Two-row, three-row or powered circular stapler, which to choose when performing colorectal anastomosis? A systematic review and meta-analysis.

PURPOSE: Three types of circular staplers can be used to perform a colorectal anastomosis: two-row (MCS), three-row (TRCS) and powered (PCS) devices. The objective of this meta-analysis has been to provide the existing evidence on which of these circular staplers would have a lower risk of presenting a leak (AL) and/or anastomotic bleeding (AB). METHODS: An in-depth search was carried out in the electronic bibliographic databases Embase, PubMed and SCOPUS. Observational studies were included, since randomized clinical trials comparing circular staplers were not found. RESULTS: In the case of AL, seven studies met the inclusion criteria in the PCS group and four in the TRCS group. In the case of AB, only four studies could be included in the analysis in the PCS group. The AL OR reported for PCS was 0.402 (95%-confidence interval (95%-CI): 0.266-0.608) and for AB: 0.2 (95% CI: 0.08-0.52). The OR obtained for AL in TRCS was 0.446 (95%-CI: 0.217 to 0.916). Risk difference for AL in PCS was - 0.06 (95% CI: - 0.07 to - 0.04) and in TRCS was - 0.04 (95%-CI: - 0.08 to - 0.01). Subgroup analysis did not report significant differences between groups. On the other hand, the AB OR obtained for PCS was 0.2 (95% CI: 0.08-0.52). In this case, no significant differences were observed in subgroup analysis. CONCLUSION: PCS presented a significantly lower risk of leakage and anastomotic bleeding while TRCS only demonstrated a risk reduction in AL. Risk difference of AL was superior in the PCS than in TRCS.

Anatomical sphincteroplasty as a surgical treatment for faecal incontinence: proposal for a global anatomical reconstructive surgical procedure and results from a case series.

The aim of this study is to describe the technical details and clinical and functional results of anatomical sphincteroplasty as a global reconstructive surgery for the treatment of faecal incontinence caused by anal sphincter lesions. This was a prospective, longitudinal study that included patients who underwent the anatomical sphincteroplasty procedure described here to treat complete sphincter damage. We have described the different technical steps in detail. We evaluated the intraoperative and postoperative complications rate, Cleveland Clinic Score (CCS), a modification of the CCS that included soiling (mCCS), the Faecal Incontinence Quality of Life Scale (FIQLS), and patient satisfaction. An endoanal ultrasound and anorectal manometric study were performed in all the patients. Forty-four patients were included with a mean of 40.5 months follow-up. The CCS reduced from 15 to 3.3 points and the mCCS from 18.5 to 4.5 points over the study period; p < 0.001. Excellent or good results were achieved in 93% of cases. Endoanal ultrasounds showed a good sphincter repair in 66% of the cases. Anorectal manometry showed an increase in the mean maximal resting pressure from 27.6 mmHg to 41.7 mmHg and of the maximal squeeze pressure from 57.9 to 93 mmHg (p < 0.001) with respect to the preoperative values. Anatomical sphincteroplasty is a surgical proposal for the global anatomical reconstruction of anal sphincter lesions, even in cases of very severe damage. The procedure is safe and produced excellent clinical and functional results after a medium-term follow-up.

An unusual case of proctalgia: kerosene rectal injury.

Kerosene has been described as an uncommon burn injury agent(1). We report a case of a 47-year-old male who presented to the Emergency Department with proctalgia after self-administration of an unknown enema in the context of cocaine intoxication. Physical examination revealed severe perianal inflammation (Figure 1.A) without suppuration and computerized tomography (CT) scan showed free air in mesorectum and retroperitoneum without intraperitoneal free air or fluid (Figure 1.B and 1.C). Rigid rectoscopy demostrated erythematous rectal mucosa without perforation. Subsequently, perineal drainage and debridement were performed. On the fifth postoperative day, the patient reported worsening proctalgia. Examination under anesthesia revealed the presence of new-onsetanal ulcers (Figure 1.D), rigid rectoscopy identified deep ulcers limited to the rectal mucosa and colonoscopy ruled out colon involvement. During reevaluation, the patient disclosed the use of sailboat engine lubrican as the enema, with kerosene being one of its components. These findings were consistent with rectal burn injuries resulting from exposure to kerosene. A laparoscopic end-loop colostomy was performed without any postoperative complications. Follow-up examinations with rigid rectoscopy showed improvement of rectal ulcers (Figure 1.E and 1.F). To our knowledge, this is the first case of rectal burn injuries after kerosene exposure(2,3). Aggressive washout, early colostomy and serial follow-up scopes are key components in the management of these rare injuries.

