Interval Metastases After Neoadjuvant Chemoradiotherapy for Patients with Locally Advanced Esophageal Cancer: A Multicenter Observational Cohort Study.

BACKGROUND: Despite trimodality treatment, 10% to 20% of patients with esophageal cancer experience interval metastases after surgery. Restaging may identify patients who should not proceed to surgery, as well as a subgroup with limited metastases for whom long-term disease-control can be obtained. This study aimed to determine the proportion of patients with interval metastases after neoadjuvant chemoradiotherapy (nCRT) and to evaluate treatment and survival. METHODS: Patients who had cT2-4aN0-3M0 esophageal cancer treated with nCRT were identified from a trial database. Metastases detected up to 14 weeks after nCRT on 18F-FDG-PET/CT or during surgery were categorized as oligometastases (≤3 lesions located in one single organ or one extra-regional lymph node station) or as non-oligometastases. The primary outcome was the proportion of patients with metastases after nCRT. The secondary outcomes were overall survival (OS) and the site and treatment of metastases. RESULTS: Between 2013 and 2021, 973 patients received nCRT, and 10.3% had interval metastases. Of 100 patients, 30 (30%) had oligometastases, located mostly in non-regional lymph nodes (33.3%) or bones (26.7%). The median OS of this group was 13.8 months (95% confidence interval [CI] 9.2-27.1 months). Of 30 patients, 12 (40%) with oligometastases underwent potentially curative treatment, with a median OS of 22.8 months (95% CI 10.4-NA). The patients with non-oligometastases underwent mostly systemic therapy or BSC and had a median OS of 9 months (95% CI 7.4-10.9 months). CONCLUSIONS: Interval metastases were detected in about 10% of patients after nCRT, underscoring the importance of re-staging with 18F-FDG-PET/CT for those who proceed to surgery. A favorable survival might be accomplished for a subgroup of patients with oligometastases.

Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting.

BACKGROUND: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. METHODS: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either 'node-picking' (the removal of an individual LLN) or 'partial regional node dissection' (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those  undergoing only rectal resection. RESULTS: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7-3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2-2.5, p = 0.874). CONCLUSION: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.

Learning Curves of Ivor Lewis Totally Minimally Invasive Esophagectomy by Hospital and Surgeon Characteristics: A Retrospective Multinational Cohort Study.

OBJECTIVE: To describe the pooled learning curves of Ivor Lewis totally minimally invasive esophagectomy (TMIE) in hospitals stratified by predefined hospital- and surgeon-related factors. BACKGROUND: Ivor Lewis (TMIE is known to have a long learning curve which is associated with considerable learning associated morbidity. It is unknown whether hospital and surgeon characteristics are associated with more efficient learning. METHODS: A retrospective analysis of prospectively collected data of consecutive Ivor Lewis TMIE patients in 14 European hospitals was performed. Outcome parameters used as proxy for efficient learning were learning curve length, learning associated morbidity, and the plateau level regarding anastomotic leakage and textbook outcome. Pooled incidences were plotted for the factor-based subgroups using generalized additive models and 2-phase models. Casemix predicted outcomes were plotted and compared with observed outcomes. The investigated factors included annual volume, TMIE experience, clinic visits, courses and fellowships followed, and proctor supervision. RESULTS: This study included 2121 patients. The length of the learning curve was shorter for centers with an annual volume >50 compared to centers with an annual volume <50. Analysis with an annual volume cut-off of 30 cases showed similar but less pronounced results. No outcomes suggesting more efficient learning were found for longer experience as consultant, visiting an expert clinic, completing a minimally invasive esophagectomy fellowship or implementation under proctor supervision. CONCLUSIONS: More efficient learning was observed in centers with higher annual volume. Visiting an expert clinic, completing a fellowship, or implementation under a proctor's supervision were not associated with more efficient learning.

Colonoscopic-Assisted Laparoscopic Wedge Resection for Colonic Lesions: A Prospective Multicenter Cohort Study (LIMERIC-Study).

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. SUMMARY BACKGROUND DATA: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. METHODS: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. RESULTS: Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. CONCLUSIONS: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.

