Effect Of Preoperative Chemoradiotherapy Research Articles

Predictors and histological effects of preoperative chemoradiotherapy for rectal cancer and control of lateral lymph node metastasis

IntroductionStandard treatment strategy for low rectal cancer in Japan is different from Western countries. Total mesorectum excision (TME) + lateral lymph node dissection (LLND) is mainly carried out in Japan, whereas neoadjuvant chemoradiotherapy (nCRT) + TME is selected in Western countries. There is no clear definition of preoperative diagnosis of lateral lymph node metastasis. If we can predict lateral lymph node swelling that can be managed by nCRT from lateral lymph node swelling that require surgical resection, clinical benefit is significant. In the current study we assessed characteristics of the lateral lymph node recurrence (LLNR) and LLND that can be managed by nCRT.Patients and MethodsPatients with low rectal cancer (n = 168) underwent nCRT between 2009 and 2016. We evaluated CEA, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lateral lymph node short axis pre and post nCRT, respectively, and also evaluated tumor shrinkage rate, tumor regression grade (TRG). We evaluated the relationship between each and LLNR.ResultsLLND was not carried out all patients. Factors associated with LLNR were PLR and lymph node short axis pre and post nCRT. (p = 0.0269, 0.0278, p < 0.0001, p < 0.0001, respectively). Positive recurrence cut-off values of lateral lymph node short-axis calculated were 11.6 mm pre nCRT and 5.5 mm post nCRT.ConclusionResults suggest that PLR before and after CRT was associated with control of LLNR, and LLND should be performed on lateral lymph nodes with short-axis of 5 mm and 11 mm pre and post nCRT.

Responses of Patients with T3-4N0- 2 M0 Rectal Cancer to Preoperative Chemoradiotherapy: Review of Current Literature

Objective: To investigate the efficacy and safety of chemoradiotherapy and radiotherapy followed by surgery in patients with locally advanced unresectable rectal cancer.Material and method: We reviewed records for 65 patients with locally advanced unresectable rectal cancer treated by preoperative chemoradiotherapy or radiotherapy followed by surgery between 2013 and 2016. Of these, 23 patients were treated with preoperative chemoradiotherapy (40 - 45 Gy) plus concomitant chemotherapy (5Fluorouracil + Calcium Folinate). For comparison, 42 similar patients, treated by preoperative radiotherapy (45 - 50Gy) plus surgery served as control. The primary end-point of the study was overall survival and local control rate.Results: No treatment plan was delayed because of toxicities in both groups. The radical resectability rate was 69.9 % in the chemoradiotherapy group and 33.3 % in the radiotherapy plus surgery group (P = 0. 024). The anal sphincter preservation rates were 26. 6 % and 3. 7 %, respectively (P= 0. 028). The anal sphincter preservation rates of the lower rectal cancer were 27. 3 % and 0. 0 %, respectively (P = 0. 014). Response rates of chemoradiotherapy and radiotherapy plus surgery groups were 82.6 % and 61.9 % (P = 0. 053). The tumor downstage rates were 16 (69.6%) and 24 (57.1%) in these groups (P = 0. 206). The 3-years overall survival rates were 66. 7 % and 55. 6 % (P = 0. 485), and the tumor-free survival rates were 40. 3 % and 33. 1 % (P = 0. 663) . The 3-years local recurrent rates were 26. 9 % and 48. 1 % (P = 0. 174) . No obvious late effects were found in either group. Conclusion: The results of this study suggested at least that acute side effects of preoperative chemoradiotherapy can be tolerated and a higher surgical resection rate can be achieved. However, the chemoradiotherapy did not improve the survival rate while it increased local recurrence due to the high rate of anal sphincter preservation. It is safe and effective to use 5-Fluorouracil + Calcium Folinate and 5 – DFUR as a radiosensitizer during the whole course of radiotherapy.

