Background
Rectal cancer is frequent in Germany and worldwide. Several studies have assessed laparoscopic surgery as a treatment option and most have shown favorable results. However, long-term ...oncologic safety remains a controversial issue.
Methods
The current dataset derives from 30 clinical cancer registries in Germany and includes 16,378 patients diagnosed with rectal cancer between 2007 and 2016. Outcomes were 90-day mortality, overall survival (OS), local recurrence-free survival (RFS) and relative survival of patients treated with either open or laparoscopic surgery. Multivariable logistic regression was used to evaluate factors that affected the probability of a patient undergoing laparoscopic surgery as well as to evaluate short-term mortality. OS and RFS were analyzed by Kaplan–Meier plots and multivariable Cox regression conducted separately for UICC stages I–III, tumor location, and sex as well as by propensity score matching followed by univariable and multivariable survival analysis.
Results
Of 16,378 patients, 4540 (27.7%) underwent laparoscopic surgery, a trend which increased during the observation period. Patients undergoing laparoscopy attained better results for 90-day mortality (odds ratio, OR 0.658, 95% confidence interval, CI 0.526–0.822). The 5-year OS rate in the laparoscopic group was 82.6%, vs. 76.6% in the open surgery group, with a hazard ratio (HR) of 0.819 in multivariable Cox regression (95% CI 0.747–0.899,
p
< 0.001). The laparoscopic group showed a better 5-year RFS, with 81.8 vs. 74.3% and HR 0.770 (95% CI 0.705–0.842,
p
< 0.001). The 5-year relative survival rates were also in favor of laparoscopy, with 93.1 vs. 88.4% (
p
= 0.012).
Conclusion
Laparoscopic surgery for rectal cancer can be performed safely and, according to this study, is associated with an oncological outcome superior to that of the open procedure. Therefore, in the absence of individual contraindications, it should be considered as a standard approach.
Summary Background Laparoscopic surgery as an alternative to open surgery in patients with rectal cancer has not yet been shown to be oncologically safe. The aim in the COlorectal cancer Laparoscopic ...or Open Resection (COLOR II) trial was to compare laparoscopic and open surgery in patients with rectal cancer. Methods A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries. Patients (aged ≥18 years) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were randomly assigned to either laparoscopic or open surgery in a 2:1 ratio, stratified by centre, location of tumour, and preoperative radiotherapy. The study was not masked. Secondary (short-term) outcomes—including operative findings, complications, mortality, and results at pathological examination—are reported here. Analysis was by modified intention to treat, excluding those patients with post-randomisation exclusion criteria and for whom data were not available. This study is registered with ClinicalTrials.gov , number NCT00297791. Findings The study was undertaken between Jan 20, 2004, and May 4, 2010. 1103 patients were randomly assigned to the laparoscopic (n=739) and open surgery groups (n=364), and 1044 were eligible for analyses (699 and 345, respectively). Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group (median 200 mL IQR 100–400 vs 400 mL 200–700, p<0·0001); however, laparoscopic procedures took longer (240 min 184–300 vs 188 min 150–240; p<0·0001). In the laparoscopic surgery group, bowel function returned sooner (2·0 days 1·0–3·0 vs 3·0 days 2·0–4·0; p<0·0001) and hospital stay was shorter (8·0 days 6·0–13·0 vs 9·0 days 7·0–14·0; p=0·036). Macroscopically, completeness of the resection was not different between groups (589 88% of 666 vs 303 92% of 331; p=0·250). Positive circumferential resection margin (<2 mm) was noted in 56 (10%) of 588 patients in the laparoscopic surgery group and 30 (10%) of 300 in the open surgery group (p=0·850). Median tumour distance to distal resection margin did not differ significantly between the groups (3·0 cm IQR 2·0–4·8 vs 3·0 cm 1·8–5·0, respectively; p=0·676). In the laparoscopic and open surgery groups, morbidity (278 40% of 697 vs 128 37% of 345, respectively; p=0·424) and mortality (eight 1% of 699 vs six 2% of 345, respectively; p=0·409) within 28 days after surgery were similar. Interpretation In selected patients with rectal cancer treated by skilled surgeons, laparoscopic surgery resulted in similar safety, resection margins, and completeness of resection to that of open surgery, and recovery was improved after laparoscopic surgery. Results for the primary endpoint—locoregional recurrence—are expected by the end of 2013. Funding Ethicon Endo-Surgery Europe, Swedish Cancer Foundation, West Gothia Region, Sahlgrenska University Hospital.
