Total neoadjuvant treatment for MRI-stratified high-risk rectal cancer: a single-center, single-arm, prospective Phase II trial (PKUCH-R02).

Background: Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk, locally advanced rectal cancer. However, the benefit of more intensive total neoadjuvant treatment (TNT) is unknown. This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer. Methods: This was a single-center, single-arm, prospective Phase II trial in Peking University Cancer Hospital (Beijing, China). Patients received three cycles of induction oxaliplatin and capecitabine (CapeOX) followed by chemoradiotherapy and two cycles of consolidation CapeOX. The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate, completion of TNT, and pathological downstaging rate. Results: Between August 2017 and August 2018, 68 rectal cancer patients with at least one high risk factor (cT3c/3d/T4a/T4b, cN2, mesorectal fascia involvement, or extramural venous invasion involvement) were enrolled. The overall compliance of receiving the entire treatment was 88.2% (60/68). All 68 patients received induction chemotherapy, 65 received chemoradiotherapy, and 61 received consolidation chemotherapy. The Grade 3-4 adverse event rate was 30.8% (21/68). Nine patients achieved clinical complete response and then watch and wait. Five patients (7.4%) developed distant metastasis during TNT and received palliative chemotherapy. Fifty patients underwent surgical resection. The complete response rate was 27.9%. After a median follow-up of 49.2 months, the overall 3-year disease-free survival rate was 69.7%. Conclusions: For patients with high-risk rectal cancer, this TNT regimen can achieve favorable survival and complete response rates but with high toxicity. However, it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.

Anesthetic management of a patient with preoperative R-on-T phenomenon undergoing laparoscopic-assisted sigmoid colon resection: A case report.

BACKGROUND: The R-on-T phenomenon is a malignant arrhythmia associated with potentially catastrophic consequences. It may initiate ventricular tachycardia or ventricular fibrillation, which can result in syncope or sudden cardiac death. This manifestation poses a great challenge for anesthesiologists. However, it is rarely encountered in the perioperative setting. CASE SUMMARY: We herein present a case in which the R-on-T phenomenon was incidentally revealed by 24-h Holter monitoring in a patient diagnosed with sigmoid colon cancer. Careful evaluation and treatment with mexiletine were carried out preoperatively under consultation with a cardiovascular specialist, and surgery was uneventfully performed under general anesthesia after thorough preparation. CONCLUSION: Physicians should be vigilant about this infrequent but potentially fatal arrhythmia. Our experience suggests that the anesthetic process can be greatly optimized with careful preparation.

Efficacy and safety of preoperative immunotherapy in patients with mismatch repair-deficient or microsatellite instability-high gastrointestinal malignancies.

BACKGROUND: Programmed death protein (PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal malignancies such gastric and colorectal cancer. However, the data on preoperative immunotherapy are limited. AIM: To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy. METHODS: In this retrospective study, we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies. All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively. PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle. RESULTS: Three patients with locally advanced gastric cancer achieved pathological complete response (pCR). Three patients with locally advanced duodenal carcinoma achieved clinical complete response (cCR), followed by watch and wait. Eight of 16 patients with locally advanced colon cancer achieved pCR. All four patients with liver metastasis from colon cancer reached CR, including three with pCR and one with cCR. pCR was achieved in two of five patients with non-liver metastatic colorectal cancer. CR was achieved in four of five patients with low rectal cancer, including three with cCR and one with pCR. cCR was achieved in seven of 36 cases, among which, six were selected for watch and wait strategy. No cCR was observed in gastric or colon cancer. CONCLUSION: Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR, especially in patients with duodenal or low rectal cancer, and can achieve high organ function protection.

Long-term follow-up of HER2 overexpression in patients with rectal cancer after preoperative radiotherapy: A prospective cohort study.

BACKGROUND: The role of HER2 overexpression in rectal cancer is controversial. AIM: To assess the role of HER2 overexpression in the long-term prognosis of rectal cancer. METHODS: Data from patients with locally advanced rectal cancer who underwent total mesorectal excision after short-course radiotherapy at Beijing Cancer Hospital between May 2002 and October 2005 were collected. A total of 151 tissue samples of rectal cancer were obtained using rigid proctoscopy before neoadjuvant radiotherapy, followed by immunohistochemistry and fluorescence in situ hybridisation to determine the patients' HER2 expression status. Univariate and multivariate analyses of the associations between the clinicopathological factors and HER2 status were performed. Survival was estimated and compared using the Kaplan-Meier method based on HER2 expression status, and the differences between groups were verified using the log-rank test. RESULTS: A total of 151 patients were enrolled in this study. A total of 27 (17.9%) patients were ultimately confirmed to be HER2-positive. The follow-up duration ranged from 9 mo to 210 mo, with a median of 134 mo. Distant metastasis and local recurrence occurred in 60 (39.7%) and 24 (15.9%) patients, respectively. HER2 positivity was significantly associated with the pre-treatment lymph node stage (pre-N) (P = 0.040), while there were no differences between HER2 status and age, sex, preoperative CEA levels (pre-CEA), T stage, and lympho-vascular invasion. In terms of prognosis, HER2 overexpression was correlated with distant metastasis (P = 0.002) rather than local recurrence (P > 0.05). The multivariate analysis demonstrated that elevated pre-CEA [P = 0.002, odds ratio (OR) = 3.277, 97.5% confidence interval (CI): 1.543-7.163], post N(+) (P = 0.022, OR = 2.437, 97.5%CI: 1.143-5.308) and HER2(+) (P = 0.003, OR = 4.222, 97.5%CI: 1.667-11.409) were risk factors for distant metastasis. The survival analysis showed that there were significant differences between rectal cancer patients in terms of disease-free survival (DFS) [hazard ratio: 1.69 (95%CI: 0.91-3.14); P = 0.048] and overall survival (OS) [1.95 (1.05-3.63); P = 0.0077]. CONCLUSION: HER2 overexpression is a potential biomarker for predicting lymph node metastasis and distant metastasis, which are associated with worse long-term DFS and OS in rectal cancer patients with locally advanced disease.