Abstract PO-046: The effect of neoadjuvant therapy on immune profiling of pancreatic ductal adenocarcinoma: A prospective study of the PREOPANC-1 randomized controlled trial

Abstract The randomized phase III trial (PREOPANC-1) that was performed in 16 centers in the Netherlands compared the effects of preoperative chemoradiotherapy (Gemcitabine and 2.4 Gy radiation) versus immediate surgery for resectable and borderline resectable pancreatic cancer. The outcomes of the secondary endpoints and predefined subgroup analyses suggest an advantage of the neoadjuvant approach. The aim of the present study was to investigate the changes in the immune microenvironment and infiltration caused by the neoadjuvant treatment. To that aim, we collected formalin-fixed, paraffin-embedded pancreatic cancer samples from all centers that participated in the PREOPANC -1 trial. We performed targeted gene expression using the PanCancer Immune Profiling panel of NanoString. Comparing 50 samples of the patient who were subjected to neoadjuvant treatment to 46 treatment-naïve samples showed a distinct genetic profile induced by the neoadjuvant therapy. More than 250 immune-related genes were significantly differentially expressed between the two groups of samples. The results indicate that neoadjuvant therapy resets the innate immune activation in the tissue samples. A significantly higher infiltration of CD14+, CD33+, CSF1R+, and CD163+, MRC1+ cells were found in samples of the neoadjuvant arm. In contrast, B cells and various subtypes of T cells like CD8+ and FOXP3+ showed a significant decrease in the same samples. Pathway analysis revealed that the neoadjuvant treatment stimulated the expression of genes related to the complement activation, chemotaxis, and wound repair, while genes related to lymphocyte activation and adaptive immune responses were dominant in the treatment-naïve arm. In conclusion, this is the first comprehensive study to describe the immune-molecular changes as a result of neoadjuvant therapy in a randomized clinical trial. The results reveal the enrichment of the myeloid compartment following neoadjuvant therapy which was significantly associated with a survival benefit for the patients. Studying the personalized effect of neoadjuvant therapy will guide choosing the appropriate combined therapy for pancreatic cancer. Citation Format: Diba Latifi, Willem de Koning, Sai ping Lau, Frederiek Grevers, Coen van Dam, Casper H. J. van Eijck, Dana A. M. Mustafa. The effect of neoadjuvant therapy on immune profiling of pancreatic ductal adenocarcinoma: A prospective study of the PREOPANC-1 randomized controlled trial [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-046.

Effect of preoperative chemoradiotherapy on the immunological status of rectal cancer patients.

The aim of the study was to investigate the effect of chemo-radiation on the genetic and immunological status of rectal cancer patients who were treated with preoperative chemoradiotherapy (CRT). The expression of immune response-associated genes was compared between rectal cancer patients treated (n = 9) and not-treated (n = 10) with preoperative CRT using volcano plot analysis. Apoptosis and epithelial-to-mesenchymal transition (EMT) marker genes were analysed by quantitative PCR (qPCR). Other markers associated with the tumor microenvironment (TME), such as tumor-infiltrating lymphocytes (TIL) and immune checkpoint molecules, were investigated using immunohistochemistry (IHC). The clinical responses of preoperative CRT for 9 rectal cancer patients were all rated as stable disease, while the pathological tumor regression score (TRG) revealed 6 cases of grade2 and 3 cases of grade1. According to the genetic signature of colon cancers, treated tumors belonged to consensus molecular subtype (CMS)4, while not-treated tumors had signatures of CMS2 or 3. CRT-treated tumors showed significant upregulation of EMT-associated genes, such as CDH2, TGF-beta and FGF, and cancer stem cell-associated genes. Additionally, qPCR and IHC demonstrated a suppressive immunological status derived from the upregulation of inflammatory cytokines (IL-6, IL-10 and TGF-beta) and immune checkpoint genes (B7-H3 and B7-H5) and from M2-type macrophage accumulation in the tumor. The induction of EMT and immune-suppressive status in the tumor after strong CRT treatment urges the development of a novel combined therapy that restores immune-suppression and inhibits EMT, ultimately leading to distant metastasis control.