Decompressing Stoma a s 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.

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. METHODS: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. DISCUSSION: If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care.

Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial.

BACKGROUND: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. METHODS: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. FINDINGS: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). INTERPRETATION: Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. FUNDING: Vifor Pharma.

Systematic review of sentinel lymph node mapping procedure in colorectal cancer.

BACKGROUND: The clinical impact of sentinel lymph node (SN) biopsy in colorectal cancer is still controversial. The aim of our study was to determine the accuracy of this procedure from published data and to identify factors that contribute to the conflicting reports. METHODS: A systematic search of the Medline, Embase, and Cochrane databases up to July 2011 revealed 98 potentially eligible studies, of which 57 were analyzed including 3,934 patients (3,944 specimens). RESULTS: The pooled SN identification rate was 90.7% (95% CI 88.2-93.3), with a significant higher identification rate in studies including more than 100 patients or studies using the ex vivo SN technique. The pooled sensitivity of the SN procedure was 69.6% (95% CI 64.7-74.6). Including the immunohistochemical findings increased the pooled sensitivity of SN procedure to 80.2% (95% CI 4.7-10.7). Subgroups with significantly higher sensitivity could be identified: ≥4 SNs versus <4 SNs (85.2 vs. 66.3%, p = 0.003), colon versus rectal cancer (77.6 vs. 65.7%, p = 0.04), early T1 or T2 versus advanced T3 or T4 carcinomas (93.4 vs. 58.8%, p = 0.01). Serial sectioning and immunohistochemistry resulted in a mean upstaging of 18.9% (range 0-50%). True upstaging defined as micrometastases (pN1mi+) rather than isolated tumor cells (pN0itc+) was 7.7%. CONCLUSIONS: The SN procedure in colorectal cancer has an overall sensitivity of 70%, with increased sensitivity and refined staging in early-stage colon cancer. Because the ex vivo SN mapping is an easy technique it should be considered in addition to conventional resection in colon cancer.

The effect of colonoscopic tattooing on lymph node retrieval and sentinel lymph node mapping.

BACKGROUND: In colorectal cancer (CRC), colonoscopic tattooing is performed to mark the tumor site before laparoscopic surgery. OBJECTIVE: To determine whether colonoscopic tattooing can be used to refine staging accuracy by increasing the lymph node (LN) yield per specimen and to determine its accuracy as a sentinel LN procedure. DESIGN: Retrospective, case-control study. All LNs were microscopically examined for the presence of carbon particles. SETTING: A university hospital and a teaching hospital. PATIENTS: A consecutive series of 95 tattooed patients who had surgery for CRC between 2005 and 2009. A series of 210 non-tattooed patients who had surgery in the same time period served as controls. MAIN OUTCOME MEASUREMENTS: Total number of LNs retrieved, detection rate, and sensitivity of tattooing as a sentinel node procedure. RESULTS: A higher LN yield was observed in patients with preoperative tattooing, median (interquartile range) 15 (10-20) versus 12 (9-16), (P = .014). In multivariable analysis, the presence of carbon-containing LNs was an independent predictive factor for a higher LN yield (P = .002). The detection rate was 71%, with a median of 5 carbon-containing LNs per specimen. If preoperative tattooing was used for sentinel node mapping, the overall accuracy of predicting LN status was 94%. In the 24 N1 cases, there were 4 false-negative procedures (sensitivity 83%). LIMITATIONS: Retrospective series. CONCLUSION: After tattooing of CRC, the LN yield was higher than in a control group, and it could be used as a sentinel node procedure with acceptable accuracy rates. Because LN yield and sentinel node mapping are associated with improved diagnostic accuracy of LN involvement, preoperative tattooing can refine staging.

Body Composition Is a Predictor for Postoperative Complications After Gastrectomy for Gastric Cancer: a Prospective Side Study of the LOGICA Trial.

