Primary Rectal Cancer Research Articles

The awareness of radiologists for the presence of lateral lymph nodes in patients with locally advanced rectal cancer: a single-centre, retrospective cohort study

ObjectivesEnlarged lateral lymph nodes (LLNs) are associated with increased (lateral) local recurrence rates. Size and anatomical location should therefore always be reported by radiologists and discussed during multidisciplinary meetings. The objective was to investigate how often LLNs are mentioned in MRI reports in a tertiary referral centre.MethodsA single - centre, retrospective study of 202 patients treated for primary rectal cancer between 2012 and 2020, with at least a T2 tumour located within 12cm of the anorectal junction. The radiology reports were written by 30–40 consultant radiologists. MRI scans were independently re-assessed by an expert radiologist. The primary outcome was how often the presence or absence of LLNs was mentioned in the initial report.ResultsPrimary MRI reports explicitly mentioned the presence or absence of LLNs in 89 (44%) cases. Of the 43 reports with present LLNs, only one (1%) reported on all features such as size, location or malignant features. Expert review revealed 17 LLNs which were ≥ 7 mm (short-axis); two of these were not mentioned in the original reports. In 14/43 (33%) cases, LLNs were discussed during the primary multidisciplinary meeting, while 17/43 (40%) restaging MRI reports failed to report on the previously visible LLN. Reporting LLNs increased significantly with higher N-stage (p = .010) and over time (p = .042).ConclusionsThough improving with time, there is still limited consistency in reporting LLNs. Only 44% of primary MRI reports mentioned LLNs and relevant features of those LLNs were seldomly reported. Given the importance of this information for subsequent treatment; increased awareness, proper training and the use of templates are needed.Key Points• Comprehensive reporting of lateral lymph nodes in primary MRI reports was limited to less than 50%.• Lateral lymph nodes are not always discussed during primary multidisciplinary meetings or mentioned in restaging reports.• Improvements in the awareness and knowledge of lateral lymph nodes are needed to ensure adequate multidisciplinary treatment decisions.

Laparoscopic versus open lateral pelvic lymph node dissection in locally advanced rectal cancer: multicentre retrospective cohort study.

BackgroundLateral pelvic lymph node dissection (LPLND) is an option in the treatment of rectal cancer and may reduce local recurrence/improve disease-free survival. Advancements in minimally invasive technology have improved the ability to identify anatomy and neurovascular structures that may help in LPLND. The aim of this retrospective study was to evaluate the technical feasibility and oncological safety of laparoscopic LPLND compared with the open LPLND.MethodBetween July 2010 and July 2019, patients from three tertiary referral hospitals who underwent LPLND with total mesorectal excision for primary rectal cancer were included. Baseline patient characteristics, perioperative outcomes, pathologic results, recurrence, and survival were compared between the laparoscopic and open groups.ResultsThere were 126 and 70 patients in the laparoscopic and open groups respectively. The laparoscopic group had less estimated blood loss (100 ml versus 300 ml, P < 0.001) and lower transfusion rate (0.8 per cent versus 10.0 per cent; P = 0.003) but longer operating times (318 min versus 270 min, P = 0.004). The laparoscopic group had fewer wound infections (1.6 per cent versus 10.0 per cent, P = 0.011) and neuropathy (0 per cent versus 4.3 per cent, P = 0.044). Lateral pelvic recurrence rate was 7.6 per cent in the laparoscopic group and 19.6 per cent in the open group (P = 0.053). Recurrence-free survival (72.2 per cent versus 63.5 per cent; P = 0.190) and overall survival (93.3 per cent versus 85.0 per cent; P = 0.118) were not significantly different.ConclusionLaparoscopic LPLND was associated with improved perioperative outcomes and non-inferior oncological outcomes.