Outcome of Surgical Management of Hemophilic Pseudotumor: Review of 10 Cases from Single-Center.

OBJECTIVE: To evaluate the operative methods and clinical results of surgical treatment in a case series of 10 patients with hemophilic pseudotumors. METHODS: Ten patients with hemophilic pseudotumors who received surgical resection treatment in our hospital from October 2017 to June 2020 were retrospectively reviewed. All patients were hemophilia A (factor VIII deficiency).The age range was 20-51 years. Preoperative imaging examination revealed the size of irregular mass from 8.2 cm× 3.3 cm× 2.3 cm to 22.3 cm× 15.5 cm× 17.0 cm. With the supplementary of recombinant coagulation factor VIII, five cases received complete resection; one received resection and skin grafting; one received cytoreduction surgery as the pseudotumor closing to iliac vessel and nerve; three cases received complete resection and construction as bone destruction. The perioperative variables were recorded and all the patients were followed in the outpatient clinic. Clinical and radiological assessments were conducted. RESULTS: In these patients, the average intraoperative blood loss volume was 783.1 mL (range, 240-2100 mL). Six patients received blood transfusion during perioperative period. The average duration of surgery was 140.7 min (range, 110-240 min). All wounds healed smoothly and there was no infection or chronic sinus formation. The average length of hospital stay was 16.3 days (range, 12-25 days). There is no iatrogenic vascular nerve injury in our series. Complete follow-up was performed in all patients. Mean follow-up duration was 14.2 months (range, 6-26 months). One patient with pseudotumor in the thigh had a recurrence 1 year after operation, then secondary operation was performed. In three cases who received complete resection and construction, patient 8 obtained bone graft and late fixation. X-ray examination showed bone formation in the lesion at the 2-year follow-ups after operation. Patient 9 underwent knee replacement, his left knee showed flexion deformity in preoparation. At the last follow-up, range of motion was improved from 0° to 40° compared with preoperative status. Patient 10 had pseudotumor in the distal femur, received long bone graft and intramedullary nail fixation. CONCLUSIONS: Surgical resection for hemophilic pseudotumors is an effective and safe method. The choice of surgical procedure must be individualized according to the localization and progress of pseudotumor.

Efficacy and Safety of Postoperative Intravenous Tranexamic Acid in Total Knee Arthroplasty: A Prospective Randomized Controlled Study.

OBJECTIVE: To assess the efficacy and safety of postoperative intravenous tranexamic acid (TXA) in patients undergoing total knee arthroplasty (TKA). METHODS: From March 2020 to August 2020, all patients undergoing primary unilateral TKA in our hospital were considered in prospective randomized controlled study. Included patients were randomized into three groups to receive either two doses of 15 mg/kg intravenous TXA postoperatively, at 2 and 24 h after closing the incision (group A), or a single dose of 15 mg/kg intravenous TXA 2 h postoperatively (group B), or placebo (group C). The calculated total blood loss (TBL) and hidden blood loss (HBL), incidence of venous thromboembolism (VTE), and transfusion rate were compared among groups. The levels of prothrombotic state parameters including thrombomodulin (TM), thrombin-anti-thrombin complex (TAT), plasmin-anti-plasmin complex (PIC), and tissue-type plasminogen activator-plasminogen activator inhibitor complex (t-PAI·C) in plasma were measured during the perioperative period. Patients were compared depending on the Kellgren-Lawrence classification (K-L types III and IV). RESULTS: All patients were followed up for at least 4 weeks. The mean TBL and HBL in group C (1,182.45 ± 160.50; and 965.47 ± 139.61 mL, respectively) were significantly higher than those in groups A (944.34 ± 130.88 mL, P < 0.05; and 712.45 ± 129.82mL, P < 0.05, respectively) or B (995.20 ± 154.00 mL, P < 0.05; and 757.20 ± 134.39 mL, P < 0.05, respectively), but no significant differences were found between groups A and B (P > 0.05 and P > 0.05, respectively). None of the patients of three groups received blood transfusion, so there were no significant differences in blood transfusion rate among groups. Similar results were obtained with subgroups of patients who had the K-L types III and IV. The DVT frequencies were four, three, and three in groups A, B, and C, respectively, with no significant differences after comparison (P > 0.05). There were no significant differences in the levels of prothrombotic state parameters (TM, TAT, PIC, t-PAI·C) or incidence of VTE among groups (P > 0.05). Wound leakage was observed in five patients during the hospital stay (two patients in group A, one patient in group B, and two patients in group C), and no statistical difference was found in wound leakage or other complications among groups (P > 0.05). CONCLUSIONS: Short-term application of postoperative intravenous TXA in TKAs resulted in reduced HBL without a measured increase in the actual incidence of VTE or the potential risk of thrombosis, but administration of TXA after the first 24 h had no significant effect.

