Treatment Of Advanced Rectal Cancer Research Articles

A pilot study on the safety and efficacy of neoadjuvant chemo‑adoptive immunotherapy for locally advanced rectal cancer.

The safety and efficacy of combination therapy of immune cell therapy and chemotherapy [chemo-adoptive immunotherapy (CAIT)] for patients with stage IV or recurrent colorectal cancer have been reported. In the present study, the safety and efficacy of neoadjuvant CAIT were investigated for preoperative therapy of locally advanced rectal cancer. The study included patients with cT3/T4 or cN (+) rectal adenocarcinoma scheduled for curative surgery. Six patients who consented to participate in the current study were selected as subjects. Neoadjuvant CAIT involves administration of activated autologous lymphocytes, αβ T cells, and mFOLFOX6 every 2 weeks for six courses, followed by surgery 4-6 weeks thereafter. Common Terminology Criteria for Adverse Events grade 3 neutropenia was observed in one patient. Neoadjuvant CAIT and curative surgery were performed on all the patients. The confirmed response rate was 67%. Downstaging was confirmed in five patients (83%). Regarding histological effects, two patients were grade 1a and four were grade 2. Regarding immunological reactions, both CD4+ and CD8+ T cell infiltration rates increased after treatment in three patients on tumor-infiltrating lymphocyte (TIL) analysis. In peripheral blood analysis, the total lymphocyte count was maintained in all patients, and the CD8+ T cell count increased by ≥3 times on the pretreatment count in two patients but may not be associated with changes in TILs. During the median postoperative follow-up duration of 24 months, liver and lung metastases occurred in one patient, but all patients survived. In conclusion, neoadjuvant CAIT (αβ T cells + mFOLFOX6) can be safely administered for the treatment of advanced rectal cancer. Verification of the efficacy of comprehensive immune cell therapy, especially the induction of antitumor immunity for the prevention of recurrence, will be maintained. The current study is registered with the Japan Registry of Clinical Trials (jRCT; ID, jRCTc030190248; January 21, 2019).

Intratumoral Budding and CD8-Positive T-cell Density in Pretreatment Biopsies as a Predictor of Response to Neoadjuvant Chemoradiotherapy in Advanced Rectal Cancer

BackgroundNeoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer. Yet, the response to CRT varies from complete response to zero tumor regression. Materials and MethodsThe impact of intratumoral budding (ITB) and intratumoral CD8+ cell density on response to CRT and survival were evaluated in biopsy samples from 266 patients with advanced rectal cancer who were treated with long-course neoadjuvant CRT. The expression of epithelial-mesenchymal transition (EMT) markers was compared between patients with high and low ITB, using data from 174 patients with RNA sequencing. ResultsHigh ITB was observed in 62 patients (23.3%). There was no association between ITB and CD8+ cell density. The multivariable logistic regression analysis showed that high CD8+ cell density (OR, 2.69; 95% CI, 1.45-4.98; P = .002) was associated with good response to CRT, whereas high ITB (OR, 0.33; 95% CI, 0.14-0.80; P = .014) was associated with poor response. Multivariable Cox regression analysis for survival showed that high CD8+ cell density was associated with better recurrence-free survival (HR, 0.41; 95% CI, 0.24-0.72; P = .002) and overall survival (HR, 0.36; 95% CI, 0.17-0.74; P = .005), but significance values for ITB were marginal (P = .104 for recurrence-free survival and P = .163 for overall survival). The expression of EMT-related genes was not significantly different between patients with high and low ITB. ConclusionITB and CD8+ cell density in biopsy samples may serve as useful biomarkers to predict therapy response in patients with rectal cancer treated with neoadjuvant CRT.

AN0025, a novel antagonist of PGE2-receptor E-type 4 (EP4), in combination with total neoadjuvant treatment of advanced rectal cancer