Background
Since 2010, laparoscopic transanal total mesorectal excision (TaTME) has been increasingly used for low and very low rectal cancer. It is supposed to improve visibility and access to the ...dissection planes in the pelvis. This study reports on short- and long-term outcomes of the first 100 consecutive patients treated with TaTME in a certified German colorectal cancer center.
Patients and methods
Data were derived from digital patient files and official cancer registry reports for patients with TaTME tumor surgery between July 2014 and January 2020. The primary outcome was the 3-year local recurrence rate and local recurrence-free survival (LRFS). Secondary endpoints included overall survival (OAS), disease-free survival (DFS), operation time, completeness of local tumor resection, lymph node resection, and postoperative complications. The Kaplan–Meier method was employed for the survival analyses; competing risks were considered in the time-to-event analysis.
Results
During the observation period, the average annual operation time decreased from 272 to 178 min. Complete local tumor resection was achieved in 97% of the procedures. Major postoperative complications (Clavien–Dindo 3–4) occurred in 11% of the cases. At a median follow-up time of 2.7 years, three patients had suffered from a local recurrence. Considering competing risks, this corresponds to a 3-year cumulative incidence rate for local recurrence of 2.2% and a 3-year LRFS of 81.9%. 3-year OAS was 82.9%, and 3-year DFS was 75.7%.
Conclusion
TaTME is associated with favorable short and long-term outcomes. Since it is technically demanding, structured training programs and more research on the topic are indispensable.
The aim of this study was to evaluate oncological outcome for patients with and without anastomotic leakage after colon or rectal cancer surgery.
The role of anastomotic leakage in oncological ...outcome after colorectal cancer surgery is still topic of debate and impact on follow-up and consideration for further treatment remains unclear.
Patients included in the international, multicenter, non-inferior, open label, randomized, controlled trials COLOR and COLOR II, comparing laparoscopic surgery for curable colon (COLOR) and rectal (COLOR II) cancer with open surgery, were analyzed. Patients operated by abdominoperineal excision were excluded. Both univariate and multivariate analyses were performed to investigate the impact of leakage on overall survival, disease-free survival, local and distant recurrences, adjusted for possible confounders. Primary endpoints in the COLOR and COLOR II trial were disease-free survival and local recurrence at 3-year follow-up, respectively, and secondary endpoints included anastomotic leakage rate.
For colon cancer, anastomotic leakage was not associated with increased percentage of local recurrence or decreased disease-free-survival. For rectal cancer, an increase of local recurrences (13.3% vs 4.6%; hazard ratio 2.96; 95% confidence interval 1.38-6.34; P = 0.005) and a decrease of disease-free survival (53.6% vs 70.9%; hazard ratio 1.67; 95% confidence interval 1.16-2.41; P = 0.006) at 5-year follow-up were found in patients with anastomotic leakage.
Short-term morbidity, mortality, and long-term oncological outcomes are negatively influenced by the occurrence of anastomotic leakage after rectal cancer surgery. For colon cancer, no significant effect was observed; however, due to low power, no conclusions on the influence of anastomotic leakage on outcomes after colon surgery could be reached. Clinical awareness of increased risk of local recurrence after anastomotic leakage throughout the follow-up is mandatory.Trial Registration: Registered with ClinicalTrials.gov, number NCT00387842 and NCT00297791.