Does month of birth influence colorectal cancer prognosis?

PURPOSE: The main aim of this study was to identify a possible association between month of birth of colorectal cancer (CRC) patients and overall survival (OS) or disease-free survival (DFS). METHODS: This observational study included all consecutive adult patients diagnosed with CRC undergoing oncological surgery from January 2005 to December 2019 with a minimum follow-up of 10 years. The outcome variables were locoregional recurrence, death due to cancer progression, OS and DFS. Non-supervised learning techniques (K-means) were conducted to identify groups of months with similar oncologic outcomes. Finally, OS and DFS were analysed using Kaplan-Meier and Cox regression tests. The model was calibrated with resampling techniques and subsequently a cross-validation was performed. RESULTS: A total of 2520 patients were included. Three birth month groups with different oncologic outcomes were obtained. Survival analysis showed between-group differences in OS (p < 0.001) and DFS (p = 0.03). The multivariable Cox proportional hazards model identified the clusters obtained as independent prognostic factors for OS (p < 0.001) and DFS (p = 0.031). CONCLUSION: There is an association between month of birth and oncologic outcomes of CRC. Patients born in the months of January, February, June, July, October and December had better OS and DFS than those born in different months of the year.

A diagnostic challenge: chronic cutaneous ulcers as an isolated clinical finding in metastatic Crohn's disease.

Metastasic Crohn disease (MCD) is the most uncommon cutaneous manifestation of Crohn disease. The actual incidence is not clear. There are fewer than 200 cases described in the literature. We report a case of 21 years-old girl that came to our emergency care with large exudative ulcers in the inguinal folds, the vulva, the perianal region and the popliteal fossae. Histopathological examination of the ulcers revealed a non-caseating granulomatous inflammation with abundant multinucleated giant cells and intense lymphocytic infiltrate. Colonoscopy, contrast study of the small bowel and video capsule endoscopy were carried out without evidence of digestive disease. High potency topical steroids (betamethasone 0,5mg/gr twice daily) and 300mg intravenous Infliximab were initiated as the initial line therapy and the ulcers began to heal. We report this case to highlight the presence of cutaneous ulcers without intestinal disease in a young non-pediatric woman as the unique manifestation of the disease.

Triclosan-coated barbed sutures in elective laparoscopic colorectal cancer surgery: a propensity score matched cohort study.

BACKGROUND: Most of the studies published to date which assess the role of antibacterial sutures in surgical site infection (SSI) prevention include heterogeneous groups of patients, and it is therefore difficult to draw conclusions. The objective of the present study was to investigate whether the use of Triclosan-coated barbed sutures (TCBS) was associated with a lower incidence of incisional SSI and lower duration of hospital stay compared to standard sutures, in elective laparoscopic colorectal cancer surgery. METHOD: Observational including patients who underwent elective colorectal cancer laparoscopic surgery between January 2015 and December 2020. The patients were divided into two groups according to the suture used for fascial closure of the extraction incision, TCBS vs conventional non-coated sutures (CNCS), and the rate of SSI was analysed. The TCBS cases were matched to CNCS cases by propensity score matching to obtain comparable groups of patients. RESULTS: 488 patients met the inclusion criteria. After adjusting the patients with the propensity score, two new groups of patients were generated: 143 TCBS cases versus 143 CNCS cases. Overall incisional SSI appeared in 16 (5.6%) of the patients with a significant difference between groups depending on the type of suture used, 9.8% in the group of CNCS and 1.4% in the group of TCBS (OR 0.239 (CI 95%: 0.065-0.880)). Hospital stay was significantly shorter in TCBS group than in CNCS, 5 vs 6 days (p < 0.001). CONCLUSION: TCBS was associated with a lower incidence of incisional SSI compared to standard sutures in a cohort of patients undergoing elective laparoscopic colorectal cancer surgery.

Short-term outcomes of colorectal cancer surgery in older patients: a novel nomogram predicting postoperative morbi-mortality.