Oncological Impact of Lateral Lymph Node Dissection After Preoperative Chemoradiotherapy in Patients with Rectal Cancer.

To evaluate the efficacy of selective lateral lymph node dissection (LLND) and the effect of preoperative chemoradiotherapy (PCRT) in patients with LLN ≥ 5mm. Patients who underwent PCRT for rectal cancer were classified: (A) total mesorectal excision (TME)-only with LLN < 5mm (2001-2009, n = 474), (B) TME-only with LLN < 5mm (2011-2016, n = 273), (C) TME-only with LLN ≥ 5mm (2001-2009, n = 102), and (D) TME-LLND with LLN ≥ 5mm (2011-2016, n = 69). Subgroup analysis was performed in patients with LLN ≥ 5mm based on the reduction in LLN size to < 5mm or not on restaging MRI after PCRT. Oncological outcomes did not differ between groups A and B. Group D had lower 3-year local recurrence (LR) (20.13% vs 5.39%, P = 0.0013) and higher relapse-free survival (RFS) (65.83% vs 77.11%, P = 0.0436) than group C, while the 3-year overall survival (OS) was not significantly different between the two groups (87.64% vs 93.53%, P = 0.0670). In patients with reduction of LLN size from ≥ 5mm to < 5mm, LLND significantly reduced LR than did TME alone, but there were no significant differences in survival outcomes. In patients without reduction of LLN size to < 5mm, LLND reduced LR and improved RFS compared with TME alone. Selective LLND reduced LR and improved RFS in patients with LLN ≥ 5mm. Selective LLND reduced LR in patients with reduction of LLN size from ≥ 5mm to < 5mm after PCRT, and improved both LR and RFS in patients without reduction of LLN size to < 5mm.

Preoperative chemoradiotherapy using gemcitabine for pancreatic ductal adenocarcinoma in patients with impaired renal function.

Preoperative chemoradiotherapy (CRT) can be a promising treatment for pancreatic ductal adenocarcinoma (PDAC). However, its administration for patients with impaired renal function has not been well investigated, let alone its clinical effect. We previously reported preliminary feasibility of CRT in PDAC patients with renal impairment. Herein, we aimed to investigate the clinical effects of preoperative CRT including safety and long-term prognosis in more PDAC patients with renal impairment as an extension to our previous work. This study enrolled twenty patients harboring resectable PDAC with creatinine clearance level less than 60ml/min. Patients underwent preoperative CRT with gemcitabine, followed by surgery. The clinical effects of the therapy were evaluated in terms of safety and long-term prognosis. Preoperative CRT was completed in all 20 patients. Grade 4 leukopenia/neutropenia was identified as an observed toxicity in four cases (20.0%). Renal function was not worsened after CRT. After CRT, 17 cases were judged resectable and underwent laparotomy. Pancreatic resection was performed in 15 of the 17 patients; it was not performed in two patients because of peritoneal dissemination. The 1-/3-/5-year cumulative survival rate from the initiation of CRT for the 20 patients was 88.8%/45.5%/22.8%. In the 15 patients, renal function was not worsened after surgery. Our findings suggest that the clinical effects of preoperative CRT would be favorable in PDAC patients with renal impairment.

Effect of preoperative chemoradiotherapy on perioperative outcomes in patients undergoing laparoscopic rectal cancer surgery

Effect of preoperative chemoradiotherapy on perioperative outcomes in patients undergoing laparoscopic rectal cancer surgery

Effects of Preoperative Chemoradiotherapy on the Likelihood of Sphincter Preservation Surgery in Locally Advanced Distal Rectal Cancer: A Longitudinal Study Based on Pelvic Magnetic Resonance Imaging.