Characteristics and fate of patients with rectal cancer not entering a curative-intent treatment pathway: A complete nationwide registry cohort of 3,304 patients

BackgroundTreatment options for advanced and metastatic rectal cancer have increased during the past decades. However, a considerable proportion of the patients are not eligible for curative treatment, and data on this subset are scarce from a population-based perspective. This study aimed to describe treatment pathways and survival in a national cohort of patients with primary stage IV rectal cancer or stage I-III rectal cancer not eligible for curative treatment. MethodsA national cohort of all patients reported 2008–2015 to the Norwegian Colorectal Cancer Registry with primary metastatic rectal cancer or who did not undergo curative resections for stage I-III rectal cancer was studied with regard to patient characteristics, treatments, and survival. ResultsOf 8291 patients diagnosed with rectal cancer, 3304 (39.9%) were eligible for analysis. The majority (76.8%) had metastatic disease, and 23.2% did not undergo curative resections for other reasons. We identified four main treatment journeys: no tumour-directed treatment, 25.1%; resection of the primary tumour, 44.6%; oncological treatment, 28.4%; and R0 resection of the primary tumour and metastases, 1.9%; these translated into ten different treatment pathways. Survival differed considerably between a median of 5.3 months for M1 disease with non-tumour-directed treatment to a five-year survival of 67% for M1 with R0 resection. ConclusionAlmost 40% of all patients with rectal cancer did not enter a curative-intent treatment pathway. The patient journeys and outcomes varied greatly. This large but understudied population warrants further in-depth analyses of treatment efficacy and effects on quality of life.

Simultaneous or staged resection for synchronous liver metastasis and primary rectal cancer: a propensity score matching analysis

BackgroundColorectal cancer is the third most common cancer in France and by the time of the diagnosis, 15–25% of patients will suffer from synchronous liver metastases. Surgery associated to neoadjuvant treatment can cure these patients, but few studies focus only on rectal cancer. This study was meant to compare the outcomes of patients who underwent a simultaneous resection to those who underwent a staged resection (rectum first or liver first) in the University Hospital of Tours, France.MethodsWe assessed retrospectively a prospective maintained data base about the clinical, pathological and survival outcomes of patients who underwent a simultaneous or a staged resection in our center between 2010 and 2018. A propensity score matching was used, considering the initial characteristics of our groups.ResultsThere were 70 patients (55/15 males, female respectively) with median age 60 (54–68) years. After matching 48 (69%) of them underwent a staged approach and 22 (31%) a simultaneous approach were compared. After PSM, there were 22 patients in each group. No differences were found in terms of morbidity (p = 0.210), overall survival (p = 0.517) and disease-free survival (p = 0.691) at 3 years after matching. There were significantly less recurrences in the simultaneous group (50% vs 81.8%, p = 0.026).ConclusionsSimultaneous resection of the rectal primary cancer and synchronous liver metastases is safe and feasible with no difference in terms of survival.

Artificial intelligence recognition of pathological T stage and tumor invasion in rectal cancer based on large panoramic pathological sections

BackgroundThe incidence of colorectal cancer is increasing worldwide, and it currently ranks third among all cancers. Moreover, pathological diagnosis is becoming increasingly arduous. Artificial intelligence has demonstrated the ability to fully excavate image features and assist doctors in making decisions. Large panoramic pathological sections contain considerable amounts of pathological information. In this study, we used large panoramic pathological sections to establish a deep learning model to assist pathologists in identifying cancerous areas on whole-slide images of rectal cancer, as well as for T staging and prognostic analysis. MethodsWe collected 126 cases of primary rectal cancer from the Affiliated Hospital of Qingdao University West Coast Hospital District (internal dataset) and 42 cases from Shinan and Laoshan Hospital District (external dataset) that had tissue surgically removed from January to September 2019. After sectioning, staining, and scanning, a total of 2350 hematoxylin-eosin-stained whole-slide images were obtained. The patients in the internal dataset were randomly divided into a training cohort (n =88 ) and a test cohort (n =38 ) at a ratio of 7:3. We chose DeepLabV3+ and ResNet50 as target models for our experiment. We used the Dice similarity coefficient, accuracy, sensitivity, specificity, receiver operating characteristic (ROC) curve, and area under the curve (AUC) to evaluate the performance of the artificial intelligence platform in the test set and validation set. Finally, we followed up patients and examined their prognosis and short-term survival to corroborate the value of T-staging investigations. ResultsIn the test set, the accuracy of image segmentation was 95.8%, the Dice coefficient was 0.92, the accuracy of automatic T-staging recognition was 86%, and the ROC AUC value was 0.93. In the validation set, the accuracy of image segmentation was 95.3%, the Dice coefficient was 0.90, the accuracy of automatic classification was 85%, the ROC AUC value was 0.92, and the image analysis time was 0.2 s. There was a difference in survival in patients with local recurrence or distant metastasis as the outcome at follow-up. Univariate analysis showed that T stage, N stage, preoperative carcinoembryonic antigen (CEA) level, and tumor location were risk factors for postoperative recurrence or metastasis in patients with rectal cancer. When these factors were included in a multivariate analysis, only preoperative CEA level and N stage showed significant differences. ConclusionThe deep convolutional neural networks we have establish can assist clinicians in making decisions of T-stage judgment and improve diagnostic efficiency. Using large panoramic pathological sections enables better judgment of the condition of tumors and accurate pathological diagnoses, which has certain clinical application value.