PURPOSE: To analyze short-term outcomes of curative-intent cancer surgery in all adult patients diagnosed with colorectal cancer undergoing surgery from January 2010 to December 2019 and determine risk factors for postoperative complications and mortality. METHODS: Retrospective study conducted at a single tertiary university institution. Patients were stratified by age into two groups: < 75 years and ≥ 75 years. Primary outcome was the influence of age on 30-day complications and mortality. Independent risk factors for postoperative adverse events or mortality were analyzed, and two novel nomograms were constructed. RESULTS: Of the 1486 patients included, 580 were older (≥ 75 years). Older subjects presented more comorbidities and tumors were located mainly in right colon (45.7%). After matching, no between-group differences in surgical postoperative complications were observed. The 30-day mortality rate was 5.3% for the older and 0.8% for the non-older group (p < 0.001). In multivariable analysis, the independent risk factors for postoperative complications were peripheral vascular disease, chronic pulmonary disease, severe liver disease, postoperative transfusion, and surgical approach. Independent risk factors for 30-day mortality were age ≥ 80 years, cerebrovascular disease, severe liver disease, and postoperative transfusion. The model was internally and externally validated, showing high accuracy. CONCLUSION: Patients aged ≥ 75 years had similar postoperative complications but higher 30-day mortality than their younger counterparts. Patients with peripheral vascular disease, chronic pulmonary disease, or severe liver disease should be informed of higher postoperative complications. But patients aged ≥ 80 suffering cerebrovascular disease, severe liver disease, or needing postoperative transfusion should be warned of significantly increased risk of postoperative mortality.

Concordance and survival implications of preoperative subclassification of T3 rectal cancers by depth of mesorectal invasion using a 5-mm cut-off point with endorectal ultrasound and magnetic resonance imaging.

Background: Validated rectal cancer staging groups T3 tumours in a single stage and depth of mesorectal invasion subclassification is not standard practice. Our aim is to report concordance between magnetic resonance imaging (MRI) and endorectal ultrasound (ERUS) for preoperative staging of T3 rectal tumours using a 5-mm cut-off point and possible survival implications. Methods: Prospective cohort study including patients staged preoperatively as cT3 by ERUS or magnetic resonance imaging. The maximum depth of penetration beyond the outer longitudinal muscle layer was measured according to a 5-mm cut-off point. Concordance rate and Kappa coefficient were calculated for both techniques. Primary end-points were disease free survival and overall survival (OS) for both groups. Results: A total of 97 patients were included. Disease-free survival in depth of mesorectal invasion ≤5 and >5 mm measured by ERUS was 130.80 (119.20-142.30) vs. 88.38 (56.13-120.64) months (P=0.020), respectively, and 129.90 (117.90-141.90) vs. 93.60 (64.50-122.70) months (P=0.045) when measured by magnetic resonance imaging. Depth of mesorectal invasion ≤5 mm measured by ERUS and MRI was a prognostic factor for both OS [ERUS P=0.009; MRI P=0.019] and DFS (ERUS P=0.026; MRI P=0.054) after Cox regression analysis. Conclusions: T3 subclassification above and below 5mm is feasible by ERUS, shows good concordance with validated magnetic resonance and can easily be incorporated into the diagnostic workup for these patients with possible survival implications.

Sigmoid volvulus: outcomes of treatment and predictors of morbidity and mortality.

PURPOSE: To analyze the treatment outcomes for sigmoid volvulus (SV) and identify risk factors of complications and mortality. METHODS: Observational study of all consecutive adult patients diagnosed with SV who were admitted from January 2000 to December 2020 in a tertiary university institution for conservative management, urgent or elective surgery. Primary outcomes were 30-day postoperative morbidity, mortality and 2-year overall survival (OS), including analysis of risk factors for postoperative morbidity or mortality and prognostic factors for 2-year OS. RESULTS: A total of 92 patients were included. Conservative management was performed in 43 cases (46.7%), 27 patients (29.4%) underwent emergent surgery and 22 (23.9%) were scheduled for elective surgery. Successful decompression was achieved in 87.8% of cases, but the recurrence rate was 47.2%. Mortality rates following episodes were higher for conservative treatment than for urgent or elective surgery (37.2%, 22.2%, 9.1%, respectively; p = 0.044). ASA score > III was an independent risk factor for complications (OR = 5.570, 95% CI = 1.740-17.829, p < 0.001) and mortality (OR = 6.139, 95% CI = 2.629-14.335, p < 0.001) in the 30 days after admission. Patients who underwent elective surgery showed higher 2-year OS than those with conservative treatment (p = 0.011). Elective surgery (HR = 2.604, 95% CI = 1.185-5.714, p = 0.017) and ASA score > III (HR = 0.351, 95% CI = 0.192-0.641, p = 0.001) were independent prognostic factors for 2-year OS. CONCLUSION: Successful endoscopic decompression can be achieved in most SV patients, but with the drawbacks of high recurrence, morbidity and mortality rates. Concurrent severe comorbidities and conservative treatment were independent prognostic factors for morbidity and survival in SV.

