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Background and aims:
In a randomized trial the effect of short-term preoperative radiotherapy and postoperative chemotherapy was studied in patients undergoing total mesorectal excision (TME) for clinically resectable rectal cancer. The primary endpoint was overall survival. The secondary endpoints published herein were the incidence of postoperat...
Contexts in source publication
Context 1
... of these eight deaths were caused by anastomotic leakage, two in each group. Three patients died of acute myocardial ischemia and one of mechanical ileus (Table 3). ...
Context 2
... incidence of anastomotic leakage was 20.6% in the surgery group and 27.4% in the RT+CT group (p =0.305, Table 3). These figures include both clinical leakages (n =33) and sinuses detected in routine sig-moidoscopy 6 weeks after surgery (n =11). ...
Citations
... Another prospective study reported that short-course radiotherapy had a higher rate of AL than surgery alone (27.4% vs. 20.6%), but the results were not significantly different [68]. ...
Objective:
Neoadjuvant radiotherapy (nRT) is an important treatment approach for rectal cancer. The relationship, however, between nRT and postoperative complications is still controversial. Here, we conducted a meta-analysis to evaluate such concerns.
Methods:
The electronic literature from 1983 to 2021 was searched in PubMed, Embase, and Web of Science. Postoperative complications after nRT were included in the meta-analysis. The pooled odds ratio (OR) was calculated by the random-effects model. Statistical analysis was conducted by Review Manager 5.3 and STATA 14.
Results:
A total of 23,723 patients from 49 studies were included in the meta-analysis. The pooled results showed that nRT increased the risk of anastomotic leakage (AL) compared to upfront surgery (OR = 1.23; 95% CI, 1.07-1.41; p=0.004). Subgroup analysis suggested that both long-course (OR = 1.20, 95% CI 1.03-1.40; p=0.02) and short-course radiotherapy (OR = 1.25, 95% CI, 1.02-1.53; p=0.04) increased the incidence of AL. In addition, nRT was the main risk factor for wound infection and pelvic abscess. The pooled data in randomized controlled trials, however, indicated that nRT was not associated with AL (OR = 1.01; 95% CI 0.82-1.26; p=0.91).
Conclusions:
nRT may increase the risk of AL, wound infection, and pelvic abscess compared to upfront surgery among patients with rectal cancer.
... Randomized controlled studies from Sebag-Montefiore (20) suggested that neoadjuvant chemoradiation did not increase the incidence of anastomotic leakage. Salmenkylä et al. (21) also showed that the anastomotic leakage rate did not significantly differ between the surgery and radiochemotherapy groups (20.6% vs. 27.4%). In this study, neoadjuvant chemoradiation did not show a significant increase in the risk of complications and leakage. ...
Objective
To investigate the risk factors for postoperative complications and anastomotic leakage after robotic surgery for mid and low rectal cancer and their influence on long-term outcomes.
Methods
A total of 641 patients who underwent radical mid and low rectal cancer robotic surgery at Zhongshan Hospital Fudan University from January 2014 to December 2018 were enrolled in this study. The clinicopathological factors of the patients were collected. The risk factors for short-term outcomes of complications and anastomotic leakage were analyzed, and their influences on recurrence and overall survival were studied.