Comparison of Computed and Acquired DWI in the Assessment of Rectal Cancer: Image Quality and Preoperative Staging.

ObjectiveThe aim of the study was to evaluate the computed diffusion-weighted images (DWI) in image quality and diagnostic performance of rectal cancer by comparing with the acquired DWI.MethodsA total of 103 consecutive patients with primary rectal cancer were enrolled in this study. All patients underwent two DWI sequences, namely, conventional acquisition with b = 0 and 1,000 s/mm2 (aDWIb1,000) and another with b = 0 and 700 s/mm2 on a 3.0T MR scanner (MAGNETOM Prisma; Siemens Healthcare, Germany). The images (b = 0 and 700 s/mm2) were used to compute the diffusion images with b value of 1,000 s/mm2 (cDWIb1,000). Qualitative and quantitative analysis of both computed and acquired DWI images was performed, namely, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and signal intensity ratio (SIR), and also diagnostic staging performance. Interclass correlation coefficients, weighted κ coefficient, Friedman test, Wilcoxon paired test, and McNemar or Fisher test were used for repeatability and comparison assessment.ResultsCompared with the aDWIb1,000 images, the cDWIb1,000 ones exhibited significant higher scores of subjective image quality (all P <0.050). SNR, SIR, and CNR of the cDWIb1,000 images were superior to those of the aDWIb1,000 ones (P <0.001). The overall diagnostic accuracy of computed images was higher than that of the aDWIb1,000 images in T stage (P <0.001), with markedly better sensitivity and specificity in distinguishing T1–2 tumors from the T3–4 ones (P <0.050).ConclusioncDWIb1,000 images from lower b values might be a useful alternative option and comparable to the acquired DWI, providing better image quality and diagnostic performance in preoperative rectal cancer staging.

Robotic-assisted laparoscopic surgery for synchronous primary rectal and prostate cancer: Initial case series.

Few studies have reported the simultaneous resection of synchronous rectal and prostate cancers. Here, we report five patients undergoing simultaneous robotic-assisted laparoscopic surgery (RALS) for synchronous rectal and prostate cancer. Rectal cancer operative procedures were high anterior (n =1), intersphincteric (n =2), or abdominoperineal (n =2) resection, followed by radical prostatectomy with vesico-urethral anastomosis. There were no conversions to open surgery, with R0 resection achieved for all rectal cancer cases. The median operative time was 629 (range, 431-764) minutes, and the median estimated blood loss was 100 (range, 20-345) mL. There was one case of colorectal anastomotic leakage requiring covering ileostomy, and two cases of vesico-urethral anastomotic leakage requiring Foley catheter reinsertion. Ileostomies were finally closed in all patients. Pad-free or safety-pad usage for post-surgical urinary incontinence at 6 and 12 months was 3/5 and 5/5, respectively. Simultaneous RALS for synchronous rectal and prostate cancer may offer a safe and feasible approach in selected patients.

Clostridium difficile infection after ileostomy closure and anastomotic failure in rectal cancer surgery patients.