PurposeTo assess the safety and efficacy of AN0025 in combination with preoperative radiotherapy and chemotherapy in either short course (SCRT) or long course radiotherapy (LCRT) settings for those with locally advanced rectal cancer. Patients and methodsTwenty-eight subjects with locally advanced rectal cancer participated in this multicenter, open-label, Phase Ib trial. Enrolled subjects received either 250 mg or 500 mg of AN0025 once daily for 10 weeks with either LCRT or SCRT with chemotherapy (7 subjects/group). Participants were assessed for safety/efficacy starting from the first dose of study drug administration and were followed for 2 years. ResultsNo treatment-emergent adverse or serious adverse events meeting dose-limiting criteria were observed, with only 3 subjects discontinuing AN0025 treatment due to adverse events. Twenty-five of 28 subjects completed 10 weeks of AN0025 and adjuvant therapy and were evaluated for efficacy. Overall, 36.0% of subjects (9/25 subjects) achieved a pathological complete response or a complete clinical response, including 26.7% of subjects (4/15 subjects who underwent surgery) who achieved a pathological complete response. A total of 65.4% of subjects had magnetic resonance imaging-confirmed down-staging ≤ stage 3 following completion of treatment. With a median follow-up of 30 months. The 12-month disease-free survival and overall survival were 77.5% (95% confidence interval [CI]: 56.6, 89.2) and 96.3% (95% CI: 76.5, 99.5), respectively. ConclusionsTreatment with AN0025 administered for 10 weeks along with preoperative SCRT or LCRT did not appear to worsen the toxicity in subjects with locally advanced rectal cancer, was well-tolerated and showed promise in inducing both a pathological and complete clinical response. These findings suggest its activity deserves further investigation in larger clinical trials.

Expression Levels of GHRH-Receptor, pAkt and Hsp90 Predict 10-Year Overall Survival in Patients with Locally Advanced Rectal Cancer

Rectal cancer constitutes nearly one-third of all colorectal cancer diagnoses, and certain clinical and molecular markers have been studied as potential prognosticators of patient survival. The main objective of our study was to investigate the relationship between the expression intensities of certain proteins, including growth-hormone-releasing hormone receptor (GHRH-R), Hsp90, Hsp16.2, p-Akt and SOUL, in specimens of locally advanced rectal cancer patients, as well as the time to metastasis and 10-year overall survival (OS) rates. We also investigated whether these outcome measures were associated with the presence of other clinical parameters. In total, 109 patients were investigated retrospectively. Samples of pretreatment tumors were stained for the proteins GHRH-R, Hsp90, Hsp16.2, p-Akt and SOUL using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationships between the intensity of expression of biomarkers, clinical parameters, the time to metastasis and the 10-year OS rate. High levels of p-Akt, GHRH-R and Hsp90 were associated with a significantly decreased 10-year OS rate (p = 0.001, p = 0.000, p = 0.004, respectively) and high expression levels of p-Akt and GHRH-R were correlated with a significantly shorter time to metastasis. Tumors localized in the lower third of the rectum were linked to both a significantly longer time to metastasis and an improved 10-year OS rate. Hsp 90, pAkt and GHRH-R as well as the lower-third localization of the tumor were predictive of the 10-year OS rate in locally advanced rectal cancer patients. The GHRH-R and Hsp90 expression levels were independent prognosticators of OS. Our results imply that GHRH-R could play a particularly important role both as a molecular biomarker and as a target for the anticancer treatment of advanced rectal cancer.

Extralevator Abdominoperineal Excision (ELAPE) is Not Superior to Abdominoperineal Excision (APE) in the Era of Neoadjuvant Treatment in Rectal Cancer.

Aim: To evaluate the effect of extralevator abdominoperineal excision of the rectum (ELAPE) on the circumferential resection margin (CRM) and overall survival in comparison to standard abdominoperineal excision of the rectum (APE) in patients with advanced rectal cancer. Material and Methods: This retrospective study encompasses patients with advanced rectal cancer operated on with two different methods: prone Jack-Knife position ELAPE and APE. In part of them, neoadjuvant chemoradiation was conducted. Postoperative patient, tumor, and outcome data were analyzed in terms of differences in CRM positivity and overall survival. Results: Of 67 patients treated with either APE (52) or ELAPE (15), 43 were male and 24 were female. Neoadjuvant treatment was conducted on 49 of the total patients. Complete pathological response (T0) was achieved in 3 patients. Positive CRM was reported in 7 patients (11.5 %), 3 in ELAPE and 4 in APE group (p = 0.348). The overall postoperative complication rate was 56.7%. Mean survival period was 42.2 months. Overall survival rate for both groups was 67.2 %. No statistical differences were seen between the ELAPE and APE procedure in terms of overall survival (p = 0.483). Conclusions: Differences between the use of ELAPE and APE in terms of CRM positivity and overall survival were not statistically significant. Therefore, we conclude that ELAPE is not superior to standard APE in the treatment of advanced rectal cancer.