It is unclear whether preoperative chemoradiotherapy (pCRT) increases the rate of sphincter-preserving surgery (SPS), avoiding abdominoperineal resection (APR), for the treatment of distal rectal cancer. We examined whether pCRT increases the likelihood of SPS based on changes in tumor height using pelvic magnetic resonance imaging (MRI). Between January 2009 and December 2013, 105 patients underwent long-course pCRT for locally advanced distal rectal cancer (≤5 cm from the anal verge) and were included in this study. The surgical procedures were analyzed in terms of radiologic findings, including the distance from the inferior margin of tumor to the superior margin of the anorectal ring (tumor height) measured by pelvic MRI before and after pCRT. Eighty-six (81.9 %) patients underwent SPS. Overall clinical downstaging occurred in 48 (45.7 %) patients. Tumor height increased significantly after pCRT (from 15.0 ± 15.3 to 18.1 ± 16.9 mm, change 3.1 ± 9.7 mm, p = 0.01). The mean change in tumor height was not significantly different between patients who underwent SPS or APR (mean change 3.3 ± 9.6 vs. 2.3 ± 10.5 mm, p = 0.68). The mean change was significantly greater in the double-stapled anastomosis group than in the handsewn anastomosis group (mean change 5.6 ± 9.9 vs. -0.6 ± 8.6 mm, p = 0.02). This was the first MRI-based longitudinal study to show that pCRT does not appear to increase the likelihood of SPS in locally advanced distal rectal cancer, although it could improve the potential of double-stapled anastomoses.

Effect of preoperative chemoradiotherapy on outcome of patients with locally advanced esophagogastric junction adenocarcinoma-a pilot study.

To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered; indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin-5-fluorouracil-oxaliplatin) for 4 cycles, and concurrent computed tomography-based three-dimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response.

Preoperative Chemoradiotherapy Effects on Anastomotic Leakage After Rectal Cancer Resection

To assess the effects of preoperative chemoradiotherapy (CRT) on anastomotic leakage (AL) after rectal cancer resection, using propensity score matching. Conflicting data have emerged over the last decade regarding the effect of preoperative CRT on AL. We reviewed 1437 consecutive patients with rectal cancer who underwent low anterior resection (LAR) at our institution between 2005 and 2012. AL evaluated as grade C was the primary endpoint, as proposed by the International Study Group of Rectal Cancer in 2010. The patients were treated with (n = 360) or without (n = 1077) preoperative CRT. The total radiation dose was 50.4 Gy in 28 fractions. Multivariate and propensity score matching analyses were used to compensate for the differences in some baseline characteristics. The preoperative CRT group contained more patients with the following characteristics, older age, male sex, smoker, advanced stage tumor, lower/mid rectal tumor location, ultra-LAR, and diverting stoma, than the non-preoperative CRT group (all Ps < 0.05). Postoperative AL occurred in 91 patients (6.3%). Before propensity score matching, the incidence of AL in patients with or without preoperative CRT was 7.5% and 5.9%, respectively (P = 0.293). After propensity score matching, the 2 groups were nearly balanced except for the initial stage and the length of the surgeon's career, and the incidence of AL in patients with or without preoperative CRT was 7.5% and 8.1%, respectively (P = 0.781). We did not observe that preoperative CRT increased the risk of postoperative AL after LAR in patients with rectal cancer, using propensity score matching analysis.

The correlation of neutrophil/lymphocyte ratio and tumor reduction ratio in preoperative chermoradiotherapy for advanced rectal cancer.