PURPOSE: There is a lack of prospective studies evaluating the effects of body composition on postoperative complications after gastrectomy in a Western population with predominantly advanced gastric cancer. METHODS: This is a prospective side study of the LOGICA trial, a multicenter randomized trial on laparoscopic versus open gastrectomy for gastric cancer. Trial patients who received preoperative chemotherapy followed by gastrectomy with an available preoperative restaging abdominal computed tomography (CT) scan were included. The CT scan was used to calculate the mass (M) and radiation attenuation (RA) of skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). These variables were expressed as Z-scores, depicting how many standard deviations each patient's CT value differs from the sex-specific study sample mean. Primary outcome was the association of each Z-score with the occurrence of a major postoperative complication (Clavien-Dindo grade ≥ 3b). RESULTS: From 2015 to 2018, a total of 112 patients were included. A major postoperative complication occurred in 9 patients (8%). A high SM-M Z-score was associated with a lower risk of major postoperative complications (RR 0.47, 95% CI 0.28-0.78, p = 0.004). Furthermore, high VAT-RA Z-scores and SAT-RA Z-scores were associated with a higher risk of major postoperative complications (RR 2.82, 95% CI 1.52-5.23, p = 0.001 and RR 1.95, 95% CI 1.14-3.34, p = 0.015, respectively). VAT-M, SAT-M, and SM-RA Z-scores showed no significant associations. CONCLUSION: Preoperative low skeletal muscle mass and high visceral and subcutaneous adipose tissue radiation attenuation (indicating fat depleted of triglycerides) were associated with a higher risk of developing a major postoperative complication in patients treated with preoperative chemotherapy followed by gastrectomy.

Laparoscopy in combination with fast track multimodal management is the best perioperative strategy in patients undergoing colonic surgery: a randomized clinical trial (LAFA-study).

OBJECTIVE: To investigate which perioperative treatment, ie, laparoscopic or open surgery combined with fast track (FT) or standard care, is the optimal approach for patients undergoing segmental resection for colon cancer. SUMMARY BACKGROUND DATA: Important developments in elective colorectal surgery are the introduction of laparoscopy and implementation of FT care, both focusing on faster recovery. METHODS: In a 9-center trial, patients eligible for segmental colectomy were randomized to laparoscopic or open colectomy, and to FT or standard care, resulting in 4 treatment groups. Primary outcome was total postoperative hospital stay (THS). Secondary outcomes were postoperative hospital stay (PHS), morbidity, reoperation rate, readmission rate, in-hospital mortality, quality of life at 2 and 4 weeks, patient satisfaction and in-hospital costs. Four hundred patients were required to find a minimum difference of 1 day in hospital stay. RESULTS: Median THS in the laparoscopic/FT group was 5 (interquar-tile range: 4-8) days; open/FT 7 (5-11) days; laparoscopic/standard 6 (4.5-9.5) days, and open/standard 7 (6-13) days (P < 0.001). Median PHS in the laparoscopic/FT group was 5 (4-7) days; open/FT 6 (4.5-10) days; laparoscopic/standard 6 (4-8.5) days and open/standard 7 (6-10.5) days (P < 0.001). Secondary outcomes did not differ significantly among the groups. Regression analysis showed that laparoscopy was the only independent predictive factor to reduce hospital stay and morbidity. CONCLUSIONS: Optimal perioperative treatment for patients requiring segmental colectomy for colon cancer is laparoscopic resection embedded in a FT program. If open surgery is applied, it is preferentially done in FT care. This study was registered under NTR222 (www.trialregister.nl).

Updated protocol of the SANO trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer.