Artificial intelligence‐based technology to make a three‐dimensional pelvic model for preoperative simulation of rectal cancer surgery using MRI

A new technique that allows visualization of whole pelvic organs with high accuracy and usability is needed for preoperative simulation in advanced rectal cancer surgery. In this study, we developed an automated algorithm to create a three-dimensional (3D) model from pelvic MRI using artificial intelligence (AI) technology. This study included a total of 143 patients who underwent 3D MRI in a preoperative examination for rectal cancer. The training dataset included 133 patients, in which ground truth labels were created for pelvic vessels, nerves, and bone. A 3D variant of U-net was used for the network architecture. Ten patients who underwent lateral lymph node dissection were used as a validation dataset. The correctness of the vascular labelling was assessed for pelvic vessels and the Dice similarity coefficients calculated for pelvic bone. An automatic segmentation algorithm that extracts the artery, vein, nerve, and pelvic bone was developed, automatically producing a 3D image of the entire pelvis. The total time needed for segmentation was 133seconds. The success rate of the AI-based segmentation was 100% for the common and external iliac vessels, but the rates for the vesical vein (75%), superior gluteal vein (60%), or accessory obturator vein (63%) were suboptimal. Regarding pelvic bone, the average Dice similarity coefficient between manual and automatic segmentation was 0.97 (standard deviation 0.0043). Though there is room to improve the segmentation accuracy, the algorithm developed in this study can be utilized for surgical simulation in the treatment of advanced rectal cancer.

Efficacy and Safety of Preoperative Radiotherapy Versus Chemoradiotherapy in Advanced Rectal Cancer: A Meta-analysis of Randomized Controlled Trials.

This meta-analysis was conducted to evaluate the safety and efficacy of preoperative radiotherapy (RT) combined with surgery and preoperative chemoradiotherapy (CRT) combined with surgery for locally advanced rectal cancer. PubMed, EMBASE and Cochrane Library were searched to collect published randomized controlled trials of preoperative radiotherapy or preoperative CRT combined with surgery for the treatment of locally advanced rectal cancer. Studies were screened according to inclusion and exclusion criteria, and quality was evaluated; RevMan 5.3 software was used for meta-analysis. In total, 7 related studies involving 3100 patients with locally advanced rectal cancer were evaluated. The pathological complete response rate, negative lymph node rate, R0 resection rate, and incidence of grade III/IV adverse reactions were lower in the RT group than in the CRT group. In the absence of postoperative chemotherapy, the 5-year local recurrence rate of RT was higher than that of CRT, but there was no significant difference between the groups among those who underwent postoperative chemotherapy. Moreover, there was no significant difference between the groups with regard to the 5-year survival rate, anal-preserving rate, or incidence of anastomotic leakage. Preoperative CRT is better than preoperative RT for the treatment of advanced rectal cancer, though the adverse reaction rate is higher.

Lateral lymph node dissection in advanced low rectal cancer treatment.

Lateral lymph node (LLN) metastasis is a determinant of local recurrence in advanced low rectal cancer. Lateral lymph node dissection (LLND) is effective in removing metastatic lymph nodes, and has been shown to have a decreased local recurrence rate. However, because of its complexity and complications it induces, there is still tremendous controversy about its usage. Neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME) are recommended as a conventional treatment for advanced rectal cancer. However, LLN metastasis and local recurrence still occur despite nCRT with TME. In Japan, TME with LLND is the standard surgical treatment for Stage II/III of advanced low rectal cancer. Before surgery, a proper evaluation of LLN status should be performed. Laparoscopic LLND and robotic-assisted LLND are useful for this. More research is necessary to improve the oncological outcomes of LLND. In this review, we retrospectively examine previous reports about LLND, aiming to emphasize its application prospects to improve patient survival and life quality.

The role of intraoperative radiotherapy in advanced rectal cancer: a meta-analysis.

