal dissection (CRD) plane. The aim of this study was to compare morbidity and quality of life (QoL) in patients having TME or CRD during proctectomy followed by IPAA for benign disease. METHODS: In this randomized clinical trial, patients undergoing IPAA were allocated to TME or CRD. Thirty-day morbidity was determined and QoL assessed using Short Form 36, GIQLI (GastroIntestinal Quality of Life Index) and COREFO (COloREctal Functional Outcome) questionnaires. The primary outcome (pouch compliance) of the trial is to be reported separately. RESULTS: Fifty-nine patients were included, 28 in the CRD and 31 in the TME group. Baseline data were similar, except for more previous abdominal surgery in the TME group. Operating time was longer for patients having CRD (195 min versus 166 min for TME; P = 0·008). More patients in the TME group had a primary defunctioning ileostomy (7 of 31 versus 1 of 28 for CRD; P = 0·055). Severe complications occurred more frequently in the TME group (10 of 31 versus 2 of 28 for CRD). QoL was better in the CRD group for several subscales of the questionnaires measured at 1, 3 and 6 months after surgery. At 12 months, QoL was similar in the two groups for all subscales. CONCLUSION: CRD led to a lower severe complication rate and better short-term QoL than wide TME.

Small bowel obstruction, incisional hernia and survival after laparoscopic and open colonic resection (LAFA study).

BACKGROUND: Short-term advantages to laparoscopic surgery are well described. This study compared medium- to long-term outcomes of a randomized clinical trial comparing laparoscopic and open colonic resection for cancer. METHODS: The case notes of patients included in the LAFA study (perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care) were reviewed 2-5 years after randomization for incisional hernia, adhesional small bowel obstruction (SBO), overall survival, cancer recurrence and quality of life (QoL). The laparoscopic and open groups were compared irrespective of fast-track or standard perioperative care. RESULTS: Data on incisional hernias, SBO, survival and recurrence were available for 399 of 400 patients: 208 laparoscopic and 191 open resections. These outcomes were corrected for duration of follow-up. Median follow-up was 3·4 (i.q.r. 2·6-4·4) years. Multivariable regression analysis showed that open resection was a risk factor for incisional hernia (odds ratio (OR) 2·44, 95 per cent confidence interval (c.i.) 1·12 to 5·26; P = 0·022) and SBO (OR 3·70, 1·07 to 12·50; P = 0·039). There were no differences in overall survival (hazard ratio 1·10, 95 per cent c.i. 0·67 to 1·80; P = 0·730) or in cumulative incidence of recurrence (P = 0·514) between the laparoscopic and open groups. There were no measured differences in QoL in 281 respondents (P > 0·350 for all scales). CONCLUSION: Laparoscopic colonic surgery led to fewer incisional hernia and adhesional SBO events. REGISTRATION NUMBER: NTR222 (http://www.trialregister.nl).

Sarcopenia, sarcopenic obesity and mortality in older adults: results from the National Health and Nutrition Examination Survey III.

BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and quality, which accelerates with aging and is associated with functional decline. Rising obesity prevalence has led to a high-risk group with both disorders. We assessed mortality risk associated with sarcopenia and sarcopenic obesity in elders. METHODS: A subsample of 4652 subjects ≥60 years of age was identified from the National Health and Nutrition Examination Survey III (1988-1994), a cross-sectional survey of non-institutionalized adults. National Death Index data were linked to this data set. Sarcopenia was defined using a bioelectrical impedance formula validated using magnetic resonance imaging-measured skeletal mass by Janssen et al. Cutoffs for total skeletal muscle mass adjusted for height(2) were sex-specific (men: ≤5.75 kg/m(2); females ≤10.75 kg/m(2)). Obesity was based on % body fat (males: ≥27%, females: ≥38%). Modeling assessed mortality adjusting for age, sex, ethnicity (model 1), comorbidities (hypertension, diabetes, congestive heart failure, osteoporosis, cancer, coronary artery disease and arthritis), smoking, physical activity, self-reported health (model 2) and mobility limitations (model 3). RESULTS: Mean age was 70.6±0.2 years and 57.2% were female. Median follow-up was 14.3 years (interquartile range: 12.5-16.1). Overall prevalence of sarcopenia was 35.4% in women and 75.5% in men, which increased with age. Prevalence of obesity was 60.8% in women and 54.4% in men. Sarcopenic obesity prevalence was 18.1% in women and 42.9% in men. There were 2782 (61.7%) deaths, of which 39.0% were cardiovascular. Women with sarcopenia and sarcopenic obesity had a higher mortality risk than those without sarcopenia or obesity after adjustment (model 2, hazard ratio (HR): 1.35 (1.05-1.74) and 1.29 (1.03-1.60)). After adjusting for mobility limitations (model 3), sarcopenia alone (HR: 1.32 ((1.04-1.69) but not sarcopenia with obesity (HR: 1.25 (0.99-1.58)) was associated with mortality. For men, the risk of death with sarcopenia and sarcopenic obesity was nonsignificant in both model-2 (HR: 0.98 (0.77-1.25), and HR: 0.99 (0.79-1.23)) and model 3 (HR: 0.98 (0.77-1.24) and HR: 0.98 (0.79-1.22)). CONCLUSIONS: Older women with sarcopenia have an increased all-cause mortality risk independent of obesity.