Results
Of the 641 patients, 516 (80.5%) underwent AR or LAR procedures, while 125 (19.5%) underwent the NOSES procedure. Only fifteen (2.3%) patients had stoma diversion. One hundred and seventeen patients (17.6%) experienced surgical complications. Anastomotic leakage occurred in 44 patients (6.9%). Eleven patients (1.7%) underwent reoperation within 90 days after surgery. Preoperative radiotherapy did not significantly increase anastomotic leakage in our study (7.4% vs. 6.8%, P = 0.869). The mean postoperative hospital stay was much longer with complication (10.4 vs. 7.1 days, P<0.05) and leakage (12.9 vs. 7.4 days, P < 0.05). Multivariate analysis showed that male sex (OR = 1.855, 95% CI: 1.175–2.923, P < 0.05), tumor distance 5 cm from the anus (OR = 1.563, 95% CI: 1.016–2.404, P < 0.05), and operation time length (OR = 1.563, 95% CI: 1.009–2.421, P < 0.05) were independent risk factors for complications in mid and low rectal cancer patients. The same results for anastomotic leakage: male sex (OR = 2.247, 95% CI: 1.126–4.902, P < 0.05), tumor distance 5 cm from the anus (OR = 2.242, 95% CI: 1.197–4.202, P < 0.05), and operation time length (OR = 2.114, 95% CI: 1.127–3.968, P < 0.05). The 3-year DFS and OS were 82.4% and 92.6% with complication, 88.4% and 94.0% without complication, 88.6% and 93.1% with leakage, and 87.0% and 93.8% without leakage, respectively. The complication and anastomotic leakage showed no significant influences on long-term outcomes.
Conclusion
Being male, having a lower tumor location, and having a prolonged operation time were independent risk factors for complications and anastomotic leakage in mid and low rectal cancer. Complications and anastomotic leakage might have no long-term impact on oncological outcomes for mid and low rectal cancer with robotic surgery.
... Treatment toxicity of intensified chemotherapeutic protocols is of high patient relevance and is of utmost importance for the assessment of comprehensive applicability of such protocols. Furthermore, it has been shown that neoadjuvant treatment has a direct influence on postoperative morbidity and complications such as anastomotic leakage [42,43]. Therefore, these endpoints have to be evaluated in an attempt to appraise the different treatment concepts comprehensively. ...
Background:
Neoadjuvant (chemo-)radiation has proven to improve local control compared to surgery alone, but this improvement did not translate into better overall or disease-specific survival. The addition of oxaliplatin to fluoropyrimidine-based neoadjuvant chemoradiotherapy holds the potential of positively affecting survival in this context since it has been proven effective in the palliative and adjuvant setting of colorectal cancer. Thus, the objective of this systematic review is to assess the efficacy, safety, and quality of life resulting from adding a platinum derivative to neoadjuvant single-agent fluoropyrimidine-based chemoradiotherapy in patients with Union for International Cancer Control stage II and III rectal cancer.
Methods:
MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials will be systematically searched to identify all randomized controlled trials comparing single-agent fluoropyrimidine-based chemoradiotherapy to combined neoadjuvant therapy including a platinum derivative. Predefined data on trial design, quality, patient characteristics, and endpoints will be extracted. Quality of included trials will be assessed according to the Cochrane Risk of Bias Tool, and the GRADE recommendations will be applied to judge the quality of the resulting evidence. The main outcome parameter will be survival, but also treatment toxicity, perioperative morbidity, and quality of life will be assessed.
Discussion:
The findings of this systematic review and meta-analysis will provide novel insights into the efficacy and safety of combined neoadjuvant chemoradiotherapy including a platinum derivative and may form a basis for future clinical decision-making, guideline evaluation, and research prioritization.
Systematic review registration:
PROSPERO CRD42017073064.
... 18,19 In addition, chemotherapy may concomitantly damage adjacent organs or tissues, and these adverse effects are difficult to avoid. 20,21 In recent decades, the development of nanotechnology has provided an opportunity to overcome the aforementioned side effects. The integration of various nanomaterials (NMs) with spectroscopic, biochemical, and optical methods has allowed the development of advanced methods for tumor therapy, which may revolutionize the treatment of tumors. ...
Tumors are one of the most serious human diseases and cause numerous global deaths per year. In spite of many strategies applied in tumor therapy, such as radiation therapy, chemotherapy, surgery, and a combination of these treatments, tumors are still the foremost killer worldwide among human diseases, due to their specific limitations, such as multidrug resistance and side effects. Therefore, it is urgent and necessary to develop new strategies for tumor therapy. Recently, the fast development of nanoscience has paved the way for designing new strategies to treat tumors. Nanomaterials have shown great potential in tumor therapy, due to their unique properties, including passive targeting, hyperthermia effects, and tumor-specific inhibition. This review summarizes the recent progress using the innate antitumor properties of metallic and nonmetallic nanomaterials to treat tumors, and related challenges and prospects are discussed.