The pathogenesis of fistulae in Crohn's disease (CD) patients is barely understood. We recently showed that more than two-thirds of CD fistulae are covered with flat, mesenchymal-like cells ...(transitional cells TC) forming a patchy basement membrane. Epithelial-to-mesenchymal transition (EMT) is a process of reprogramming epithelial cells, allowing them to migrate more effectively and giving epithelial cells an "invasive" potential. EMT has been suggested to be crucial in fibrosis found in different tissues and diseases. We therefore investigated whether EMT could be involved in the pathogenesis of fistulae formation in CD.
In all, 18 perianal fistulae, 2 enteroenteric, and 1 enterovesical fistulae from 17 CD patients were analyzed. In addition 2 perianal fistulae of non-CD patients were studied. Hematoxylin and eosin staining, immunohistochemistry for the expression of cytokeratins 8 and 20, beta6-integrin, E-cadherin, beta-catenin, vimentin, and TGF-beta1 and 2 were performed according to standard techniques.
The TC covering perianal or enteroenteric fistulae were strongly positive for cytokeratins 8 and 20 but negative for vimentin, indicating their epithelial origin. beta6-Integrin and TGF-beta had the highest staining intensities in the transitional zone between the epithelium and the TC. Expression of junctional proteins such as E-cadherin was reduced in TC as compared to regular fistulae epithelium. In addition, a translocation of beta-catenin from the membrane to the cytoplasm was observed.
Our data for the first time indicate an expression pattern of epithelial and mesenchymal markers in TC associated with fistulae formation that is characteristic for EMT. Studying the pathways of EMT during intestinal fistulae formation may help to develop new therapeutic strategies.
Colorectal cancer (CRC) is the third most common cancer worldwide. The main treatment options are laparoscopic (LS) and open surgery (OS), which might differ in their impact on the cellular immunity ...so indispensable for anti-infectious and antitumor defense. MEDLINE, Embase, Web of Science (SCI-EXPANDED), the Cochrane Library, Google Scholar, ClinicalTrials.gov, and ICTRP (WHO) were systematically searched for randomized controlled trials (RCTs) comparing cellular immunity in CRC patients of any stage between minimally invasive and open surgical resections. A random effects-weighted inverse variance meta-analysis was performed for cell counts of natural killer (NK) cells, white blood cells (WBCs), lymphocytes, CD4+ T cells, and the CD4+/CD8+ ratio. The RoB2 tool was used to assess the risk of bias. The meta-analysis was prospectively registered in PROSPERO (CRD42021264324). A total of 14 trials including 974 participants were assessed. The LS groups showed more favorable outcomes in eight trials, with lower inflammation and less immunosuppression as indicated by higher innate and adaptive cell counts, higher NK cell activity, and higher HLA-DR expression rates compared to OS, with only one study reporting lower WBCs after OS. The meta-analysis yielded significantly higher NK cell counts at postoperative day (POD)4 (weighted mean difference (WMD) 30.80 cells/µL 19.68; 41.92,
0.00001) and POD6-8 (WMD 45.08 cells/µL 35.95; 54.21,
0.00001). Although further research is required, LS is possibly associated with less suppression of cellular immunity and lower inflammation, indicating better preservation of cellular immunity.
With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from ...younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age. The heterogeneity of this group, combined with the limited available data, impedes drafting evidence-based guidelines. Therefore, a multidisciplinary task force convened experts from the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology and the American College Surgeons Commission on Cancer, with the goal of identifying the best practice to promote personalized rectal cancer care in older patients.
A crucial element for personalized care was recognized as the routine screening for frailty and geriatrician involvement and personalized care for frail patients. Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes. Therefore, properly selected patients should be considered for surgical resection. Local excision can be utilized when balancing oncologic outcomes, frailty and life expectancy. Watch and wait protocols, in expert hands, are valuable for selected patients and adjuncts can be added to improve complete response rates. Functional recovery and patient-reported outcomes are as important as oncologic-specific outcomes in this age group. The above recommendations and others were made based on the best-available evidence to guide the personalized treatment of elderly patients with rectal cancer.