BACKGROUND: The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant chemoradiotherapy. The last patient with a clinically complete response is expected to be included in May 2021. The purpose of this update is to present all amendments to the SANO trial protocol as approved by the Institutional Research Board (IRB) before accrual is completed. DESIGN: The SANO trial protocol has been published ( https://doi.org/10.1186/s12885-018-4034-1 ). In this ongoing, phase-III, non-inferiority, stepped-wedge, cluster randomised controlled trial, patients with cCR (i.e. after neoadjuvant chemoradiotherapy no evidence of residual disease in two consecutive clinical response evaluations [CREs]) undergo either active surveillance or standard oesophagectomy. In the active surveillance arm, CREs are repeated every 3 months in the first year, every 4 months in the second year, every 6 months in the third year, and yearly in the fourth and fifth year. In this arm, oesophagectomy is offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant metastases. The primary endpoint is overall survival. UPDATE: Amendments to the study design involve the first cluster in the stepped-wedge design being partially randomised as well and continued accrual of patients at baseline until the predetermined number of patients with cCR is reached. Eligibility criteria have been amended, stating that patients who underwent endoscopic treatment prior to neoadjuvant chemoradiotherapy cannot be included and that patients who have highly suspected residual tumour without histological proof can be included. Amendments to the study procedures include that patients proceed to the second CRE if at the first CRE the outcome of the pathological assessment is uncertain and that patients with a non-passable stenosis at endoscopy are not considered cCR. The sample size was recalculated following new insights on response rates (34% instead of 50%) and survival (expected 2-year overall survival of 75% calculated from the moment of reaching cCR instead of 3-year overall survival of 67% calculated from diagnosis). This reduced the number of required patients with cCR from 264 to 224, but increased the required inclusions from 480 to approximately 740 patients at baseline. CONCLUSION: Substantial amendments were made prior to closure of enrolment of the SANO trial. These amendments do not affect the outcomes of the trial compared to the original protocol. The first results are expected late 2023. If active surveillance plus surgery as needed after neoadjuvant chemoradiotherapy for oesophageal cancer leads to non-inferior overall survival compared to standard oesophagectomy, active surveillance can be implemented as a standard of care.

A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial).

BACKGROUND: Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects. METHODS: A randomized multicenter pragmatic clinical trial comparing two treatment strategies for uncomplicated acute diverticulitis. I) A conservative strategy with antibiotics: hospital admission, supportive measures and at least 48 hours of intravenous antibiotics which subsequently are switched to oral, if tolerated (for a total duration of antibiotic treatment of 10 days). II) A liberal strategy without antibiotics: admission only if needed on clinical grounds, supportive measures only. Patients are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by radiological imaging. Only patients with stages 1a and 1b according to Hinchey's classification or "mild" diverticulitis according to the Ambrosetti criteria are included. The primary endpoint is time-to-full recovery within a 6-month follow-up period. Full recovery is defined as being discharged from the hospital, with a return to pre-illness activities, and VAS score below 4 without the use of daily pain medication. Secondary endpoints are proportion of patients who develop complicated diverticulitis requiring surgery or non-surgical intervention, morbidity, costs, health-related quality of life, readmission rate and acute diverticulitis recurrence rate. In a non-inferiority design 264 patients are needed in each study arm to detect a difference in time-to-full recovery of 5 days or more with a power of 85% and a confidence level of 95%. With an estimated one percent of patients lost to follow up, a total of 533 patients will be included. CONCLUSION: A clinically relevant difference of more than 5 days in time-to-full recovery between the two treatment strategies is not expected. The liberal strategy without antibiotics and without the strict requirement for hospital admission is anticipated to be more a more cost-effective approach. TRIAL REGISTRATION NUMBER: NCT01111253.

Comparison of Decompressing Stoma vs Stent as a Bridge to Surgery for Left-Sided Obstructive Colon Cancer.