... Because of its poor prognosis and its high local recurrence rate, neoadjuvant therapy with radiation and/or chemotherapy is often used in advanced rectal tumor and has become a standard of care in many centers. [2,3] Anastomotic leakage (AL) is the most important surgical complication with a high risk of pelvic sepsis. [4] Besides being life threatening, this might lead to impaired functional results on the long term. ...
... Our rate is evaluated as high: logistic regression revealed that the probability of AL increases with neoadjuvant treatment (34.7% of the patients with versus 66.3% of the patients without preoperative treatment). Salmenkyl€ a et al. [3] did not report a statistically significant difference between irradiated and non-irradiated patients (27.4 versus 20.6% respectively). Beirens and Penninckx [13] reported from the PROCARE-Belgium study an overall rate of AL of 6.5% with a wide variation between 0% and 25%. ...
Background: Rectal adenocarcinomas surgery morbidity and mortality might be impaired by neoadjuvant therapy. We performed this retropsective study to be compared with the PROCARE study running afterwards.
Methods: We performed a retrospective study of 95 patients operated on for rectal adenocarcinoma in a single institution during the period of 2007–2009. We used logistic regression to estimate the relationship between possible predictive parameters of anastomotic leakage (AL).
Results: The laparoscopic approach is favored in 63.1% of the cases with a conversion rate of 11.6%, mainly in man (6 out of 7). For low rectal cancer though, laparotomy was the first choice (92.3%). From a carcinological point of view, laparoscopy allowed a complete tumor resection according to the PME (n = 27) and TME (n = 26) standards. Multivariate analysis revealed that women, lower BMI, lower rectum tumor, laparoscopic surgery, neoadjuvant treatment and anal suture were associated with higher risk of AL. The mean hospital stay was 15.4 days (3–46 days) with an in-hospital mortality rate of 3.1%. Adjuvant chemotherapy was completed in 42.1% of the patients. Despite these treatments, we registered a recurrence rate of 26.6%. Of these, 72% were distally localized and 12% exclusively locally. Among the patients operated on by laparoscopy, there was one local recurrence and one local with distant metastases (3.7%). The one- and three-year survival rates were 91.5% and 80.4%, respectively.
Conclusions: Our study showed a higher rate of AL than expected (18%). In our series recorded in PROCARE-Home, our leak rate has dropped to 10%. It may be indicating a positive effect of PROCARE.
... Thus, the side-effects are difficult to avoid, chemotherapy often resulting in damage to other organs and tissues not affected by neoplastic disease. Due to concomitant damage to adjacent tissues, radiotherapy is also associated with significant side-effects (Bruheim et al., 2010;Salmenkylä et al., 2012). ...
Colorectal cancer is a major public health issue, being the third most common cancer in men and the second in women. It is one of the leading causes of cancer deaths. Nanomedicine is an emerging field of interest, many of its aspects being linked to cancer research. Chemotherapy has a well-established role in colorectal cancer management, unfortunately being limited by inability to have a selective distribution, by multidrug resistance and adverse effects. Researches carried out in recent years about nanotechnologies aimed, among others, to resolve the issues mentioned above. Targeted and localized delivery of the chemotherapeutic drugs, using nanoparticles, with selective destruction of cancerous cells would minimize the toxicity on healthy tissues. Also, the use of nanomaterials as contrast agent could improve sensitivity and specificity of diagnosis. The purpose of this review is to highlight the recent achievements of cancer research by use of nanomaterials, in the idea of finding the ideal composite, capable to simultaneous diagnostic and treat cancer.