Patients with locally advanced and locally recurrent rectal cancer (LARC/LRRC) experience higher rates of local recurrence (LR) and poorer overall survival than patients with primary rectal cancer restricted to the mesorectum despite improved neoadjuvant treatment regimens and radical surgical procedures. Intraoperative radiotherapy (IORT) has been suggested as an adjunctive tool in the surgical management of these challenging cases. However, clear evidence regarding the oncological benefit of IORT is sparse. The aim of this review was to update this evidence in the era of standardized neoadjuvant radiotherapy administration. A systematic review of patients who received IORT as part of multimodal treatment for advanced rectal cancer from 2000 to 2020 and an analysis of IORT and surgery/external beam radiotherapy (EBRT) groups was performed. The primary endpoint was the rate of LR between the two groups. Seven papers met the predefined criteria. LR was reduced by the addition of IORT when compared with the surgery/EBRT alone group (14.7% vs. 21.4%; OR 0.55, 95% CI 0.27-1.14; p=0.11). There was no increase in reported genitourinary morbidity, wound issues, pelvic collections or anastomotic leak in those patients who received IORT. Notably, there was no survival difference between the two groups. The addition of IORT to current treatment strategies in the management of patients with LARC/LRRC is associated with a lower rate of locoregional recurrence without increased morbidity. However, this marks a highly selective group of patients, with heterogeneity regarding indications, prior neoadjuvant treatments and/or IORT dosing.

TaTME for the treatment of advanced rectal cancer

Transanal Total Mesorectal Excision (TaTME) is the latest technical evolution in rectal surgery. The technique is now more standardized and consolidated, therefore new advantages, limits and indications are debated METHODS: A 67-year-old female with no previous surgeries or medical diseases was diagnosed with mid-rectal cancer. After neo-adjuvant treatment, clinical re-staging by pelvic MRI showed an involvement of the posterior left mesorectal fascia, already present before the chemoradiation therapy. The patient was scheduled for TaTME. During the transanal procedure, in the posterior left quadrant, the involvement of the mesorectal fascia was clearly identified and removed, by the excision of a small part of the presacral fascia to achieve an oncological radical excision. The final pathological examination showed a negative circumferential resection margin. TaTME is a safe and effective technique for the treatment of rectal cancers. In patients with mesorectal fascia involvement, the direct view of the surgical dissection plane can improve oncological effectiveness and radicality.

Postoperative XELOX therapy for patients with curatively resected high-risk stage II and stage III rectal cancer without preoperative chemoradiation: A prospective, multicenter, open-label, single arm phase II study.

e16039 Background: Preoperative 5-FU-based chemoradiation is currently a standard treatment for advanced rectal cancer, particularly in Western countries. Although it reduced the local recurrence, it could not necessarily improve overall survival. Furthermore, it can also produce adverse effects and long-term sphincter function deficiency. Adjuvant oxaliplatin plus capecitabine (XELOX) is a recommended regimen for patients with curatively resected colon cancer. However, the efficacy of postoperative adjuvant therapy for rectal cancer patients who have not undergone preoperative chemoradiation remains unknown. We aimed to evaluate the efficacy of surgery and postoperative XELOX without preoperative chemoradiation for treating rectal cancer. Methods: We performed a prospective, multicenter, open-label, single arm phase II study. Patients with curatively resected high-risk stages II and III rectal cancer who had not undergone preoperative therapy were treated with a 120 min intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and capecitabine (2,000 mg/m2/day) in 2 divided doses for 14 days of a 3-week cycle, for a total of 8 cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS). Results: Between August 2012 and June 2015, 60 men and 47 women with a median age was 63 years (range: 29–77 years) were enrolled. Ninety-three patients had Eastern Cooperative Oncology Group performance status scores of ‘0’ and 14 had scores of ‘1’. Tumors were located in the upper and lower rectums in 54 and 48 patients, respectively; 8 patients had stage II disease and 99 had stage III. The 3-year DFS was 70.1% (95% confidence interval, 60.8–78.0%) and 33 patients (31%) experienced recurrence, most commonly in the lung (16 patients) followed by local recurrence (9) and hepatic recurrence (7). Conclusions: Postoperative XELOX without preoperative chemoradiation is effective for rectal cancer and provides good 3-year DFS prospects.And this is probably the first and last report in the world for such cases. Trial registration: This clinical trial was registered in the University Hospital Medical Information Network registry system as UMIN000008634 at Aug 06, 2012.