Background
Internal rectal prolapse and rectocele are frequent clinical findings in patients with obstructed defecation syndrome (ODS). However, there is still no evidence whether stapled transanal ...rectal resection (STARR) provides a safe and effective surgical option. Therefore, the German STARR registry was initiated to assess safety, effectiveness, and quality of life.
Methods
The German STARR registry was designed as an interventional, prospective, multicenter audit. Primary outcomes include safety (morbidity and adverse events), effectiveness (ODS, symptom severity, and incontinence scores), and quality of life (PAC-QoL and EQ-5D) documented at baseline and at 6 and 12 months. Statistical evaluation was performed by an independent research organization of clinical epidemiology.
Results
Complete data of 379 patients (78% females, mean age 57.8 years) were entered into the registry database. Mean operative time was 40 min, mean hospitalization was 5.5 days. A total of 103 complications and adverse events were reported in 80 patients (21.1%) including staple line complications (minor bleeding, infection, or partial dehiscence; 7.1%), major bleeding (2.9%), and postsurgical stenosis (2.1%). Comparisons of ODS and symptom severity scores (SSS) demonstrated a significant reduction in ODS score between baseline (mean 11.14) and 6 months (mean 6.43), which was maintained at 12 months (mean 6.45), and SSS at preoperative and at 6- and 12-month follow-up (13.02 vs. 7.34 vs. 6.59; paired
t
test,
p
< 0.001). Significant reduction in ODS symptoms was matched by an improvement in quality of life as judged by symptom-specific PAC-QoL and generic ED-5Q (utility and visual analog scale) scores and was not associated with an impairment of incontinence score following STARR (
p
> 0.05). However, 11 patients (2.9%) showed de novo incontinence, and new-onset symptoms of fecal urgency were observed in 25.3% of patients.
Conclusion
These data indicate that STARR is a safe and effective procedure. However, conclusions are limited due to the selection and reporting bias of a registry. The problem of fecal urgency needs cautious reassessment.
Background
Intestinal fibrosis and subsequent stricture formation represent frequent complications of Crohn’s disease (CD). In many organs, fibrosis develops as a result of epithelial to mesenchymal ...transition (EMT). Recent studies suggested that EMT could be involved in intestinal fibrosis as a result of chronic inflammation. Here, we investigated whether EMT might be involved in stricture formation in CD patients.
Methods
Human colonic tissue specimens from fibrotic areas of 18 CD and 10 non-IBD control patients were studied. Immunohistochemical staining of CD68 (marker for monocytes/macrophages), transforming growth factor-β
1
(TGFβ
1
), β-catenin, SLUG, E-.cadherin, α-smooth muscle actin and fibroblast activation protein (FAP) were performed using standard techniques.
Results
In fibrotic areas in the intestine of CD patients, a large number of CD68-positive mononuclear cells was detectable suggesting an inflammatory character of the fibrosis. We found stronger expression of TGFβ
1
, the most powerful driving force for EMT, in and around the fibrotic lesions of CD patients than in non-IBD control patients. In CD patients membrane staining of β-catenin was generally weaker than in control patients and more cells featured nuclear staining indicating transcriptionally active β-catenin, in fibrotic areas. In these regions we also detected nuclear localisation of the transcription factor, SLUG, which has also been implicated in EMT pathogenesis. Adjacent to the fibrotic tissue regions, we observed high levels of FAP, a marker of reactive fibroblasts.
Conclusions
We demonstrate the presence of EMT-associated molecules in fibrotic lesions of CD patients. These findings support the hypothesis that EMT might play a role for the development of CD-associated intestinal fibrosis.
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