633 Background: Preoperative chemoradiotherapy (CRT) is widely used for the treatment of advanced lower rectal cancer and is considered to reduce the local recurrence rate and improve the anus preservation rate. However, the tumor reduction effect varies among patients, and thus far, no factor has yet been found to be effective in the prediction of therapeutic efficacy. Recent studies have shown tumor immunity in the tumor microenvironment to be involved in the anti-tumor effect of radiation and anti-cancer drugs. Among these studies, some show that the neutrophil/lymphocyte (NL) ratio in blood test results correlates with the therapeutic efficacy. We examined the correlation between the NL ratio based on blood test results and tumor-reducing effect of preoperative CRT on advanced lower rectal cancers. Methods: We included 30 advanced lower rectal cancer patients who underwent preoperative CRT during the period ranging from January 2008 to June 2013.For advanced lower rectal cancers classified as cT3orT4NXM0, preoperative CRT was conducted according to the following regimen: 50.4 Gy (1.8 Gy × 28 fr) + UFT (300 mg/day, LV [75 mg/day]) × 28 days. The neutrophil count and lymphocyte count were determined based on the blood tests conducted before and after CRT; the NL ratio was calculated, and the correlation between the value of the ratio and tumor reduction rate was examined. Results: Radical surgery was performed on 28 of the 30 patients who underwent preoperative CRT. One of the 28 patients showed local recurrence (rate, 3.6%). In addition, down stage tumors were found in 16 of the 28 patients, and the down stage rate was 57.1%. Significant differences (p &lt; 0.0001) were found between the tumor reduction effect and NL ratio from blood tests before CRT, as well as between the tumor reduction effect and the ratio from blood tests after CRT. Conclusions: The above findings suggest anti-tumor immunity in the tumor microenvironment, particularly that lymphocytes might be involved in the antitumor effectiveness of preoperative CRT in advanced lower rectal cancers. In addition, NL ratio from blood tests could be a predictive factor of the tumor reduction effect.

Research on clinical and pathological down-staging effects of pre-operative chemoradiotherapy on locally advanced gastric cancer

Objective To investigate the down-staging effects of pre-operative chemoradiotherapy in the treatment of locally advanced gastric cancer.Methods Retrospectively analyzed clinical data about 35 cases of locally advanced gastric cancer in our hospital from January 2009 to January 2013.Observed chemoradiotherapy methods,pathological down-staging,toxicity and exairesis.Results The effective rate of chemoradiotherapy in 35 cases was 54.29％,the disease control rate (DCR) was 80.00％,the down-staging rate was 54.29％,and the resection rate was 88.57％.Adverse reactions mainly focused on myelosuppression and gastrointestinal reactions.Conclusion Pre-operative chemoradiotherapy can reduce neoplasm staging of locally advanced gastric cancer,and is effective in improving the resection rate and prognosis. Key words: Locally advanced gastric cancer; Radiotherapy; Chemotherapy; Neoplasm staging

OC-0417: Effect of preoperative chemoradiotherapy on recurrence pattern in esophageal tumors

OC-0417: Effect of preoperative chemoradiotherapy on recurrence pattern in esophageal tumors

The effect of preoperative chemoradiotherapy on lymph nodes harvested in TME for rectal cancer

BackgroundAdequate lymph nodes resection in rectal cancer is important for staging and local control. This retrospective analysis single center study evaluated the effect of neoadjuvant chemoradiation on the number of lymph nodes in rectal carcinoma, considering some clinicopathological parameters.MethodsA total of 111 patients undergone total mesorectal excision for rectal adenocarcinoma from July 2005 to May 2012 in our center were included. No patient underwent any prior pelvic surgery or radiotherapy. Chemoradiotherapy was indicated in patients with rectal cancer stage II or III before chemoradiation.ResultsOne-hundred and eleven patients were considered. The mean age was 67.6 yrs (range 36 – 84, SD 10.8). Fifty (45.0%) received neoadjuvant therapy before resection. The mean number of removed lymph nodes was 13.6 (range 0–39, SD 7.3). In the patients who received neoadjuvant therapy the number of nodes detected was lower (11.5, SD 6.5 vs. 15.3, SD 7.5, p = 0.006). 37.4% of patients with preoperative chemoradiotherapy had 12 or more lymph nodes in the specimen compared to the 63.6% of those who had surgery at the first step (p: 0.006).Other factors associated in univariate analysis with lower lymph nodes yield included stage (p 0.005) and grade (p 0.0003) of the tumour. Age, sex, tumor site, type of operation, surgeons and pathologists did not weight upon the number of the removed lymph nodes.ConclusionIn TME surgery for rectal cancer, preoperative CRT results into a reduction of lymph nodes yield in univariate analisys and linear regression.