Rectal Cancer: Asynchronous Metastasis to the Temporal Bone, Temporomandibular Joint and Middle Ear

Rectal cancer has the potential to metastasize to multiple anatomical sites. The hallmark of treatment presides with sound oncologic surgery, adjunct with chemotherapy and radiation therapy when indicated. The initial presentation determines the management regimen, consisting of physical examination and diagnostic imaging. A 54-year-old female presented with locally advanced rectal cancer. Upon conclusion of neoadjuvant chemotherapy and radiation therapy, she underwent a low anterior resection with total mesorectal excision. Her surgical margins were negative; however, of the 21 lymph nodes retrieved, 11 were positive for cancer. The patient underwent further adjuvant chemotherapy. 2 years, 8 months later, the patient presented to the emergency department with worsening swelling of the right side of the face, with increasing pain, hearing, and visual impairments. Diagnostic imaging revealed a large lesion in the cranial anatomy, invading the temporal bone, temporomandibular joint, sphenoid bone and anterior superior epitympanum of the right middle ear. The patient underwent operative intervention followed by radiation and chemotherapy. Asynchronous metastasis of rectal cancer to the cranium is a rare finding and an invasion into the temporal bone even more scarcely reported. The prognosis for distant metastatic disease is poor because it involves metastatic spread via the lymph channels or vascular system. Patients that have undergone treatment for advanced rectal cancer must be approached with a high index of suspicion for distant metastatic disease, even in the advent of routine negative surveillance

Management strategies for patients with advanced rectal cancer and liver metastases using modified Delphi methodology: results from the PelvEx Collaborative.

A total of 15-20% of patients with rectal cancer have liver metastases on presentation. The management of these patients is controversial. Heterogeneity in management strategies is considerable, with management often being dependent on local resources and available expertise. Members of the PelvEx Collaborative were invited to participate in the generation of a consensus statement on the optimal management of patients with advanced rectal cancer with liver involvement. Fifteen statements were created for topical discussion on diagnostic and management issues. Panellists were asked to vote on statements and anonymous feedback was given. A collaborative meeting was used to discuss any nuances and clarify any obscurity. Consensus was considered when >85% agreement on a statement was achieved. A total of 135 participants were involved in the final round of the Delphi questionnaire. Nine of the 15 statements reached consensus regarding the management of patients with advanced rectal cancer and oligometastatic liver disease. Routine use of liver MRI was not recommended for patients with locally advanced rectal cancer, unless there was concern for metastatic disease on initial computed tomography staging scan. Induction chemotherapy was advocated as first-line treatment in those with synchronous liver metastases in locally advanced rectal cancer. In the presence of symptomatic primary disease, a diverting stoma may be required to facilitate induction chemotherapy. Overall, only one-quarter of the panellists would consider simultaneous pelvic exenteration and liver resection. This Delphi process highlights the diverse treatment of advanced rectal cancer with liver metastases and provides recommendations from an experienced international group regarding the multidisciplinary management approach.

The impact of early adjuvant chemotherapy in rectal cancer.

Although adjuvant chemotherapy (AC) has been established as a standard of treatment for advanced rectal cancer, there is no guideline regarding the timing of AC initiation. In this study, we aimed to evaluate the oncologic outcome of early AC initiation and clarify the ideal time to AC among rectal cancer patients receiving preoperative chemo-radiotherapy (preCRT). The medical records of 719 patients who underwent curative resection followed by AC for rectal cancer were analyzed retrospectively. Data distributions were compared according to the calculated cut-off for AC initiation, survival results, and chemotherapy-induced toxicity. Additionally, patients were divided into two groups according to preCRT status and compared with respect to differences in the optimal time to AC. Overall, a cut-off time point of 20 days after surgery for AC initiation was identified as the optimal interval; this yielded a significant difference in disease-free survival but no significant difference in AC toxicity. In the cut-off analysis of patients treated without preCRT, 19 days was identified as the optimal time to AC. However, for patients treated with preCRT, no significant value affected the survival outcome. Earlier initiation of AC (within approximately 3 weeks) was associated with better oncological outcomes among patients with rectal cancer. Additionally, the optimal timing of AC was unclear among patients who received preCRT; this might be attributable to an undetermined role of AC after preCRT or the effects of complications such as anastomotic leakage.

Pretreatment MR-Based Radiomics Signature as Potential Imaging Biomarker for Assessing the Expression of Topoisomerase II alpha (TOPO-IIα) in Rectal Cancer.