... The influence of (chemo)radiation on anastomotic leakage has also been studied in other solid tumors like rectal cancer. A large randomized and a large retrospective study showed that neo-adjuvant chemoradiation did not influence anastomotic leakage rates following Total Mesorectal Excision in patients with rectal cancer [31,32]. Another large Dutch Multicentre RCT showed no difference in anastomotic leakage rates between patients who received short course neoadjuvant radiotherapy followed by surgery compared to surgery alone. ...
Neoadjuvant chemoradiation might increase anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. The aim of this study was to determine the influence of radiation dose on the incidence of leakage and stenosis.
Fifty-three patients with esophageal cancer received neoadjuvant chemoradiation (23 × 1.8 Gy) (combined with Paclitaxel and Carboplatin) followed by a transhiatal esophagectomy between 2009 and 2011. On planning CT, the future anastomotic region was determined and the mean radiation dose, V20, V25, V30, V35 and V40 were calculated. Logistic regression analysis was conducted to examine determinants of anastomotic leakage and stenosis.
Anastomotic leaks occurred in 13 of 53 patients (25.5%) and anastomotic stenosis occurred in 24 of 53 patients (45.3%). Median follow-up was 20 months. Logistic regression analysis showed that mean dose, V20-V40, age, co-morbidity, method of anastomosis, operating time and interval between last radiotherapy treatment and surgery were not predictors of anastomotic leakage and stenosis.
A radiation dose of 23 × 1.8 Gy on the future anastomotic region has no influence on the occurrence of anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by transhiatal esophagectomy.
... multicenter cohort studies from spain and the united kingdom report an hP rate of ≈10%, whereas the hP rates in the swedish and Dutch population are 15% and 24%. [6][7][8][9] in contrast, hP consisted of only a small percent in european RCts, [10][11][12] and several other large RCts did not even mention hP as a distinct surgical procedure. [13][14][15] there are no literature data about the impact of Rt on postoperative outcome after hP, except for 1 cohort study in which a trend toward a higher rate of pelvic sepsis was found after Rt. 16 therefore, the purpose of this study was to evaluate the impact of Rt on the risk of postoperative abscess formation requiring reintervention during initial admission and other short-term postoperative outcomes after hP using a national audit database. ...
Background:
The effects of neoadjuvant radiotherapy on healing of the rectal stump after a Hartmann procedure for rectal cancer are unknown.
Objective:
The purpose of this study was to analyze the impact of radiotherapy on postoperative complications after a Hartmann procedure for rectal cancer at a population level.
Design:
This was a population-based observational study. Postoperative outcomes were compared between Hartmann procedures with and without radiotherapy. Risk factors for postoperative intra-abdominal abscess requiring reintervention, any reintervention, and 30-day or in-hospital mortality were analyzed using a multivariable model.
Settings:
The study included in-hospital registration for the Dutch Surgical Colorectal Audit.
Patients:
Patients with rectal cancer who underwent a Hartmann procedure (total or partial mesorectal excision with end colostomy) between 2009 and 2013 were included.
Main outcome measures:
Abdominal abscess requiring reintervention, any reintervention, and 30-day or in-hospital mortality were measured.
Results:
Of 1728 patients who underwent a Hartmann procedure for rectal cancer, 90.5% (n = 1563) received preoperative radiotherapy. Intra-abdominal abscess formation was significantly increased after radiotherapy (7.0% vs 3.0%; p = 0.049). Overall reinterventions (15.2% vs 15.4%; p = 0.90) and 30-day mortality (2.4% vs 3.5%; p = 0.48) were not associated with radiotherapy in univariable analysis. In multivariable analysis, radiotherapy was an independent predictor of postoperative intra-abdominal abscess requiring reintervention (OR, 2.81 (95% CI, 1.01-7.78)) but was not associated with overall reinterventions or mortality.
Limitations:
This study was limited by the data being self-reported. Case-mix adjustment was limited to information available in the data set, and no long-term outcome data were available.
