EAES, SAGES, and ESCP rapid guideline: bowel preparation for minimally invasive colorectal resection.

BACKGROUND: Variation exists in practice pertaining to bowel preparation before minimally invasive colorectal surgery. A survey of EAES members prioritized this topic to be addressed by a clinical practice guideline. OBJECTIVE: The aim of the study was to develop evidence-informed clinical practice recommendations on the use of bowel preparation before minimally invasive colorectal surgery, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders. METHODS: This is a collaborative project of EAES, SAGES, and ESCP. We updated a previous systematic review and performed a network meta-analysis of interventions. We appraised the certainty of the evidence for each comparison, using the GRADE and CINeMA methods. A panel of general and colorectal surgeons, infectious diseases specialists, an anesthetist, and a patient representative discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost, and use of resources, moderated by a GIN-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey. RESULTS: The panel suggests either oral antibiotics alone prior to minimally invasive right colon resection or mechanical bowel preparation (MBP) plus oral antibiotics; MBP plus oral antibiotics prior to minimally invasive left colon and sigmoid resection, and prior to minimally invasive right colon resection when there is an intention to perform intracorporeal anastomosis; and MBP plus oral antibiotics plus enema prior to minimally invasive rectal surgery (conditional recommendations); and recommends MBP plus oral antibiotics prior to minimally invasive colorectal surgery, when there is an intention to localize the lesion intraoperatively (strong recommendation). The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/LwvKej . CONCLUSION: This guideline provides recommendations on bowel preparation prior to minimally invasive colorectal surgery for different procedures, using highest methodological standards, through a structured framework informed by key stakeholders. Guideline registration number PREPARE-2023CN045.

Patterns of Care for Patients With Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy at Predominately Academic Centers between 2016-2020: An NCDB Analysis.

Total neoadjuvant therapy (TNT) has emerged as the preferred approach for locally advanced rectal cancer (LARC), defined as T3/4 or any T with N+ disease. Our objective was to (1) determine the proportion of patients with LARC receiving TNT over time, (2) determine the most common method in which TNT is being delivered, and (3) determine what factors are associated with a greater likelihood of receiving TNT in the United States. Retrospective data was obtained from the National Cancer Database (NCDB) for patients diagnosed with rectal cancer between 2016 and 2020. Patients were excluded if they had M1 disease, T1-2 N0 disease, incomplete staging information, nonadenocarcinoma histology, received RT to a nonrectum site, or received a nondefinitive RT dose. Data were analyzed using linear regression, χ2 test, and binary logistic regression. Of the 26,375 patients included, most patients were treated at an academic facility (94.6%). Five thousand three (19.0%) patients received TNT, and 21,372 (81.0%) patients did not receive TNT. The proportion of patients receiving TNT increased significantly over time, from 6.1% in 2016 to 34.6% in 2020 (slope = 7.36, 95% CI 4.58-10.15, R2 = 0.96, P = .040). The most common TNT regimen was multiagent chemotherapy followed by long-course chemoradiation (73.2% of cases from 2016-2020). There was a significant increase in utilization of short-course RT as part of TNT from 2.8% in 2016 to 13.7% in 2020 (slope = 2.74, 95% CI 0.37-5.11, R2 = 0.82, P = .035). Factors associated with a lower likelihood of TNT usage included age >65, female gender, Black race, and T3 N0 disease. TNT use in the United States has increased significantly from 2016-2020, with approximately 34.6% of patients with LARC receiving TNT in 2020. The observed trend appears to be in line with the recent National Comprehensive Cancer Network guidelines recommending TNT as the preferred approach.

Cancer Survivors, Oncology, and Primary Care Perspectives on Survivorship Care: An Integrative Review.

PURPOSE: Evidence-based models of cancer survivorship care are lacking. Such models should take into account the perspectives of all stakeholders. The purpose of this integrative review is to examine the current state of the literature on cancer survivorship care from the cancer survivor, the oncology care team, and the primary care team perspectives. METHODS: Using defined inclusion and exclusion criteria, we conducted a literature search of PubMed, PsycINFO, CINAHL, and Scopus databases to identify relevant articles on the stakeholders' perspectives on cancer survivorship care published between 2010 and 2021. We reviewed and abstracted eligible articles to synthesize findings. RESULTS: A total of 21 studies were included in the review. Barriers to the receipt and provision of cancer survivorship care quality included challenges with communication, cancer care delivery, and knowledge. CONCLUSION: Persistent stakeholder-identified barriers continue to hinder the provision of quality cancer survivorship care. Improved communication, delivery of care, knowledge/information, and resources are needed to improve the quality of survivorship care. Novel models of cancer survivorship care that address the needs of survivors, oncology teams, and PCPs are needed.