Rectal cancer (RC) is one of the most common cancers throughout the world. Chemotherapy or neoadjuvant chemotherapy play an important role in the treatment of advanced RC. Whether to add topoisomerase inhibitor to individualized chemotherapy is a puzzling question for clinicians. To investigate whether pretreatment MR-based radiomics signature can assess the expression of topoisomerase II alpha (TOPO-IIα) in RC. Retrospective. In all, 122 patients with RC. Field Strength/Sequence: Pretreatment 3.0T; T2 WI turbo spin echo (TSE) sequence. A training group (n = 85) and a test group (n = 37) with pathologically confirmed RC. Patients underwent TOPO-IIα expression. A total of 180 radiomics features were extracted from oblique axial T2 WI TSE images of the entire primary tumor. The least absolute shrinkage and selection operator (LASSO) regression model was used to reduce the dimension of the data and select the features. The assessment models were established by multivariable logistic regression analysis. The performance of the model was assessed by the receiver operating characteristic (ROC) curve, nomogram, and calibration. The radiomics signature, which consisted of 10 selected optimal features, was significantly associated with TOPO-IIα expression (P < 0.01 for both training and test groups). The area under the curve (AUC), the sensitivity, and the specificity for assessing TOPO-IIα expression, were 0.859, 0.872, and 0.739, respectively, in the training group, while they were 0.762, 0.941, and 0.600 in the test group. The nomogram model of the radiomics signature (Rad-score) had good calibration. Calibration curves were plotted to assess the calibration of the radiomics nomogram that was accompanied with the Hosmer-Lemeshow test (P = 0.52). The proposed pretreatment MR-based radiomics signature was associated with TOPO-IIα expression. A radiomics nomogram might be helpful in the individualized assessment of TOPO-IIα expression in patients with RC. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1881-1889.

Postoperative XELOX therapy for patients with curatively resected high-risk stage II and stage III rectal cancer without preoperative chemoradiation: a prospective, multicenter, open-label, single-arm phase II study

BackgroundPreoperative 5-FU-based chemoradiation is currently a standard treatment for advanced rectal cancer, particularly in Western countries. Although it reduced the local recurrence, it could not necessarily improve overall survival. Furthermore, it can also produce adverse effects and long-term sphincter function deficiency. Adjuvant oxaliplatin plus capecitabine (XELOX) is a recommended regimen for patients with curatively resected colon cancer. However, the efficacy of postoperative adjuvant therapy for rectal cancer patients who have not undergone preoperative chemoradiation remains unknown. We aimed to evaluate the efficacy of surgery and postoperative XELOX without preoperative chemoradiation for treating rectal cancer.MethodsWe performed a prospective, multicenter, open-label, single arm phase II study. Patients with curatively resected high-risk stage II and stage III rectal cancer who had not undergone preoperative therapy were treated with a 120 min intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and capecitabine (2000 mg/m2/day) in 2 divided doses for 14 days of a 3-week cycle, for a total of 8 cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS).ResultsBetween August 2012 and June 2015, 60 men and 47 women with a median age was 63 years (range: 29–77 years) were enrolled. Ninety-three patients had Eastern Cooperative Oncology Group performance status scores of ‘0’ and 14 had scores of ‘1’. Tumors were located in the upper and lower rectums in 54 and 48 patients, respectively; 8 patients had stage II disease and 99 had stage III. The 3-year DFS was 70.1% (95% confidence interval, 60.8–78.0%) and 33 patients (31%) experienced recurrence, most commonly in the lung (16 patients) followed by local recurrence (9) and hepatic recurrence (7).ConclusionsPostoperative XELOX without preoperative chemoradiation is effective for rectal cancer and provides adequate 3-year DFS prospects.Trial registrationThis clinical trial was registered in the University Hospital Medical Information Network registry system as UMIN000008634 at Aug 06, 2012.

MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4

Radioresistance poses a major challenge in the treatment of advanced rectal cancer. Therefore, understanding the detailed mechanisms of radioresistance may improve patient response to irradiation and the survival rate. To identify the novel targets that modulate the radiosensitivity of rectal cancer, we performed small RNA sequencing with human rectal cancer cell lines. Through bioinformatics analysis, we selected microRNA-310a (miR-130a) as a promising candidate to elucidate radioresistance. miR-130a was dramatically upregulated in radiosensitive rectal cancer cells and overexpression of miR-130a promotes rectal cancer cell radiosensitivity. Mechanically, miR-130a reversed the epithelial-mesenchymal transition phenotype of rectal cancer cells following inhibition of cell invasion upon irradiation. Moreover, miR-130a also inhibited the repair of irradiation-induced DNA damage followed by cell death. We identified that SOX4 was a direct target of miR-130a. Overexpression of SOX4 reversed the promotion activity of miR-130a on radiosensitivity. Together, our findings suggest that miR-130a functions as a radiosensitizer in rectal cancer and reveals a potential therapeutic target and preoperative prognostic marker for radiotherapy.

