Studies of diagnostic and surgical modalities in refractory constipation

ABSTRACT i) The aims were to: 1. Explore the diagnostic accuracy of anorectal manometry (AM) for diagnosis of dyssynergic defaecation; 2. Examine the yield of defaecography in patients with chronic constipation (CC) and healthy volunteers (HV) through systematic review and meta-analysis; 3. Examine the prevalence of defaecographic structural and functional abnormalities in a single-centre series of consecutive CC sufferers; 4. Explore outcomes of laparoscopic ventral mesh rectopexy (LVMR) for symptomatic intussusception; 5. Contribute to protocol development for a stepped-wedge randomized controlled trial of LVMR for intussusception. ii) Methods Epidemiological studies were conducted: 1. A diagnostic accuracy study of high-resolution AM to detect dyssynergic patterns of defaecation in HV and CC; 2. A systematic review and meta-analysis of studies reporting prevalence, definitions and cut-offs of defaecographic abnormalities in CC; 3. A cross-sectional study exploring the prevalence of defaecographic abnormalities in CC; 4. A systematic review and meta-analysis of studies reporting outcomes of hitching procedures (rectal suspension) for refractory constipation; 5. A large retrospective cohort study of patients undergoing LVMR for internal rectal prolapse (IRP); 6. The protocol for a randomized controlled trial (CapaCiTY 3) of LVMR for IRP was also developed. iii) Results 1. Only 9% of all participants exhibited the accepted ‘normal’ pattern of rectoanal coordination. A total of 94% of CC patients and 87% of HV had abnormal manometric patterns during simulated defaecation; some individual patterns discriminated CC from HV, e.g. the type IV pattern was modestly useful (i.e., PPV 70%, LR+ 2.3). 2. Multiple structural and functional defaecographic abnormalities may coexist in the same subject, with degree of overlap greater than previously recognized. The principal phenotypes encountered were normal defaecography (16%) and isolated functional abnormalities (13%), both significantly more prevalent in males than females. Coexistence of structural abnormalities was significantly more often encountered in females, reflecting global pelvic floor weakness. 3. A systematic review of evidence for the perioperative and long terms benefits and harms of rectal suspension procedures identified no high quality studies. The evidence base is characterised by observational studies of variable and often uncertain methodological quality. Definitions are poor, e.g. grading of complications was inconsistent. 4. Older age and previous urogenital prolapse surgery were independently associated with poorer quality of life at 12 months after LVMR. Mesh type was associated with mesh complication-free survival (p=0.001): polypropylene and titanium-coated lightweight polypropylene (TCLP) had better survival than polyester (HR 0.25 [95%CI0.11-0.54], 0.31 [95%CI0.09-1.06], respectively). Mesh type was strongly predictive of time to recurrence of prolapse (p<0.001), with polypropylene having the best recurrence-free survival, and TCLP the worst (HR 0.07 [95%CI0.02-0.34] vs. 2.93 [95%CI1.31-6.55], respectively). SRUS was independently associated with earlier recurrence of prolapse (HR 2.95, 95%CI1.05-8.27). iv) Conclusions 1. AM ‘push’ manoeuvre has limited utility for distinguishing between constipated and healthy subjects. 2. Pathologically significant structural abnormalities, as well as functional abnormalities, are common in CC patients. Since structural abnormalities cannot be evaluated using non-imaging test modalities (balloon expulsion and AM), defaecography should be considered first-line diagnostic test, if resources allow. 3. LVMR is clinically effective in the medium term for symptomatic relief of IRP. Choice of mesh strongly influences mesh complications and recurrence. CapaCiTY 3 might confirm (or refute) these findings

Kidney transplantation and withdrawal rates among wait-listed first-generation immigrants in Italy

Background: Multiple barriers diminish access to kidney transplantation (KT) in immigrant compared to non-immigrant populations. It is unknown whether immigration status reduces the likelihood of KT after wait-listing despite universal healthcare coverage with uniform access to transplantation. Methods: We retrospectively collected data of all adult waiting list (WL) registrants in Italy (2010-20) followed for 5 years until death, KT in a foreign center, deceased-donor kidney transplant (DDKT), living-donor kidney transplant (LDKT) or permanent withdrawal from the WL. We calculated adjusted relative probability of DDKT, LDKT and permanent WL withdrawal in different immigrant categories using competing-risks multiple regression models. Results: Patients were European Union (EU)-born (n = 21 624), Eastern European-born (n = 606) and non-European-born (n = 1944). After controlling for age, sex, blood type, dialysis vintage, case-mix and sensitization status, non-European-born patients had lower LDKT rates compared to other immigrant categories: LDKT adjusted relative probability of non-European-born vs. Eastern European-born 0.51 (95% CI: 0.33-0.79; P = 0.002); of non-European-born vs. EU-Born: 0.65 (95% CI: 0.47-0.82; P = 0.001). Immigration status did not affect the rate of DDKT or permanent WL withdrawal. Conclusions: Among EU WL registrants, non-European immigration background is associated with reduced likelihood of LDKT but similar likelihood of DDKT and permanent WL withdrawal. Wherever not available, new national policies should enable coverage of travel and medical fees for living-donor surgery and follow-up for non-resident donors to improve uptake of LDKT in immigrant patients, and provide KT education that is culturally competent, individually tailored and easily understandable for patients and their potential living donors