[Tear in retinal pigment epithelium under anti-VEGF therapy for exudative age-related macular degeneration : function recovery under intensive therapy]. / Einriss im retinalen Pigmentepithel unter Anti-VEGF-Therapie bei der exsudativen altersbedingten Makuladegeneration : Funktionserholung unter intensiver Therapie.

This article reports the case of a 72-year-old woman with pigment epithelial detachment with occult choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD) which developed under anti-vascular endothelial growth factor (VEGF) therapy of a tear in the retinal pigment epithelium (RPE). In the area of free RPE autofluorescence was completely absent and the microperimetry in this area showed an absolute scotoma. The visual acuity was 0.1. After continuation of anti-VEGF therapy because of persistent subretinal and intraretinal fluid over 3 years an increased autofluorescence was observed and the microperimetry showed an increase in central retinal sensitivity. The central visual acuity improved to 0.5 and in this area a whitish subretinal tissue formed morphologically. In the spectral domain optical coherence tomography (SD-OCT) image this structure was hyperreflective which might suggest a certain regeneration process of the RPE under anti-VEGF-therapy.

[Endophthalmitis as a serious complication of intravitreal drug delivery]. / Endophthalmitis als schwere Komplikation der intravitrealen Medikamentengabe.

BACKGROUND: Endophthalmitis, regarded as a severe complication, can occur after intraocular injection of drugs (IVI). At present only few reports exist on the development of this disease, although recently the number of intraocular injections to treat especially age-related macular degenerations is increasing considerably. METHODS: In this paper we present our results of a retrospective study of 27 patients suffering from endophthalmitis after IVI. Treatment had been performed between January 2008 and March 2012. The indications for IVI were as follows: age-related macular degeneration 19, venous branch occlusion 1, diabethic retinopathies 6, uveitis 1. The following drugs were injected: bevacizumab in 8, Rranibizumab in 19 patients. The following data were assessed: incubation time, best corrected visual acuity that had been determined before treatment and later 3, 6 and 9 months after therapeutic vitrectomy. Additionally we describe the ophthalmoscopic changes and the results of bacteriological studies. RESULTS: Endophthalmitis was diagnosed 5.8 days after IVI on average. The vision of all patients had only been hand movements during the first examination. During the observation time the postoperative visual acuity could be improved only to 1/35 on average. During vitrectomy in 24 out of 27 patients a whitish retinal infiltration could be observed. 18 of 27 patients showed a hypopyon during slit lamp examination. 11 patients developed a retinal detachment and one eye had to be enucleated. CONCLUSIONS: Endophthalmitis must be regarded as a severe complication causing a high risk of retinal detachment with permanent loss of visual acuity. Retinal infiltrations and haemorrhages occur already in the early stages and cause finally a very poor prognosis. The incubation time as a rule amounts to 6 days. The increasing number of IVI and the high risk of damaged retinal structures due to intraocular infections should make postoperative retinal follow-up examinations mandatory, especially during the first 6 days.

Prolonged preoperative hospital stay is a risk factor for complications after emergency colectomy for severe colitis.

AIM: Risk factors for postoperative complications in patients undergoing emergency colectomy for severe colitis in inflammatory bowel disease have hardly been studied. Therefore, this study aimed to define predictors of a complicated postoperative course in these patients. METHOD: A retrospective review was performed of 71 consecutive patients who underwent emergency colectomy for severe colitis between 1999 and 2012 at a tertiary referral centre. Complications were graded according to the Clavien-Dindo classification. Patients with a complication Grade II or higher were compared with those with no complications or a Grade I complication. RESULTS: Nineteen patients (26.7%) had at least one postoperative complication classified as Clavien-Dindo Grade II or higher. In the group with postoperative complications, patients had a higher age (mean 45 vs 35 years, P = 0.020) and a higher body mass index (BMI) (mean 25.9 vs 21.0 kg/m(2), P = 0.006). Length of preoperative hospital stay (median 15 vs 6 days, P = 0.032) was longer in the group with postoperative complications. During the study period, the preoperative hospital stay decreased by 0.8 days per study year (95% CI 0.2-1.5 days, P < 0.001). This did not influence the complication rate over time, however. CONCLUSION: Factors increasing the risk of complications after emergency colectomy for severe colitis were a higher age, a higher BMI and a longer preoperative hospital stay.