Importance: Bridge to elective surgery using self-expandable metal stent (SEMS) placement is a debated alternative to emergency resection for patients with left-sided obstructive colon cancer because of oncologic concerns. A decompressing stoma (DS) might be a valid alternative, but relevant studies are scarce. Objective: To compare DS with SEMS as a bridge to surgery for nonlocally advanced left-sided obstructive colon cancer using propensity score matching. Design, Setting, and Participants: This national, population-based cohort study was performed at 75 of 77 hospitals in the Netherlands. A total of 4216 patients with left-sided obstructive colon cancer treated from January 1, 2009, to December 31, 2016, were identified from the Dutch Colorectal Audit and 3153 patients were studied. Additional procedural and intermediate-term outcome data were retrospectively collected from individual patient files, resulting in a median follow-up of 32 months (interquartile range, 15-57 months). Data were analyzed from April 7 to October 28, 2019. Exposures: Decompressing stoma vs SEMS as a bridge to surgery. Main Outcomes and Measures: Primary anastomosis rate, postresection presence of a stoma, complications, additional interventions, permanent stoma, locoregional recurrence, disease-free survival, and overall survival. Propensity score matching was performed according to age, sex, body mass index, American Society of Anesthesiologists score, prior abdominal surgery, tumor location, pN stage, cM stage, length of stenosis, and year of resection. Results: A total of 3153 of the eligible 4216 patients were included in the study (mean [SD] age, 69.7 [11.8] years; 1741 [55.2%] male); after exclusions, 443 patients underwent bridge to surgery (240 undergoing DS and 203 undergoing SEMS). Propensity score matching led to 2 groups of 121 patients each. Patients undergoing DS had more primary anastomoses (104 of 121 [86.0%] vs 90 of 120 [75.0%], P = .02), more postresection stomas (81 of 121 [66.9%] vs 34 of 117 [29.1%], P < .001), fewer major complications (7 of 121 [5.8%] vs 18 of 118 [15.3%], P = .02), and more subsequent interventions, including stoma reversal (65 of 113 [57.5%] vs 33 of 117 [28.2%], P < .001). After DS and SEMS, the 3-year locoregional recurrence rates were 11.7% for DS and 18.8% for SEMS (hazard ratio [HR], 0.62; 95% CI, 0.30-1.28; P = .20), the 3-year disease-free survival rates were 64.0% for DS and 56.9% for SEMS (HR, 0.90; 95% CI, 0.61-1.33; P = .60), and the 3-year overall survival rates were 78.0% for DS and 71.8% for SEMS (HR, 0.77; 95% CI, 0.48-1.22; P = .26). Conclusions and Relevance: The findings suggest that DS as bridge to resection of left-sided obstructive colon cancer is associated with advantages and disadvantages compared with SEMS, with similar intermediate-term oncologic outcomes. The existing equipoise indicates the need for a randomized clinical trial that compares the 2 bridging techniques.

Improving Outcomes in Oncological Colorectal Surgery by Prehabilitation.

INTRODUCTION: The cornerstone in the treatment of colorectal cancer is surgery. A surgical event poses a significant risk of decreased functional decline and impaired health-related quality of life. Prehabilitation is defined as the multimodal preoperative enhancement of a patient's condition. It may serve as a strategy to improve postoperative outcomes. Prehabilitation requires a multidisciplinary effort of medical health care professionals and a behavioral change of the patient. METHODS: The goal of prehabilitation is threefold: (1) to reduce postoperative complications, (2) to enhance and accelerate the recovery of the patient, and (3) to improve overall quality of life. In this article, we introduce the FIT model illustrating a possible framework toward the implementation of both evidence-based and tailor-made prehabilitation for patients undergoing surgery for colorectal cancer. RESULTS: The model is composed of three pillars: "facts" (how to screen patients and evidence on what content to prescribe), "integration" (data of own questionnaires assessing motivation of patients and specialists), and finally "tools" (which outcome measurements to use). DISCUSSION: Developing implementable methods and defining standardized outcome instruments will help establish a solid base for patient-centered prehabilitation programs. Any party introducing prehabilitation requiring multidisciplinary teamwork and behavioral change can potentially use this framework.

Fit4SurgeryTV At-home Prehabilitation for Frail Older Patients Planned for Colorectal Cancer Surgery: A Pilot Study.