BackgroundDiverting ileostomy during resection of rectal cancer is frequently performed in patients at risk of anastomotic failure. Clostridium difficile infection (CDI) is reported to be frequent in patients who receive ileostomy closure with a questionable association to postoperative anastomosis leak. The primary aim of this study was to determine the incidence of CDI following ileostomy closure in patients who underwent rectal cancer surgery; the secondary aim was to assess the rate of postileostomy closure CDI in patients who presented with leakage at the original colorectal anastomosis site.MethodsMedical records of patients with rectal cancer who underwent ileostomy closure between January 2015 and December 2019 were retrospectively reviewed. All patients had previously received resection and anastomosis for primary rectal cancer with diverting ileostomy. Data regarding CDI incidence, preoperative status, perioperative management, and clinical outcomes were collected. CDI positivity was determined by direct real-time PCR and enzyme-linked fluorescent assays for detecting toxin A and B.Statistical analyses were computed for CDI risk factors.ResultsA total of 1270 patients were included and 208 patients were tested for CDI owing to colitis-related symptoms. The incidence of CDI was 3.6 per cent (46 patients). Multivariable analysis for CDI risk factors identified adjuvant chemotherapy (hazard ratio (HR) 2.28; P = 0.034) and colorectal anastomosis leakage prior to CDI (HR 3.75; P = 0.008). Finally, patients with CDI showed higher colorectal anastomosis leakage risk in multivariable analysis after ileostomy closure (HR 6.922; P = 0.001).ConclusionPatients with CDI presented with a significantly higher rate of colorectal anastomosis leakage prior to ileostomy closure.

The Role of FDG Positron Emission Tomography/Contrast--Enhanced Computed Tomography in Preoperative Staging and Postoperative Follow-up in Rectal Cancer Surgery.

&lt;b&gt; Introduction:&lt;/b&gt; F-18 fluorodeoxyglucose (F18-FDG) positron emission tomography-computed tomography (PET/CT) is a valuable functional imaging modality for the clinical diagnosis which provides physiological information based on the altered tissue metabolism. &lt;/br&gt;&lt;/br&gt; &lt;b&gt; Aim:&lt;/b&gt; This study aims to investigate the effectiveness of F-18 fluorodeoxyglucose (F18-FDG) positron emission tomography-computed tomography (PET/CT) in preoperative staging and postoperative local recurrence and distant metastases in patients with rectal cancer. &lt;/br&gt;&lt;/br&gt; &lt;b&gt; Material and methods:&lt;/b&gt; The imaging of 726 patients with rectal cancer who were operated on at Istanbul University, Istanbul School of Medicine and had F18-FDG PET/CT, CT, and magnetic resonance imaging (MRI) scans between September 2005 and October 2016 were retrospectively analyzed. Of these patients, 170 who had pre- and postoperative PET/CT scans, had their CT scans included in the study. The sensitivity and specificity of PET/CT in preoperative staging and detection of postoperative local recurrence and distant metastases were analyzed. &lt;/br&gt;&lt;/br&gt; &lt;b&gt; Results:&lt;/b&gt; Of the patients, 101 were males and 69 were females with a median age of 62.27 (range, 31 to 89) years. The sensitivity and specificity of preoperative PET/CT in detecting liver metastases were 100% (confidence interval [CI]: 66.37-100%) and 94.2% (CI: 89.72-100%), respectively (Cohen's kappa [κ]: 1.00; P &lt; 0.001). The sensitivity and specificity of postoperative PET/ CT in diagnosing liver metastases were 100% (CI: 88.06-100%) and 98% (CI: 9-100%), respectively (Cohen's κ: 1.00; P &lt; 0.001). The sensitivity and specificity of preoperative PET/CT in detecting lung metastases were 100% (CI: 66.37-100%) and 91.8% (CI: 89.72-100%), respectively (Cohen's κ: 1.00; P &lt; 0.001). The sensitivity and specificity of postoperative PET/CT in detecting lung metastases were 100% (CI: 91.4-100%) and 96% (CI: 95.8-100%), respectively (Cohen's κ: 1.00; P &lt; 0.001). The sensitivity and specificity of PET/CT in preoperative staging of pathological pelvic lymph nodes were 100% (CI: 63.06-100%) and 94.29% (CI: 80.84-99.3%), respectively (Cohen's κ: 0.860; P &lt; 0.001). The sensitivity and specificity of postoperative PET/CT in detecting local recurrences were 100% (CI: 78.2-100%) and 76.74% (CI: 61.37-88.24%), respectively (Cohen's κ: 0.219; P &lt; 0.08). &lt;/br&gt;&lt;/br&gt; &lt;b&gt;Results:&lt;/b&gt; Given the fact that PET/CT can detect all primary rectal cancer in preoperative staging, it can be effectively used in selected cases, particularly in those suspected of local and advanced disease and with metastases (T3N0, T3N1, and/or T4N1). Due to a relatively low specificity in detecting local recurrences postoperatively, PET/CT can be combined with further modalities.

Foley balloons' tamponade is an effective method for controlling massive pelvic bleeding during colorectal surgery.