Evaluation of Comparative Surveillance Strategies of Circulating Tumor DNA, Imaging, and Carcinoembryonic Antigen Levels in Patients With Resected Colorectal Cancer.

Importance: A circulating tumor DNA (ctDNA) assay (Signatera; Natera) has been marketed for use in the surveillance of resected colorectal cancer despite limited data supporting such practice. Objective: To compare a ctDNA assay with standard radiographic imaging and measurement of carcinoembryonic antigen (CEA) levels, per National Comprehensive Cancer Network guidelines, in the surveillance of resected colorectal cancer. Design, Setting, and Participants: This retrospective, single-center cohort study evaluated surveillance strategies of ctDNA, imaging, and measurement of CEA levels in patients with resected colorectal cancer from September 1, 2019, to November 30, 2021. Main Outcomes and Measures: The sensitivity and specificity of ctDNA, imaging, measurement of CEA levels, and combination of imaging plus measurement of CEA levels in detecting a confirmed recurrence of colorectal disease. A confirmed recurrence was defined as a positive ctDNA finding or a finding on imaging confirmed by biopsy, CEA level elevation, or subsequent tumor radiographic dynamics. Results: A total of 48 patients with curatively resected colorectal cancer satisfied the inclusion criteria for this study (28 men [58.3%]; median age, 60 [IQR, 34-85] years) and underwent surveillance by ctDNA, imaging, and measurement of CEA levels. Fifteen patients had disease recurrence during surveillance. Positive ctDNA findings confirmed disease recurrence in 8 patients; imaging, in 9 patients; CEA levels, in 3 patients; and combined imaging plus CEA levels, in 11 patients. Numerically, ctDNA did not perform better than imaging in detecting recurrence, with sensitivities of 53.3% (95% CI, 27.4%-77.7%) and 60.0% (95% CI, 32.9%-82.5%), respectively (P > .99). The combination of imaging plus measurement of CEA levels (sensitivity, 73.3% [95% CI, 44.8%-91.1%]) had a numerical advantage compared with ctDNA in identifying recurrence (P = .55). In addition, no significant difference was noted among ctDNA (median, 14.3 months), imaging (median, 15.0 months), or imaging plus measurement of CEA levels (median, 15.0 months) in the time to identify disease recurrence. Conclusions and Relevance: The findings of this cohort study suggest that ctDNA assay may not provide advantages as a surveillance strategy compared with standard imaging combined with CEA levels when performed per National Comprehensive Cancer Network guidelines.

Absorption, distribution, metabolism and excretion of molidustat in healthy participants.

The absorption, distribution, metabolism and excretion of molidustat were investigated in healthy male participants. In study 1, a mass balance study, radiolabelled molidustat 25 mg (3.57 MBq) was administered as an oral solution (n = 4). Following rapid absorption, molidustat-related radioactivity was predominantly distributed in plasma rather than in red blood cells. The total recovery of the administered radioactivity was 97.0%, which was mainly excreted renally (90.7%). Metabolite M-1, produced by N-glucuronidation, was the dominant component in plasma (80.2% of the area under the concentration-time curve for total radioactivity) and was primarily excreted via urine (~85% of dose). Only minor amounts of unchanged molidustat were excreted in urine (~4%) and faeces (~6%). Study 2 investigated the absolute bioavailability and pharmacodynamics of molidustat (part 1, n = 12; part 2, n = 16). Orally administered molidustat immediate release tablets had an absolute bioavailability of 59%. Following intravenous administration (1, 5 and 25 mg), total body clearance of molidustat was 28.7-34.5 L/h and volume of distribution at steady state was 39.3-50.0 L. All doses of molidustat transiently elevated endogenous erythropoietin levels, irrespective of the route of administration. Molidustat was considered safe and well tolerated at the administered doses.