OBJECTIVE: The preoperative phase is a potential window of opportunity. Although frail elderly patients are known to be more prone to postoperative complications, they are often not considered capable of accomplishing a full prehabilitation program. The aim of this study was to assess the feasibility of Fit4SurgeryTV, an at-home prehabilitation program specifically designed for frail older patients with colorectal cancer. DESIGN: The Fit4SurgeryTV program consisted of a daily elderly adapted computer-supported strength training workout and two protein-rich meals. Frail patients 70 yrs or older with colorectal cancer were included. The program was considered feasible if 80% of the patients would be able to complete 70% of the program. RESULTS: Fourteen patients (median age, 79 yrs; 5 males) participated. At baseline, 86% patients were physically impaired and 64% were at risk for malnourishment. The median duration of the program was 26 days. The program was feasible as patients followed the exercises for 6 (86%) of 7 days and prepared the recipes 5 (71%) of 7 d/wk. Patients specifically appreciated at-home exercises. CONCLUSIONS: This study showed that at-home prehabilitation in frail older patients with colorectal cancer is feasible. As a result, patients might be fitter for surgery and might recover faster. The perioperative period could serve as a pivotal time point in reverting complications of immobility.

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial).

BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction. The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register NTR1150.

Oral Nutrition as a Form of Pre-Operative Enhancement in Patients Undergoing Surgery for Colorectal Cancer: A Systematic Review.

BACKGROUND: Nutritional status has major impacts on the outcome of surgery, in particular in patients with cancer. The aim of this review was to assess the merit of oral pre-operative nutritional support as a part of prehabilitation in patients undergoing surgery for colorectal cancer. METHODS: A systematic literature search and meta-analysis was performed according to the Preferred Reporting of Systematic Reviews and Meta-Analyses (PRISMA) recommendations in order to review all trials investigating the effect of oral pre-operative nutritional support in patients undergoing colorectal surgery. The primary outcome was overall complication rate. Secondary outcomes were incision infection rate, anastomotic leakage rate, and length of hospital stay. RESULTS: Five randomized controlled trials and one controlled trial were included. The studies contained a total of 583 patients with an average age of 63 y (range 23-88 y), of whom 87% had colorectal cancer. Malnourishment rates ranged from 8%-68%. All investigators provided an oral protein supplement. Overall patient compliance rates ranged from 72%-100%. There was no significant reduction in the overall complication rate in the interventional groups (odds ratio 0.82; 95% confidence interval 0.52 - 1.25). CONCLUSION: Current studies are too heterogeneous to conclude that pre-operative oral nutritional support could enhance the condition of patients undergoing colorectal surgery. Patients at risk have a relatively lean body mass deficit (sarcopenia) rather than an absolute malnourished status. Compliance is an important element of prehabilitation. Targeting patients at risk, combining protein supplements with strength training, and defining standardized patient-related outcomes will be essential to obtain satisfactory results.

Diagnostic choices and clinical outcomes in octogenarians and nonagenarians with iron-deficiency anemia in the Netherlands.

OBJECTIVES: To evaluate current clinical practice for octogenarians with iron-deficiency anemia (IDA) by assessing referral patterns, diagnostic choices, clinical consequences of omission of endoscopy, and risks and benefits of IDA-related surgery. DESIGN: Chart review. SETTING: A regional hospital-based laboratory in the Netherlands between January 2008 and December 2010. PARTICIPANTS: All individuals aged 80 and older with newly ascertained IDA. MEASUREMENTS: IDA was defined as a hemoglobin level of 11.1 g/dL or less and a ferritin level of 25 µg/L or less. RESULTS: Four hundred seventy-one participants were newly diagnosed with IDA during the study period (median age 85.4), 276 of whom (59%) did not undergo any diagnostic procedures for IDA. A cause of anemia was identified during the initial examination in 50% of the 205 investigated participants, including nine (4%) upper and 37 (18%) lower gastrointestinal malignancies. Another 24 malignancies were identified during follow-up, of which 16 were in the gastrointestinal tract, primarily in participants for whom the initial diagnostic examination was limited or omitted. Perioperative mortality was 15% in individuals with colon cancer. Median survival for participants with colon cancer was 2.2 years, and the survival benefit of surgery over supportive care was not apparent until 1.3 years after ascertainment of IDA. CONCLUSION: The omission of endoscopy for IDA and the omission of surgery for colon cancer occur frequently in octogenarians and seem appropriate in the presence of significant comorbidity and in cases in which there is limited life expectancy. Further research is needed to determine which baseline factors should guide decision-making to optimize treatment outcomes and quality of life.