PurposeHemostasis can be achieved by various methods, but it can be difficult to stop active bleeding in the pelvis. An effective method is described to stop massive active bleeding in the pelvis during colorectal surgery.MethodsWhen there were massive bleedings in the pelvis, 3 to 5 Foley catheters were inserted through stab wounds on the abdomen. The tips of catheters were placed in the pelvis. Each balloon was inflated with 40 mL of sterile water. The water inside each balloon was removed gradually from the third postoperative day. If there is no further bleeding, all catheters were removed on the 7th postoperative day.ResultsThere were 8 patients (4 males and 4 females) with massive pelvic bleeding encountered from January 1998 to December 2018. Four patients underwent low anterior resection for primary rectal cancer, 2 patients for colon cancer with pelvic recurrence, 1 patient for ovary cancer with pelvic recurrence, and 1 patient for presacral parachordoma with a bleeding tendency. All of the patients survived without further bleeding after surgery.ConclusionThe technique is a simple method to control massive pelvic bleeding during colorectal surgery. It is also inexpensive and effective even in patients with a bleeding tendency.

Revised prognostic indicators for treatment of lymph node positive colorectal peritoneal metastases

Peritoneal metastases from colon and rectal cancer presents a new target for a regional approach to treatment. Proper patient selection requires an understanding of the natural history of the disease progression. Data from colorectal cancer patients treated for peritoneal metastases by cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy and the records from the primary colon or rectal cancer surgery were analyzed to assess their impact on survival. Data regarding the anatomic sites of colorectal peritoneal metastases was gathered at the time of a complete CRS. A cohort of 73 patients with peritoneal metastases and lymph node metastases but no liver metastases provided the information. All patients had a complete cytoreduction. Left-sided primary cancer and a complete or near complete response to neoadjuvant chemotherapy (NAC) indicated improved survival. Tumor progression within the abdominal incision, carcinoembryonic antigen (CEA) >10, peritoneal cancer index >9 and peritoneal metastases present in the abdominopelvic regions 6 and 11 carried an especially guarded prognosis. Reduced survival occurred with a right-sided or rectal primary cancer, a CEA >10, tumor cell entrapment, and involvement of abdominopelvic regions 6 and 11. Effective NAC showed a favorable outcome.

Safety, efficacy, and operability of a newly developed absorbable adhesion barrier (GM142) in patients with primary rectal cancer scheduled for diverting ileostomy during laparoscopic surgery: Randomized controlled trial.

AimThe aim of this study was to compare the outcomes of GM142, a newly developed gelatin film with a concave and convex structure to a commercially available conventional film, hyaluronate‐carboxymethylcellulose.MethodsPatients with primary rectal cancer who were scheduled for diverting ileostomy during laparoscopic surgery were eligible for this study. Patients were randomized before surgery and an antiadhesion film was applied under the umbilical incision. The primary outcome was the incidence of adhesion under the midline incision confirmed by second‐look surgery for diverting ileostomy closure. The secondary outcomes were the adhesion severity score, the extent of adhesion score, the presence of intestinal obstruction, and the success of all patching.ResultsA total of 146 patients were enrolled. A total of 123 patients were included in the full analysis set. The primary outcome of “no adhesion” was observed in 66.1% in the GM142 group and 55.7% in the conventional film group. The noninferiority of GM142 to conventional film was confirmed (P = .0005). The secondary outcomes were similar between the groups. For the safety evaluation, there were no safety concerns regarding allergic reactions to gelatin or increased gelatin‐specific IgE antibody titers.ConclusionsThe noninferiority of GM142 to conventional film was shown. GM142 showed no major safety issues. The clinical safety profiles of GM142 suggested certain physiological benefits of the gelatin film as an adhesion barrier.