Effects of oral iron and calcium supplement on the pharmacokinetics and pharmacodynamics of molidustat: an oral HIF-PH inhibitor for the treatment of renal anaemia.

PURPOSE: The present studies assessed the drug-drug interaction of molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, with iron and calcium supplements, which are common medications in patients with anaemia due to chronic kidney disease (CKD). METHODS: Forty-two healthy men received molidustat alone (fasted or fed) or combined with oral iron(II) or calcium(II), given immediately before or between 4 h before and 1 h after molidustat in three randomized, open-label, crossover studies (12-15 participants per study). Molidustat AUC and Cmax were assessed as the main pharmacokinetic parameters, and endogenous erythropoietin (EPO) was measured to evaluate pharmacodynamics. RESULTS: Depending on prandial state, concomitant intake of iron(II) reduced molidustat AUC and Cmax by 50-75% and 46-84%, respectively, and EPO AUC(0-24) and Cmax by 31-44% and 36-48%, respectively. The influence of iron(II) declined with increasing the time interval to the intake of molidustat, with reductions in molidustat AUC and Cmax of 9% and 10%, respectively, when iron(II) intake occurred 4 h before molidustat. Accordingly, effects on endogenous EPO were less pronounced with increased time separation between oral iron(II) and molidustat intake. Calcium(II) reduced molidustat AUC and Cmax by 15% and 47%, respectively, without influence on EPO response. All treatments were well tolerated. CONCLUSIONS: In contrast to concomitant oral intake of calcium, the effect of oral iron supplements on molidustat pharmacokinetics and pharmacodynamics should be considered, and the two agents should be administered with an appropriate time separation.

Alcohol dehydrogenase on inorganic powders: Zeta potential and particle agglomeration as main factors determining activity during immobilization.

Alcohol dehydrogenase from Saccharomyces cerevisiae was immobilized on different inorganic support materials, i.e. powders of Al2O3, SiC, TiO2 and YSZ-8, by covalent bonding and physical adsorption. The raw powders were characterized by scanning electron microscopy, BET surface area, particle size distribution and ζ-potential measurements. Enzyme activity retention, storage stability and recyclability were evaluated on the basis of the measured support material properties. Preliminary experiments showed that the buffer selection was a critical factor. The properties of both the enzyme and the powders varied considerably between the buffers used; namely Tris-HCl (100 mM, pH 7) and MES (40 mM, pH 6.5) buffers. The enzyme activity was higher and more stable in the MES buffer, whereas the commonly used Tris buffer was problematic due to apparent incompatibility with formaldehyde. In MES, the order of decreasing activity of covalently bonded enzyme was on SiC > YSZ-8 > Al2O3 > TiO2. The lower performance of TiO2 was ascribed to the negative ζ-potential of the material, which impeded an efficient immobilization. Particle agglomeration, caused by low colloidal stability of the particles in MES buffer, hampered the storage stability of the immobilized systems. The results from this study show the advantages and limitations of using nanoparticles as immobilization supports, and highlight which properties of nanoparticles must be considered to ensure an efficient immobilization.

Fecal Incontinence: Etiology, Diagnosis, and Management.

INTRODUCTION: Fecal incontinence is a debilitating condition affecting primarily the elderly. Many patients suffer in silence resulting in both underdiagnosis and undertreatment often culminating in an overall poor quality of life. METHODS: We sought to review the etiology, diagnosis, and treatment of fecal incontinence based on current literature. Additionally, newer treatment methods such as Solesta will be evaluated. RESULTS: There are many diagnostic modalities available to assess the degree and severity of the patient's incontinence; however, a thorough history and physical exam is critical. Initial attempts at treatment focus on medical management primarily through stool texture modification with the aid of bulking agents. Failure of medical therapy is often followed by a graded increase in the complexity and invasiveness of the available treatment options. The selection of the most appropriate surgical option, such as overlapping sphincteroplasty and neuromodulation, is multifactorial involving both surgeon and patient-related factors. Neuromodulation has received increased attention in the last decade due to its documented therapeutic success, and newer office-based procedures, such as the Solesta injection, are showing promising results in properly selected patients. Finally, diversion remains an option for select patients who have failed all other therapies. CONCLUSION: The etiology of fecal incontinence is multifactorial, involving a complex interplay between stool consistency and anatomic integrity. The diagnosis and treatment of fecal incontinence continue to evolve and are showing promising results.