Systematic review and meta-analysis of laparoscopic versus open colectomy with end ileostomy for non-toxic colitis.

BACKGROUND: This review compared short-term outcomes after laparoscopic versus open subtotal colectomy for acute, colitis medically refractory. METHODS: A systematic review of the literature was carried out using MEDLINE, Embase and the Cochrane databases. Overall study quality was assessed by the modified Methodological Index for Non-Randomized Studies (MINORS). Meta-analysis was performed for conversion, reoperation, wound infection, ileus, gastrointestinal bleeding, intra-abdominal abscess, postoperative length of stay and mortality. RESULTS: The search identified nine non-randomized studies: six cohort studies and three case-matched series, comprising 966 patients in total. The pooled conversion rate was 5·5 (95 per cent confidence interval (c.i.) 3·6 to 8·4) per cent in the laparoscopic group. The pooled risk ratio of wound infection was 0·60 (95 per cent c.i. 0·38 to 0·95; P = 0·03) and that of intra-abdominal abscess was 0·27 (0·08 to 0·91; P = 0·04), both in favour of laparoscopic surgery. Pooled risk ratios for other complications showed no significant differences. Length of stay was significantly shorter after laparoscopic subtotal colectomy, with a pooled mean difference of 3·17 (95 per cent c.i. 2·37 to 3·98) days (P < 0·001). CONCLUSION: Where the procedure can be completed laparoscopically, there may be short-term benefits over open colectomy for colitis. These results cannot be generalized to critically ill patients in need of an emergency subtotal colectomy.

Which fast track elements predict early recovery after colon cancer surgery?

AIM: It is questioned whether all separate fast track elements are essential for enhanced postoperative recovery. We aimed to determine which baseline characteristics and which fast track elements are independent predictors of faster postoperative recovery in patients undergoing resection for colon cancer. METHOD: Data from the LAFA trial database were used. In this trial, fast track care was compared with standard perioperative care in 400 patients undergoing laparoscopic or open surgery for colonic cancer. During admission 19 fast track elements per patient were prospectively evaluated and scored whether or not they were successfully applied. To identify predictive factors six baseline characteristics and those fast track items that were successfully achieved were entered in a univariate and multivariate linear regression analysis with total postoperative hospital stay (THS) as the primary outcome. RESULTS: In 400 patients, two baseline characteristics and two fast track elements were found to be significant independent predictors of THS: female sex [B = 0.85; 95% CI 0.75-0.96; reduction of 15% (CI 14-25%) in THS], laparoscopic resection [B = 0.85; 95% CI 0.75-0.96; reduction of 15% (CI 14-25%) in THS], 'normal diet at postoperative days 1, 2 and 3' [B = 0.70; 95% CI 0.61-0.81; reduction of 30% (CI 19-39%) in THS] and 'enforced mobilization at postoperative days 1, 2 and 3' [B = 0.68; 95% CI 0.59-0.80; reduction of 32% (CI 20-41%) in THS]. CONCLUSION: Evaluating only those fast track elements that were successfully achieved, enforced advancement of oral intake, early mobilization, laparoscopic surgery and female sex were independent determinants of early recovery.

Early, minimally invasive closure of anastomotic leaks: a new concept.

Chronic pelvic sepsis after ileoanal or coloanal anastomosis precludes ileostomy closure and, even if closure is ultimately possible, function of the neorectum is badly affected. Early closure of the anastomotic leak might prevent chronic pelvic sepsis and its adverse sequelae. In our experience of early closure in a consecutive group of six patients with a leaking low anastomosis (five with ileoanal pouch anastomosis and one after a low anterior resection), we were able to achieve anastomotic closure in five by means of initial endosponge therapy followed either by early suture (four patients) or endoscopic clip repair (one patient). Early minimally invasive closure of low anastomotic leaks is therefore possible provided that the para-anastomotic cavity is drained well prior to closure and the anastomosis is defunctioned.