Conclusions:
Based on these population-based data, radiotherapy is independently associated with an increased risk of postoperative intra-abdominal abscess requiring reintervention after Hartmann procedure for rectal cancer. This finding is relevant for patient-tailored postoperative care but should probably not influence indication for radiotherapy, because it did not affect overall reinterventions and mortality (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A193).
... 4 Among these, we consider as important the advantage of avoiding the delay in starting chemotherapy, which can be seen in case of septic pelvic complications (i.e., anastomotic leakage), which occurs in between 12 and 27.4 % of patients after rectal resection. [22][23][24] Such a delay could have terrible prognostic consequences in a group of patients threatened by the progression of the liver metastases beyond all possibility of cure. ...
Background:
The treatment of patients with metastatic rectal cancer remains controversial. We developed a reverse strategy, the liver-first approach, to optimize the chance of a curative resection. The aim of this study was to assess rectal outcomes after reverse treatment of patients with metastatic rectal cancer.
Methods:
From May 2000 to November 2013, a total of 34 consecutive selected patients with histology-proven adenocarcinoma of the rectum and liver metastases were prospectively entered into a dedicated computerized database. All patients were treated via our reverse strategy. Rectal and overall survival outcomes were analyzed.
Results:
Most patients presented with advanced disease (median Fong clinical risk score of 3; range 2-5). One patient failed to complete the whole treatment (3%). Rectal surgery was performed after a median of 3.9 months (range 0.4-17.8 months). A total of 73.3% patients received preoperative radiotherapy. Perioperative mortality and morbidity rates were 0 and 27.3% after rectal surgery. Severe complications were reported in two patients (6.1%): one anastomotic leak and one systemic inflammatory response syndrome. The median hospital stay was 11 days (range 5-23 days). Complete local pathological response was observed in three patients (9.1%). The median number of lymph nodes collected was 14. The R0 rate was 93.9%. There was no positive circumferential margin. After a mean follow-up of 36 months after rectal surgery, 5-year overall survival was 52.5%. Five patients experienced pelvic recurrence.
Conclusions:
In our cohort of selected patients with stage IV rectal cancer, the reverse strategy was not only safe and effective, but also oncologically promising, with a low morbidity rate and high long-term survival.
... One of the main disadvantages of RT is the large number of severe adverse events, which may occur many years after the procedure. Wound infections and perineal wound dehiscence are more common in irradiated patients (12), as well as skin reaction (with an incidence of up to 86.7%), radiation cystitis (34.6%), proctitis (89.2%) and enteritis (33.6%) (13). The development of nonantibiotic-associated pseudomembranous colitis, caused by Clostridium difficile, which represent nowa-days a serious public health problem in hospitalized patients, has also been diagnosed (14). ...
Preoperative radiotherapy in the treatment of rectal cancer wasthought to be an achievement of similar importance to totalmesorectal excision (TME), for the therapeutic management ofrectal malignancies. However, numerous criticisms have beendiscussed in this field lately. We have analysed the two mainpurposes of preoperative radiation: possible sphincter preservationand the conversion of a non-resectable tumor into aresectable one in a series of 31 consecutive patients, operatedin our clinic. In 20 of them, preoperative radio chemoradiotherapywas applied, while 11 patients were firstly operated andthen irradiated. The surgical procedure included total mesorectalexcision in 30 patients, as part of a low anterior resection,in 13 cases and of an abdominal perineal resection, inthe other 17 cases. We have found that preoperative radiotherapyimproves the local recurrence rate but has no influenceon the overall survival rate. However, we should not overlookthe adverse effects of this method: toxicity of radiotherapy onthe small bowel and the urinary bladder, the healing of theperineal wounds and the risk of anastomotic leaks. Weconcluded in favor of elective preoperative radiotherapy inselected cases: any T4 tumors, T3 tumors which threaten themesorectal fascia on MRI, whenever there is a suspicion ofnodal involvement and also for very low tumors.