Association between Anal Function and Therapeutic Effect after Preoperative Chemoradiotherapy followed by Intersphincteric Resection

Background/Aims: Preoperative chemoradiotherapy (CRT) for rectal cancer improves local control, but can also induce severe anal dysfunction after surgery. The goal of the study was to assess the relationship of the therapeutic effect of CRT with anal function and prognosis after intersphincteric resection (ISR). Methods: The subjects were 37 patients with lower rectal cancer who underwent ISR with preoperative CRT. The rectal cancer regression grade (RCRG) was quantified based on histologic features of surgical specimens. The relationships of RCRG with anal function (assessed by questionnaire) and incontinence (Wexner score) were examined at 12 months after surgery. Results: The median Wexner scores at 12 months after stoma closure in RCRG1, -2, and -3 cases were 18.0, 7.5, and 4.5, respectively, and anal function differed significantly among these groups (p = 0.001). Four cases had local recurrence, but 5-year local recurrence rates did not differ significantly among the groups. The 5-year disease-free survival rates were 88.9, 50.8, and 50.0% and the 5-year overall survival rates were 100, 77.3, and 66.7% in RCRG1, -2, and -3 cases, respectively, with no significant differences among the groups. Conclusion: Postoperative anal function is decreased when the effect of preoperative CRT is strong in patients treated with ISR.

The effect of preoperative chemoradiotherapy on lymph node harvest in laparoscopic TME for rectal cancer

Background: Adequate lymph node resection is important for tumor staging and local control. The aim of this study was to determine the effect of neoadjuvant chemoradiation on lymph node yield in rectal carcinoma.

The Effects of Preoperative Chemoradiotherapy on Lymph Node Sampling in Rectal Cancer

The current recommendation from the American Joint Committee on Cancer and the International Union Against Cancer is that 12 or more lymph nodes should be examined to appropriately stage rectal cancer. It is unclear if this metric is appropriate or achievable for patients who receive neoadjuvant therapy. The purpose of this study was to review the effects of neoadjuvant chemoradiotherapy on the lymph node yield in patients with rectal cancer. A comprehensive search was made of MEDLINE, PubMed, and Web of Science for articles published through December 2011. The descriptors rectal neoplasms, lymph nodes, lymph node yield, radiotherapy, and neoadjuvant therapy were used to identify articles that reported the lymph node yield with and without neoadjuvant chemoradiotherapy for rectal cancer. Patients received either chemoradiotherapy or no neoadjuvant treatment before undergoing total mesorectal excision for rectal cancer. The main outcome measures included the mean lymph node yield both with and without neoadjuvant treatment, the percentage of patients that received an adequate lymph node dissection, and the number of lymph nodes found to be positive for metastatic disease. A total of 7 studies were included in this review. They demonstrated a decrease in lymph node yield in patients who received neoadjuvant therapy, ranging from 7% to 53% based on the articles in this review. A meta-analysis was not performed because of the limited complete data published on this subject. Consequently, there is heterogeneity in the studies that were selected for this review. Patients with rectal cancer who receive preoperative chemoradiotherapy should be anticipated to have a lower lymph node yield than patients who receive surgery alone. This calls into question if the current guideline of 12 lymph nodes is relevant, in particular, for those patients receiving neoadjuvant therapy.