LONG-TERM EVOLUTION OF CONTINENCE AND QUALITY OF LIFE AFTER SPHINCTEROPLASTY FOR OBSTETRIC FECAL INCONTINENCE.

PURPOSE: Evaluate the long-term evolution of continence and patient's quality of life after surgical treatment for obstetric fecal incontinence. METHODS: A prospective longitudinal study was conducted including consecutive patients who underwent sphincteroplasty for severe obstetric fecal incontinence. The first phase analyzed changes in continence and impact on quality of life. The second phase studied the long-term evolution reevaluating the same group of patients six years later. Degree of fecal incontinence was calculated using the Cleveland Clinic Score. Quality of life assessment was carried out with the Fecal Incontinence Quality of Life Scale. RESULTS: 35 patients with median age of 55 (range, 28-73) completed the study. Phase One Results: After a postoperative follow-up of 30 months (4-132), Cleveland Clinic Score had improved significantly from a preoperative of 15.7 ± 3.1 to 6.1 ± 5 (p <0.001). Phase Two Results: median follow-up in phase two was 110 months (76- 204). The Cleveland Clinic Score lowered to 8.4 ± 4.9 (p = 0.04). There were no significant differences between phases one and two in terms of quality of life: lifestyle (3.47 ± 0.75 vs. 3.16 ± 1.04), coping/behavior (3.13 ± 0.83 vs 2.80 ± 1.09), depression/self-perception (3.65 ± 0.80 vs 3.32 ± 0.98) and embarrassment (3.32 ± 0.9 vs 3.12 ± 1). CONCLUSION: Sphincteroplasty offers good short-medium term outcomes in continence and quality of life for obstetric fecal incontinence treatment. Functional clinical results deteriorate over time but did not impact on patients' quality of life.

Prognostic implications of surgical specimen quality on the oncological outcomes of open and laparoscopic surgery in mid and low rectal cancer.

PURPOSE: Determine differences in pathologic outcomes between laparoscopic (LAP) and open surgery (OPEN) for mid and low rectal cancer and its influence in long-term oncological outcomes. METHODS: Retrospective case matched study at a tertiary institution. Adults with rectal cancer below 12 cm from the anal verge operated between January 2005 and September 2018 were included. Primary outcomes were quality of specimen, overall survival (OS), disease-free survival (DFS), and local recurrence (LR). RESULTS: The study included 311 patients, LAP = 108 (34.7%), OPEN = 203 (65,3%). A successful resection was accomplished in 81% of the LAP group and in 84.5% of the OPEN (p = 0.505). No differences in free distal margin (LAP = 100%, OPEN = 97.5%; p = 0.156) or circumferential resection margin (LAP = 95.2%, OPEN = 93.2%; p = 0.603) were observed. However, mesorectum quality was incomplete in 16.2% for LAP and in 8.1% for OPEN (p = 0.048). OS was 91.1% for LAP and 81.1% for OPEN (p = 0.360). DFS was 81.4% for LAP and 77.5% for OPEN (p = 0.923). Overall, LR was 2.3% without differences between groups. CONCLUSIONS: Laparoscopic approach could affect the quality of surgical specimen due to technical aspects. However, if principles of surgical oncology are respected, minor pathologic differences in the quality of the mesorectum may not influence on the long-term oncologic outcomes.

Sphincter damage during fistulotomy for perianal fistulae and its relationship with faecal incontinence.