Updated systematic review of the approach to pelvic exenteration for locally advanced primary rectal cancer

ObjectivesTo review the evidence regarding surgical advances in the management of primary locally advanced rectal cancer. BackgroundThe management of rectal cancer has evolved significantly in recent decades, with improved (neo)adjuvant treatment strategies and enhanced perioperative protocols. Centralization of care for complex, advanced cases has enabled surgeons in these units to undertake more ambitious surgical procedures. MethodsA Pubmed, Ovid, Embase and Cochrane database search was conducted according to the predetermined search strategy. The review protocol was prospectively registered with PROSPERO (CRD42021245582). Results14 studies were identified which reported on the outcomes of 3,188 patients who underwent pelvic exenteration (PE) for primary rectal cancer. 50% of patients had neoadjuvant radiotherapy. 24.2% underwent flap reconstruction, 9.4% required a bony resection and 34 patients underwent a major vascular excision. 73.9% achieved R0 resection, with 33.1% experiencing a major complication. Median length of hospital stay ranged from 13 to 19 days. 1.6% of patients died within 30 days of their operation. Five-year overall survival (OS) rates ranged 29%–78%. LimitationsThe studies included in our review were mostly single-centre observational studies published prior to the introduction of modern neoadjuvant treatment regimens. It was not possible to perform a meta-analysis on the basis that most were non-randomized, non-comparative studies. ConclusionsPelvic exenteration offers patients with locally advanced rectal cancer the chance of long-term survival with acceptable levels of morbidity. Increased experience facilitates more radical procedures, with the introduction of new platforms and/or reconstructive options.

Magnetic resonance neuroimaging promotes the preservation of pelvic autonomic nerves in laparoscopic total mesorectal excision: a comparative study.

BackgroundHow to preserve pelvic autonomic nerves system (PANS) in total mesorectal excision (TME) is still a technical challenge for gastrointestinal surgeons, and nerve preservation according to preoperative magnetic resonance imaging (MRI) is a hot topic in pelvic surgery. The purpose of this study was to assess the postoperative urogenital function of patients with rectal cancer (RC) who underwent preoperative and postoperative neuroimaging of PANS vs. patients who did not.MethodsPatients meeting the inclusion criteria were prospectively enrolled in a magnetic resonance neuroimaging (MRN) group from June 2018, while primary RC patients from January 2016 to May 2018 who met the inclusion criteria were enrolled in a non-MRN group. Patients in the MRN group underwent MRN examination before operation and 6 months after operation, while those in the non-MRN group were collected and analyzed retrospectively.ResultsBased on International Prostate Symptom Score (IPSS) and International Index of Erectile Function 5 (IIEF5) scores at 6 months, the postoperative urinary and sexual function of male patients in the MRN group were significantly better than that in the non-MRN group (P<0.05). In addition, based on International Consultation on Incontinence modular Questionnaire on Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and Female Sexual Function Index (FSFI) scores at 6 months, the postoperative sexual function of female patients in the MRN group was significantly better than that in the non-MRN group (P<0.05).ConclusionsIn the present study, we constructed a three-dimensional (3D) presentation of PANS based on preoperative MRN which showed in vivo pelvic autonomous innervation. This may promote the preservation of PANS during TME and reduce the postoperative urogenital dysfunction rate.

FDG-PET/CT in predicting aggressiveness of rectal cancer

BackgroundTreatment response varies significantly among rectal cancer patients. Tumor can show complete regression, stationary appearance, or even tumour progression during the treatment. It is also widely known that the rate of local recurrence is variable. Precise risk stratification of tumor aggressiveness is required for better per patient tailored treatment plan and predicting the overall prognosis of rectal cancer patients The aim of this study was to assess different parameters of baseline [18F] fluorodeoxyglucose positron emission tomography/computed tomography [(18F) FDG-PET/CT] as a non-invasive tool in predicting aggressiveness of the rectal cancer.ResultsOverall, 33 patients were included [19 moderately differentiated adenocarcinoma, 10 poorly differentiated adenocarcinoma and 4 mucinous adenocarcinomas (MAC)]. SUV estimates (SUV max, SUV mean) were greater in the moderately adenocarcinoma group (p = 0.003 and p = 0.019, respectively). MTV and TLG values were similar between the three histopathological groups (p = 0.763 and p = 0.701, respectively). There was no correlation between SUVmax of primary tumor and MTV (r = 0.034; p = 0.849). However, SUVmax and TLG were significantly correlated (r = 0.517; p = 0.002). Strong correlation between tumor size and MTV (r = 0.489; p = 0.003), and TLG (r = 0.506; p = 0.003) were observed. No significant association was found between MTV and TLG and the clinical stage of rectal cancer.ConclusionBaseline 18F-FDG PET/CT parameters cannot be used alone as a non-invasive diagnostic technique in assessing aggressiveness and prognosis in patients with primary rectal cancer, and further clinical studies are needed before considering the prognostic role of FDG-PET/CT in rectal cancer.