Surgery for constipation : systematic review and practice recommendations : Results II: Hitching procedures for the rectum (rectal suspension)

Aim To assess the outcomes of rectal suspension procedures (forms of rectopexy) in adults with chronic constipation. Method Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. Results Eighteen articles were identified, providing data on outcomes in 1238 patients. All studies reported only on laparoscopic approaches. Length of procedures ranged between 1.5 to 3.5 h, and length of stay between 4 to 5 days. Data on harms were inconsistently reported and heterogeneous, making estimates of harm tentative and imprecise. Morbidity rates ranged between 5–15%, with mesh complications accounting for 0.5% of patients overall. No mortality was reported after any procedures in a total of 1044 patients. Although inconsistently reported, good or satisfactory outcome occurred in 83% (74–91%) of patients; 86% (20–97%) of patients reported improvements in constipation after laparoscopic ventral mesh rectopexy (LVMR). About 2–7% of patients developed anatomical recurrence. Patient selection was inconsistently documented. As most common indication, high grade rectal intussusception was corrected in 80–100% of cases after robotic or LVMR. Healing of prolapse-associated solitary rectal ulcer syndrome occurred in around 80% of patients after LVMR. Conclusion Evidence supporting rectal suspension procedures is currently derived from poor quality studies. Methodologically robust trials are needed to inform future clinical decision making

Surgery versus stereotactic radiotherapy for treatment of pulmonary metastases. A systematic review of literature

It is not clear as to which is the best treatment among surgery and stereotactic radiotherapy (SBRT) for lung oligometastases. A systematic review of literature with a priori selection criteria was conducted on articles on the treatment of pulmonary metastases with surgery or SBRT. Only original articles with a population of patients of more than 50 were selected. After final selection, 61 articles on surgical treatment and 18 on SBRT were included. No difference was encountered in short-term survival between pulmonary metastasectomy and SBRT. In the long-term surgery seems to guarantee better survival rates. Mortality and morbidity after treatment are 0-4.7% and 0-23% for surgery, and 0-2% and 4-31% for SBRT. Surgical metastasectomy remains the treatment of choice for pulmonary oligometastases. Patients with metastatic cancer with a limited number of deposits may benefit from surgical removal or irradiation of tumor nodules in addiction to chemotherapy. Surgical resection has been demonstrated to improve survival and, in some cases, can be curative. Stereotactic radiotherapy is emerging as a less invasive alternative to surgery, but settings and implications of the two treatments are profoundly different. The two techniques show similar results in the short-term, with lower complications rates for radiotherapy, while in the long-term surgery seems to guarantee higher survival rates

Contemporary surgical practice in the management of anal fistula: results from an international survey

Background Management of anal fistula (AF) remains challenging with many controversies. The purpose of this study was to explore current surgical practice in the management of AF with a focus on technical variations among surgeons. Methods An online survey was conducted by inviting all surgeons and physicians on the membership directory of European Society of Coloproctology and American Society of Colon and Rectal Surgeons. An invitation was extended to others via social media. The survey had 74 questions exploring diagnostic and surgical techniques. Results In March 2018, 3572 physicians on membership directory were invited to take part in the study 510 of whom (14%) responded to the survey. Of these respondents, 492 (96%) were surgeons. Respondents were mostly colorectal surgeons (84%) at consultant level (84%), age ≥ 40 years (64%), practicing in academic (53%) or teaching (30%) hospitals, from the USA (36%) and Europe (34%). About 80% considered fistulotomy as the gold standard treatment for simple fistulas. Endorectal advancement flap was performed using partial- (42%) or full-thickness (44%) flaps. Up to 38% of surgeons performed ligation of the intersphincteric fistula tract (LIFT) sometimes with technical variations. Geographic and demographic differences were found in both the diagnostic and therapeutic approaches to AF. Declared rates of recurrence and fecal incontinence with these techniques were variable and did not correlate with surgeons’ experience. Only 1–4% of surgeons were confident in performing the most novel sphincter-preserving techniques in patients with Crohn’s disease. Conclusions Profound technical variations exist in surgical management of AF, making it difficult to reproduce and compare treatment outcomes among different centers

Effects of Extracorporeal Magnetic Stimulation in Fecal Incontinence.