BACKGROUND: The length of sphincter which can be divided during fistulotomy for perianal fistula is unclear. The aim was to quantify sphincter damage during fistulotomy and determine the relationship between such damage with symptoms and severity of faecal incontinence and long-term quality of life (QOL). METHODS: A prospective cohort study was performed over a 2-year period. Patients with intersphincteric and mid to low transsphincteric perianal fistulas without risk factors for faecal incontinence were scheduled for fistulotomy. All patients underwent 3D endoanal ultrasound (3D-EAUS) pre-operatively and 8 weeks postoperatively. Measurements were taken of pre- and postoperative anal sphincter involvement and division. Anal continence was assessed using the Jorge-Wexner scale and QOL scores pre, 6 and 12 months postoperatively. RESULTS: Forty-nine patients were selected. A strong correlation between pre- and postoperative measurements was found p < 0.001. A median length of 41% of the external anal sphincter and 32% of the internal anal sphincter was divided during fistulotomy. Significant differences in mild symptoms of anal continence were found with increasing length of external anal sphincter division. But there was no significant deterioration in continence, soiling, or quality of life scores at the 1-year follow-up. Division of over two-thirds of the external anal sphincter was associated with the highest incontinence rates. CONCLUSIONS: 3D-EAUS is a valuable tool for quantifying the extent of sphincter involvement pre- and postoperatively. Post-fistulotomy faecal incontinence is mild and increases with increasing length of sphincter division but does not affect long-term quality of life.

Rectal advancement flaps for the treatment of transphincteric perianal fistulas: a three-dimensional endoanal ultrasound and quality of life assessment.

This study quantifies the damage to the internal anal sphincter (IAS) after a rectal mucosal advancement flap for a high transphincteric fistula in 16 patients using 3D-endoanal ultrasound. This was correlated with postoperative incontinence and quality of life scores. The median length of involved IAS preoperatively was 50 % (20-100) and 93.72 % for EAS (47.4-100 %). IAS division did not influence continence (p > 0.05). Continence deteriorated between the pre-, postoperative (p = 0.014) and six-month follow-up (p = 0.005), with no significant differences after one year (p > 0.05). The FIQOL score and SF-36 deteriorated initially, with recovery in all domains except for mental health after one year. Three fistulas recurred (18.75 %).

Detection of postoperative plasma circulating tumour DNA and lack of CDX2 expression as markers of recurrence in patients with localised colon cancer.

BACKGROUND: Colon cancer (CC) is a heterogeneous disease. Novel prognostic factors beyond pathological staging are required to accurately identify patients at higher risk of relapse. Integrating these new biological factors, such as plasma circulating tumour DNA (ctDNA), CDX2 staining, inflammation-associated cytokines and transcriptomic consensus molecular subtypes (CMS) classification, into a multimodal approach may improve our accuracy in determining risk of recurrence. METHODS: One hundred and fifty patients consecutively diagnosed with localised CC were prospectively enrolled in our study. ctDNA was tracked to detect minimal residual disease by droplet digital PCR. CDX2 expression was analysed by immunostaining. Plasma levels of cytokines potentially involved in disease progression were measured using ELISAs. A 96 custom gene panel for nCounter assay was used to classify CC into colorectal cancer assigner and CMS. RESULTS: Most patients were classified into CMS4 (37%) and CMS2 (28%), followed by CMS1 (20%) and CMS3 (15%) groups. CDX2-negative tumours were enriched in CMS1 and CMS4 subtypes. In univariable analysis, prognosis was influenced by primary tumour location, stage, vascular and perineural invasion together with high interleukin-6 plasma levels at baseline, tumours belonging to CMS 1 vs CMS2 +CMS3, ctDNA presence in plasma and CDX2 loss. However, only positive ctDNA in plasma samples (HR 13.64; p=0.002) and lack of CDX2 expression (HR 23.12; p=0.001) were found to be independent prognostic factors for disease-free survival in the multivariable model. CONCLUSIONS: ctDNA detection after surgery and lack of CDX2 expression identified patients at very high risk of recurrence in localised CC.

Three-dimensional endoanal ultrasound for diagnosis of perianal fistulas: Reliable and objective technique.