Local Recurrence and Disease-Free Survival After Transanal Total Mesorectal Excision: Results From the International TaTME Registry.

The oncologic safety of transanal total mesorectal excision (TaTME) for rectal cancer has recently been questioned, with high local recurrence (LR) rates reported in Dutch and Norwegian experiences. The objective of this study was to evaluate the oncologic safety of TaTME in a large cohort of patients with primary rectal cancer, primarily in terms of LR, disease-free survival (DFS), and overall survival (OS). This was a prospective international registry cohort study, including all patients who underwent TaTME for primary rectal adenocarcinoma from February 2010 through December 2018. The main endpoints were 2-year LR rate, pattern of LR, and independent risk factors for LR. Secondary endpoints included 2-year DFS and OS rates. Kaplan-Meier survival analysis was used to calculate actuarial LR, DFS, and OS rates. A total of 2,803 patients receiving primary TaTME were included, predominantly men (71%) with a median age of 65 years (interquartile ratio, 57-73 years). After a median follow-up of 24 months (interquartile ratio, 12-38 months), the 2-year LR rate was 4.8% (95% CI, 3.8%-5.8%) with a unifocal LR pattern in 99 of 103 patients (96%). Independent risk factors for LR were male sex, threatened resection margin on baseline MRI, pathologic stage III cancer, and a positive circumferential resection margin on final histopathology. The 2-year DFS and OS rates were 77% (95% CI, 75%-79%) and 92% (95% CI, 91%-93%), respectively. This largest TaTME cohort to date supports the oncologic safety of the TaTME technique for rectal cancer in patients treated in units that contributed to an international registry, with an acceptable 2-year LR rate and a predominantly unifocal LR pattern.

SMAD7 and SMAD4 expression in colorectal cancer progression and therapy response

Inhibitory SMAD7 and common mediator SMAD4 play crucial roles in SMAD-dependent TGF-β signaling that is often disrupted in colorectal cancer (CRC). This study aimed to profile the expression of SMAD7 and SMAD4 in primary and metastatic CRC and to evaluate their significance in disease progression and therapy response. The expression of SMAD7 and SMAD4 genes was analyzed by quantitative real-time PCR in tissues from 35 primary and metastatic CRC patients and in vitro in 7 human cell lines originating from colon tissue. Expression levels of SMAD7 and SMAD4, as well as their ratio, were determined and their association with tumor characteristics and response to therapy were evaluated. SMAD4 level was significantly lower in tumors compared to non-tumor tissues in both primary (p = 0.001) and metastatic (p = 0.001) CRC patients, while tumor expression of SMAD7 was significantly lower from non-tumor tissue only in metastatic patients (p = 0.017). SMAD7/SMAD4 ratio was elevated in CRC primary tumor tissues and cell lines compared to corresponding non-tumor tissues and cell line, respectively (p = 0.003). SMAD7 expression was significantly elevated in primary tumor tissues obtained from responders to neoadjuvant chemoradiotherapy (nCRT) compared to non-responders (p = 0.014). Alterations of expression and ratio of SMAD7 and SMAD4 in CRC cell lines, primary rectal cancer, and liver metastasis emphasize the importance of these genes in different stages of disease progression. Differential expression of SMAD7 in responders versus non-responders to nCRT should be further investigated for its potential predictive value.

Impact of Response to Neo-Adjuvant Therapy to Primary Rectal Cancer on Lung Metastases Treated With SABR