Current status: new technologies for the treatment of patients with fecal incontinence.

Fecal incontinence is a frequent and debilitating condition that may result from a multitude of different causes. Treatment is often challenging and needs to be individualized. During the last several years, new technologies have been developed, and others are emerging from clinical trials to commercialization. Although their specific roles in the management of fecal incontinence have not yet been completely defined, surgeons have access to them and patients may request them. The purpose of this project is to put into perspective, for both the patient and the practitioner, the relative positions of new and emerging technologies in order to propose a treatment algorithm.

T-pouch: results of the first 10 years with a nonintussuscepting continent ileostomy.

BACKGROUND: Continent ileostomy is an alternative for patients who are either not candidates for an ileo-anal pullthrough or in whom an ileo-anal pullthrough failed. We previously described a new type of continent ileostomy (T-pouch) with a nonintussuscepting valve. OBJECTIVE: This study performed an outcomes analysis of the first 10 years with 40 patients. DESIGN: A prospective database of patients with a T-pouch from 2000 to 2010 was retrospectively analyzed. MAIN OUTCOME MEASURES: The primary outcomes measured were demographics and surgical recovery information and the functional data obtained via questionnaire: incontinence, difficulty of pouch intubation, restrictions (work, social, diet, and sexual), quality of health and life, and level of satisfaction with surgery, which were rated on a scale of 0 to 10. RESULTS: Twenty-three women and 17 men (mean age, 51.2) received a T-pouch. Median follow-up was 6.2 years (range, 0.8-11 years). Five patients (12.5%) experience a leak; 3 leaks were managed conservatively and/or with drain placement. Pouch intubations were done 4 times per day in a mean of 6.8 minutes; the insertion difficulty was rated as 2.5 of 10. Ninety-two percent achieved good continence. All quality-of-life and dysfunction/restriction scores showed significant improvement. Major abdominal surgeries for pouch-related reasons were needed in 30%; minor service operations of the skin-level stoma were needed in 25% of the patients. Of the patients, 87.5% would do the surgery again; 90% would recommend it to others with the same diagnosis. LIMITATIONS: This study was limited by the cohort size and the lack of long-term data. CONCLUSION: Ten years with 40 patients confirmed that creation of a T-pouch is complex but could be performed with an acceptable rate of complications. It dramatically improved functional outcomes; most notably, it improved fecal control and decreased social, sexual, and work restrictions.

Preservation of bowel and urinary continence in the management of locally recurrent rectal cancer.

BACKGROUND: The management of locally recurrent rectal cancer should achieve local tumor control and potentially improving disease-free and overall survival. Radical pelvic resection has traditionally been associated with permanent fecal and urinary diversion. However, as advanced techniques have evolved to allow restoration of intestinal and urinary continence, we reviewed the use of these techniques in patients with recurrent rectal cancer. METHODS: Patients with recurrent rectal cancer who underwent a resection at Norris Comprehensive Cancer Center between 1993 and 1999 were retrospectively reviewed. Data collected included demographic data, surgical and oncological history, patterns of recurrence, treatment modalities, and outcome. Follow-up data was obtained from the last clinic visit and/or tumor registry. RESULTS: Sixty-seven patients with locally recurrent rectal cancer (male/female 45/22, age 32-81 years) were included in the analysis. Continence was re-established in 22 (33%) patients, urinary continence was restored in 12 patients, and intestinal continuity in 14 patients (both in 4 patients). A temporary diverting ostomy was necessary in 5 out of 14 (36%) patients. Mortality was zero and morbidity was low and included two urinary leaks and one fecal leak all of which could be managed non-operatively. At a median follow-up of 16 months (range 5-55), 11 (50%) patients were still alive, 7 (31%) without evidence of disease. Comparison of the groups of patients either with or without continence preservation showed no statistically significant difference in disease-free survival and overall survival rates. High quality of life was achieved with restoration of continuity, no patient with restored continuity expressed a desire for a diversion. CONCLUSION: If an oncologically adequate resection of the recurrent rectal cancer can be performed without impairment of the pelvic floor integrity, continence preservation is feasible and results in good functional and oncological outcome.