Differences in tissue degeneration between preoperative chemotherapy and preoperative chemoradiotherapy for colorectal cancer

Preoperative chemoradiotherapy (CRT) for rectal cancer is administered to improve local control, but can also induce severe anal dysfunction after surgery, while preoperative chemotherapy that significantly reduces the primary lesion in rectal cancer has recently been developed. The aim of the study was to examine differences in the effects of preoperative CRT and chemotherapy on tissue degeneration of patients with colorectal cancer. The subjects were 91 patients, including 68 with rectal cancer who underwent internal sphincteric resection with (n = 47, CRT group) or without (n = 21, control group) preoperative CRT, and 23 with colorectal cancer who received preoperative FOLFOX treatment. Peripheral nerve degeneration was evaluated histopathologically using H&E-stained sections, based on karyopyknosis, disparity of the nucleus, denucleation, vacuolar or acidophilic degeneration of the cytoplasm, and adventitial neuronal changes. The incidence of neural degeneration was significantly higher in the CRT group than in the control group and FOLFOX group. There were no differences in any items of neural degeneration between the FOLFOX and control groups. CRT induced marked neural degeneration around the rectal tumor. FOLFOX treatment produced mild neural degeneration similar to that in the control group.

The effect of preoperative chemoradiotherapy on the latency of the genital nerve and the contractility of the anal sphincter

Aim. To study the effect of chemoradiotherapy on the latency of genital nerves and contractility of the anal sphincter in patients with rectal cancer. Methods. Analyzed were 20 cases of rectal cancer T2-3NXM0 (12 males, 8 females). Complex treatment included preoperative chemoradiation therapy (total focal dose 47 Gy, fluorouracil - 2.5-3 g, cisplatin - 90 mg), surgical intervention and postoperative adjuvant chemotherapy for the period from 2009 to 2010. Before the initiation and after the chemoradiotherapy conducted was an evaluation of latency of the genital nerve and needle electromyography of the anal sphincter. Results. Due to the conduction of chemoradiotherapy the median latency of the right branch in males increased significantly from 2.9 to 4.3 ms, in females from 2.1 to 2.4 ms. The increase in the latency of the left branch of the genital nerve was observed in males (from 5.4 to 10.9 ms), while in women registered was a decrease of the indices (from 4.3 to 2.5 ms). A significant reduction of the potential of the external sphincter at rest (from 226.5±157.3 to 196.9±141 mV) and during conation (from 369.7±226.4 to 262.4±138.1 mV), regardless of gender. Conclusion. Conduction of preoperative chemoradiotherapy for cancer of the lower and middle ampullary part of the rectum leads to a decrease in the conduction speed along the genital nerve predominantly in male patients, and is accompanied by a decrease in electrical potentials of the external anal sphincter.

Randomized clinical trial of preoperative chemoradiotherapy by S-1 versus UFT to rectal cancer for personalized therapy.

432 Background: Preoperative chemoradiotherapy (CRT) in rectal cancer reduces the local recurrence rate after operation and preserves the anus, but it is difficult to predict the effects of CRT. Our purpose of this study was to determine the effects and adverse events of CRT (S-1 or UFT) and to predict the response to CRT in rectal cancer by using both miRNA and DNA expression patterns. Methods: Rectal cancer patients (n=60) who underwent preoperative CRT were randomly divided into two groups (40Gy radiotherapy combined with S-1: 31 patients or UFT: 29 patients). The effects and adverse events of CRT were compared between S-1 group and UFT group. Additionally, RNA and DNA isolated from biopsy specimens of rectal cancer before preoperative CRT were hybridized to miRNA and DNA microarrays. Response to CRT was determined by histopathologic examination of surgically resected specimens. Results: Response to CRT determined by histopathologic examination of surgically resected specimens and RECIST were as follows: responders (grade 2 or 3) were 60%(S-1) and 52%(UFT) (p=0.52). Adverse events of CRT did not differ significantly between the 2 groups, and there was no adverse event of grade 3 or 4. As candidate predictive genes, 184 genes (S-1 group) and 193 genes (UFT group) were identified by DNA microarray, while 6 miRNA (S-1 group) and 16 miRNA (UFT group) were isolated by miRNA microarray as candidate predictive miRNA. Conclusions: Preoperative CRT using S-1 or UFT to rectal cancer is effective and the adverse events were acceptable. Expression profiling of both gene and miRNA may predict the effects of preoperative CRT, implicating the possible personalized therapy for patients with rectal cancer.