We assessed outcomes in patients undergoing stereotactic ablative radiotherapy (SABR) to lung oligometastatic disease (OMD) of rectal origin in terms of overall survival (OS), progression free survival (PFS) and local control (LC). We assessed if LC and local failure (LF) of lung metastases (LM) is related to primary rectal cancer (PRC) histological response to neo-adjuvant therapy (NAT) to determine if this can act as a biomarker for local response.We undertook a retrospective review of patients with LM from rectal adenocarcinoma treated with SABR at two institutions, with at least 6 months follow up (FU). Data were collected from paper and electronic patient records. Statistical methods used were descriptive analysis, Kaplan Meier, log-rank test and Cox regression.A total of 33 patients with 55 LM were treated with SABR between 2013 and 2020. Median age was 69 (40.8-83.1). Median number of lesions per patient was 1 (1-4). 55% had a single LM. The median dose was 50 Gray in a median of 4 fractions. 21 patients with 35 LM had NA therapy to PRC with available histology. 30 patients (91%) were treated for OMD and 3 were treated for oligoprogression of polymetastatic disease. 33% had synchronous metastases at diagnosis. All patients had a controlled primary rectal cancer having undergone definitive surgery. The median FU was 30.6 months (8.3-94). At the last known FU, 23 patients (69.7%) were alive and 10 (30.3%) had died. The median, 1, 2 and 4-yr OS from SABR were 73 months (95% CI 30.9-115), 100%, 91.8% and 67%, respectively. The LC rate was 89%. There was a LF in 6 of 55 LM, with median time to LF of 11.3 months (2.8-36.1). The only variable associated with LC was response [complete (CR) or partial (PR)] of the PRC to NA therapy. The 2 patients who had no response to NAT both suffered LF of a LM (2 of 3 treated LM). In those with CR or PR (21 patients) there was no LF (0 of 32 treated LM). 2 of 10 patients with no NAT also experienced LF (4 of 18 treated LM). There was 1 patient with no rectal histology available, and 1 patient in whom no details of NAT were available. Neither experienced a LF (2 treated LM). The PFS was 5.97 months (1.6-38.5). None of the analyzed variables were associated with PFS, including PET staging prior to SABR or multiple vs single treated metastasis. 22 (67%) patients progressed post SABR. Pattern of 1st progression: 13 out of field lung (OOF) only; 1 local only; 5 distant only; 1 local and distant; 1 local and OOF; 1 OOF and distant; 11 patients (33%) did not develop further OMD or PMD. No patient experienced > G3 acute toxicity, most common being cough and fatigue.This is the largest reported cohort of rectal cancer patients undergoing lung SABR and the only to review LC in terms of response to NAT to PRC. This offers an insight into response and natural history post SABR for LM that can help inform treatment decisions. We have shown that LC is related to PRC response to NAT, which may act as a biomarker for success of lung SABR. This will need to be confirmed by larger studies.

The efficiency of 18F-FDG-PET/CT in the assessment of tumor response to preoperative chemoradiation therapy for locally recurrent rectal cancer

BackgroundLocally recurrent rectal cancer (LRRC) remains a major problem after curative resection of primary rectal cancer. A noninvasive, prognostic biomarker with which to accurately evaluate disease status and assess the treatment response is critically needed to optimize treatment plans. This study assesses the effectiveness of PET/CT evaluation of preoperative chemoradiation therapy (CRT) in patients with LRRC.MethodsSince 2004, we have been performing preoperative CRT to improve local tumor control and survival. Between 2004 and 2013, 40 patients with LRRC underwent preoperative CRT (radiation: 50 Gy/25 fractions; chemotherapy: irinotecan plus UFT [tegafur and uracil]/leucovorin) and radical surgery, and underwent 18F-FDG-PET/CT before and 3 weeks after the completion of CRT. The maximum standardized uptake values (SUVmax) of the pre-CRT scan (Pre-SUV) and the post-CRT scan (Post-SUV) were measured. The predictive value of the 18F-FDG-PET and CT/MRI response assessments was evaluated.ResultsThe mean Pre-SUV was significantly higher than the Post-SUV (8.2 ± 6.1, vs. 3.8 ± 4.0; P < 0.0001). Following CRT, 17/40 patients (42.5%) were classified as responders according to the Mandard tumor regression grade (TRG1–2). The mean Post-SUV was significantly lower in responders than in nonresponders (2.0 ± 1.7 vs. 5.1 ± 3.9; P = 0.0038). Pathological response was not correlated with the response as evaluated by CT (P > 0.9999) or MRI (P > 0.9999). Multivariate regression analysis identified Post-SUV as an independent predictor of local re-recurrence-free survival (P = 0.0383) and for overall survival (P = 0.0195).ConclusionsPET/CT is useful in assessing tumor response to preoperative CRT for LRRC and predicting prognosis after surgery.

Mutant KRAS as a prognostic biomarker after hepatectomy for rectal cancer metastases: Does the primary disease site matter?

The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown. From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed. A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio [HR]: 1.58, 95% CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95% CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95% CI 1.22-1.99; codon 13, HR 2.10 95% CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy. While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.