Background: Fecal incontinence (FI) is a common condition that has devastating consequences for patients' QOL. In some patients, the conventional functional pelvic floor electrical stimulation has been effective but is an invasive and embarrassing treatment. The object of the study was to evaluate the feasibility of functional extracorporeal magnetic stimulation (FMS) in strengthening the pelvic floor muscles without an anal plug and the embarrassment of undressing. Materials and Methods: Thirty patients (26 female and 4 males) with FI were enrolled. All patients were assessed during a specialized coloproctology evaluation followed by endoanal ultrasonography and anorectal manometry. All patients underwent an FMS treatment once weekly for 8 weeks. Patients' outcome was assessed by the Cleveland Clinic Fecal Incontinence Score (CCFIS) and by the fecal incontinence QOL questionnaire (FIQL). Results: After 8 weeks, the number of solid and liquid stool leakage per week was significantly reduced (p<0.05) with a significant improvement of the CCFIS and of the FIQL (p<0.05). Moreover, the authors recorded a missed recruitment of the agonist and antagonists' defecation muscles. Conclusion: FMS is a safe, non-invasive and painless treatment for FI. It could be recommended for selected patients with non-surgical FI to ensure a rapid clinical improvement

Evaluation of bias correction methods for a multivariate drought index: case study of the Upper Jhelum Basin

Bias correction (BC) is often a necessity to improve the applicability of global and regional climate model (GCM and RCM, respectively) outputs to impact assessment studies, which usually depend on multiple potentially dependent variables. To date, various BC methods have been developed which adjust climate variables separately (univariate BC) or jointly (multivariate BC) prior to their application in impact studies (i.e., the component-wise approach). Another possible approach is to first calculate the multivariate hazard index from the original, biased simulations and bias-correct the impact model output or index itself using univariate methods (direct approach). This has the advantage of circumventing the difficulties associated with correcting the inter-variable dependence of climate variables which is not considered by univariate BC methods. Using a multivariate drought index (i.e., standardized precipitation evapotranspiration index – SPEI) as an example, the present study compares different state-of-the-art BC methods (univariate and multivariate) and BC approaches (direct and component-wise) applied to climate model simulations stemming from different experiments at different spatial resolutions (namely Coordinated Regional Climate Downscaling Experiment (CORDEX), CORDEX Coordinated Output for Regional Evaluations (CORDEX-CORE), and 6th Coupled Intercomparison Project (CMIP6)). The BC methods are calibrated and evaluated over the same historical period (1986–2005). The proposed framework is demonstrated as a case study over a transboundary watershed, i.e., the Upper Jhelum Basin (UJB) in the Western Himalayas. Results show that (1) there is some added value of multivariate BC methods over the univariate methods in adjusting the inter-variable relationship; however, comparable performance is found for SPEI indices. (2) The best-performing BC methods exhibit a comparable performance under both approaches with a slightly better performance for the direct approach. (3) The added value of the high-resolution experiments (CORDEX-CORE) compared to their coarser-resolution counterparts (CORDEX) is not apparent in this study.</p

Serum steroid profiling by isotopic dilution-liquid chromatography-mass spectrometry: comparison with current immunoassays and reference intervals in healthy adults.

BACKGROUND: The simultaneous, rapid and reliable measurement of a wide steroid panel is a powerful tool to unravel physiological and pathological hormone status. Clinical laboratories are currently dominated by high-throughput immunoassays, but these methods lack specificity due to cross-reactivity and matrix interferences. We developed and validated an isotopic dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method for the simultaneous measurement of cortisol, corticosterone, 11deoxycortisol, androstenedione, deoxycorticosterone (DOC), testosterone, 17OHprogesterone, dehydroepiandrosterone (DHEA) and progesterone in serum, and compared it to routine immunoassays employed in our laboratory. We also established adult reference intervals in 416 healthy subjects. METHODS: 0.9 ml of serum were spiked with labelled internal standards (IS) and extracted on C18 cartridges. Eluate was injected into a two-dimensional LC-system, purified in a perfusion column and separated on a C8 column during a 21 min gradient run. Analytes were revealed by atmospheric pressure chemical ionization (APCI) followed by multiple reaction monitoring (MRM) analysis. RESULTS: Of the four immunoassays compared with the ID-LC-MS/MS method, only the results of ElecsysE170 for cortisol, testosterone in males and progesterone>1 ng/ml were in agreement with ID-LC-MS/MS. ElecsysE170 for testosterone in females and progesterone<1 ng/ml, Immulite2000 for androstenedione, DSL-9000 for DHEA and 17OHP Bridge for 17OHprogesterone, respectively, showed poor agreement. Reference intervals and steroid age and fertility related fluctuations were established. CONCLUSION: Our ID-LC-MS/MS method proved to be reliable and sensitive in revealing steroid circulating concentrations in adults and in highlighting the limits of routine immunoassays at low concentrations