AIM: To evaluate accuracy of three-dimensional endoanal ultrasound (3D-EAUS) as compared to 2D-EAUS and physical examination (PE) in diagnosis of perianal fistulas and correlate with intraoperative findings. METHODS: A prospective observational consecutive study was performed with patients included over a two years period. All patients were studied and operated on by the Colorectal Unit surgeons. The inclusion criteria were patients over 18, diagnosed with a criptoglandular perianal fistula. The PE, 2D-EAUS and 3D-EAUS was performed preoperatively by the same colorectal surgeon at the outpatient clinic prior to surgery and the fistula anatomy was defined and they were classified in intersphincteric, high or low transsphincteric, suprasphincteric and extrasphincteric. Special attention was paid to the presence of a secondary tract, the location of the internal opening (IO) and the site of external opening. The results of these different examinations were compared to the intraoperative findings. Data regarding location of the IO, primary tract, secondary tract, and the presence of abscesses or cavities was analysed. RESULTS: Seventy patients with a mean age of 47 years (range 21-77), 51 male were included. Low transsphincteric fistulas were the most frequent type found (33, 47.1%) followed by high transsphincteric (24, 34.3%) and intersphincteric fistulas (13, 18.6%). There are no significant differences between the number of IO diagnosed by the different techniques employed and surgery (P > 0.05) and, there is a good concordance between intraoperative findings and the 2D-EAUS (k = 0.67) and 3D-EAUS (k = 0.75) for the diagnosis of the primary tract. The ROC curves for the diagnosis of transsphincteric fistulas show that both ultrasound techniques are adequate for the diagnosis of low transsphincteric fistulas, 3D-EAUS is superior for the diagnosis of high transsphincteric fistulas and PE is weak for the diagnosis of both types. CONCLUSION: 3D-EAUS shows a higher accuracy than 2D-EAUS for assessing height of primary tract in transsphincteric fistulas. Both techniques show a good concordance with intraoperative finding for diagnosis of primary tracts.

Sacral nerve stimulation for the treatment of severe faecal incontinence: results after 10 years experience.

INTRODUCTION: The objective of this study is to report our experience with sacral nerve stimulation for the treatment of severe faecal incontinence after the first 10 years with this technique. MATERIAL AND METHODS: Between 2001 and 2011, 49 patients with severe faecal incontinence underwent sacral nerve stimulation. Anorectal manometry, endoanal ultrasound and pudendal nerve latency were performed. Bowel habit diary, severity of faecal incontinence and quality of life scales were evaluated preoperatively and at the end of follow-up. RESULTS: Morbidity occurred in a third of patients, mostly minor. Four definitive devices were explanted. With a median follow-up of 37 months, severity of faecal incontinence, urge and incontinence episodes significantly improved at the end of follow-up. Patients' subgroup with major follow-up of 5 years significantly improved the severity of faecal incontinence but not the parameters of the bowel habit diary. Quality of life showed no significant improvement. Descriptive data in patients with sphincter defects did not show worse results than with sphincter integrity. CONCLUSION: Sacral nerve stimulation is a safe technique for severe faecal incontinence with good functional medium-term results. In the long term, severity of the faecal incontinence also improves but studies with larger sample are necessary to show if other clinical parameters and the quality of life support this information. Preliminary results in patients with sphincter defects suggest that this technique could be effective in this group but future studies will have to confirm these findings.

Factors associated with health-related quality of life in a cohort of Spanish breast cancer patients.

BACKGROUND: Several factors can modify health-related quality of life (HRQOL) of breast cancer survivors. The objective of the current study was to analyse the associations between HRQOL scores 1 year after breast cancer surgery and sociodemographic and clinical factors. METHODS: This was an observational, multicentre and prospective study of a cohort of patients who underwent oncological breast cancer surgery and which was followed up for 1 year. The HRQOL was assessed at 1 year after surgery using three questionnaires: EuroQol-5D, EORTC QLQ-C30 and its breast-specific module BR-23. RESULTS: A total of 364 patients participated in the study. Some factors were associated with better HRQOL 1 year after surgery: age between 60 and 69 years and under 50 years, being single or a housewife, stage I-II, invasive papillary carcinoma, breast-conserving surgery (BCS) or lack of axillary dissection. However, only the following were independent predictive factors: being single or a housewife, BCS, invasive papillary carcinoma, coming from an outpatient clinic or not receiving radiotherapy. Further, some factors were independent predictors of a worse HRQOL: age over 70 years, being married, separated or widowed, stage III or not receiving adjuvant chemotherapy. CONCLUSIONS: Demographic and clinical factors can influence HRQOL, some of them independently.