Neoadjuvant radio-chemotherapy prolongs healing of anastomotic leakage after rectal resection treated with endoscopic vacuum therapy.

Background:Neoadjuvant radiochemotherapy (nRCT) is an important component in the treatment of advanced rectal cancer. Endoscopic vacuum therapy (EVT) has become the treatment of choice for anastomotic leakage after rectal resection in many institutions in Germany. Published case series report on average success and stoma reversal rates of more than 80%. However, so far, there is no distinct report on the potential influence of nRCT on EVT.Methods:A total of 11 patients treated with EVT for anastomotic leakage after nRCT and rectal resection were retrospectively compared with a cohort of eight patients with rectal anastomotic leakage without neoadjuvant treatment. Primary endpoints were death, treatment success, and long-term preservation of intestinal continuity. Secondary endpoint was the duration of treatment. Statistical analysis was performed using Statistical Package for Social Science (SPSS) version 23.0.Results:There was no difference in mortality (0%), success rate (90.9% versus 100%, p = 0.381), or long-term preservation of continuity (63.6% versus 62.5%, p = 0.960). After nRCT, patients showed a significant longer duration of EVT (31.1 days versus 15.9 days, p = 0.040) which was associated with a significantly higher number of sponge applications (9.6 versus 5.0, p = 0.042).Conclusions:In our analysis, EVT showed success in over 90% of patients with anastomotic leakage after rectal resection for colorectal cancer, regardless of neoadjuvant treatment. However, in case of anastomotic leakage, nRCT seems to be associated with the need for a significant longer duration of EVT.

Treatment of advanced rectal cancers: Cylindrical abdominoperineal excision of rectum

Introduction: Treatment for patients with locally advanced low lying rectal cancer differs significantly from patients with rectal cancer restricted to the mesorectum. They require multimodality treatment, including preoperative chemo-radiation and extended surgical resection. Cylindrical abdominoperineal excision of rectum (C-APER) along with possible composite pelvic organ resection is a surgical method to remove an adequate circumferential margin.&#x0D; Method: Patients with the diagnosis of advanced rectal cancers over a period of 9 months are included in this study. Therapeutic approach of C-APER is taken for these patients with focus on multimodality treatment protocols to downstage the tumours and extended resections to enable complete removal of all tumour tissue with clear surgical margins. Consecutive review of cases of advanced rectal cancer to their immediate surgical outcome were done.&#x0D; Results: Five patients with compromised CRM in MRI of rectum, 4 were treated with Neoadjuvant FOLFOX 6 regimen chemotherapy 3 cycles and Short course Radiotherapy. All underwent surgery 6-8 weeks after treatment. The pelvic floor was repaired with biological mesh in 1 and synthetic mesh in 4. The pathological stage of disease remained T3 and above despite neoadjuvant treatment in majority of patients but none of them had positive CRM. The wound complication rates were high in the perineum with serous discharge in almost every patient and one patient needing long term vacuum assisted dressing in the community.&#x0D; Conclusion: The surgery is technically feasible with acceptable morbidity in short term with possible long term outcome of reduced loco-regional failure.

Treatment of Advanced Rectal Cancers: Cylindrical abdominoperineal excision of rectum

Treatment for patients with locally advanced low lying rectal cancer differs significantly from patients with rectal cancer restricted to the mesorectum. Surgical resection will be the straightforward option for the early ones but multimodality treatment, including preoperative chemo-radiation and extended surgical resection will be the options for advanced ones. Cylindrical abdominoperineal excision of rectum (C-APER) along with possible composite pelvic organ resection is a surgical method to remove an adequate circumferential margin so to reduce the local recurrence rate and improve long term survival. Adequate preoperative imaging of the pelvis is therefore important to identify these patients and effort should be made to select those patients with advanced tumours with no systemic spread. In this article, we reviewed some consecutive cases of advanced rectal cancer to their immediate surgical outcome.