Network Pharmacology-based Research of Active Components of Albiziae Flos and Mechanisms of Its Antidepressant Effect.

Albiziae Flos (AF) has been experimentally proven to have an antidepressant effect. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of action of AF in depression has not been completely deciphered. This study used the network pharmacology method to construct a component-target-pathway network to explore the active components and potential mechanisms of action of AF. The methods included collection and screening of chemical components, prediction of depression-associated targets of the active components, gene enrichment, and network construction and analysis. Quercetin and 4 other active components were found to exert antidepressant effects mainly via monoaminergic neurotransmitters and cAMP signaling and neuroactive ligand-receptor interaction pathways. DRD2, HTR1A, and SLC6A4 were identified as important targets of the studied bioactive components of AF. This network pharmacology analysis provides guidance for further study of the antidepressant mechanism of AF.

Fat clearance and conventional fixation identified ypN0 rectal cancers following intermediate neoadjuvant radiotherapy have similar long-term outcomes.

BACKGROUND: As a prognostic factor for colorectal cancer, lymph node (LN) status, particularly the number of LN harvested, has been demonstrated to be essential in the evaluation of quality control in terms of surgical specimen. Neoadjuvant chemoradiation, however, decreases the LN harvest. Therefore, certain approaches (such as fat clearance or methylene blue) has drawn significant attention in order to raise LN yield. AIM: To compare the long-term oncologic outcome of ypN0 rectal cancer identified using fat clearance (FC) or conventional fixation (CF) following 30 Gy in 10 fractions (30 Gy/10f) of neoadjuvant radiotherapy (nRT). METHODS: Three hundred and eighty-two patients with resectable and locally advanced rectal cancer were treated by 30 Gy/10f intermediate nRT (biologically equivalent dose of 36 Gy) plus total mesorectal excision. Two specimen fixation methods (FC or CF) were non-randomly used. The ypN0 status was identified in 124 and 101 patients in the FL and CF groups, respectively. Primary endpoints were local recurrence-free survival (LRFS) and cancer-specific survival (CSS). RESULTS: The median follow-up of patients was 5.1 years. The median numbers of retrieved LNs in the FC and CF groups were 19.5 (range, 4-47) and 12 (range, 0-44), respectively, with a significant difference (P = 0.000). The percentages of patients with 12 or more retrieved nodes were 82.3% and 50.5% (101/159) in the FC and CF groups, respectively, with a significant difference (P = 0.000). The LRFS at 5 years were 95.7% and 94.6% in the FC and CF groups, respectively, without statistical difference (P = 0.819). The CSS at 5 years were 92.0% and 87.2% in the FC and CF groups, respectively, without statistical difference (P = 0.482). CONCLUSION: For patients with ypN0 rectal cancer who underwent 30 Gy/10f preoperative radiotherapy, the increased retrieval of LNs using fat clearance is not associated with survival benefit. This time-consuming fixation method has a low efficacy as a routine practice.

Significance of HER2 protein expression and HER2 gene amplification in colorectal adenocarcinomas.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal adenocarcinomas (CRCs) remains uncertain, its relevance as a therapeutic target has been established. We undertook the present study to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables. AIM: To correlate HER2 protein expression and HER2 gene amplification with clinicopathological features and survival in surgically resected CRC. METHODS: About 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining (IHC) to assess HER2 protein expression, and 141 selected tumors were further evaluated by fluorescence in situ hybridization (FISH) to assess HER2 gene amplification. Follow-up information was available for 1058 patients, and using this information we investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs, and evaluated the relationship between overexpression and clinicopathological parameters and prognosis. RESULTS: HER2 IHC scores of 3+, 2+, 1+, and 0 were seen in 31 (2.6%), 105 (8.8%), 475 (39.7%), and 584 (48.9%) tumors, respectively. HER2 gene amplification was seen in 24/29 tumors with an IHC score of 3+ (82.8%; unreadable in 2/31), 12/102 tumors with an IHC score of 2+ (11.8%; unreadable in 2/104), and 0 tumors with IHC score of 1+ (0/10). HER2 gene amplification was seen in 36/1191 tumors (3.0%; unreadable in 4/1195). Among the tumors with HER2 IHC scores of 3+ and 2+, the mean percentage of tumor cells with positive IHC staining was 90% (median 100%, range 40%-100%) and 67% (median 75%, range 5%-95%), respectively (P < 0.05). Among tumors with IHC scores of 2+, those with HER2 gene amplification had a higher number of tumors cells with positive IHC staining (n = 12, mean 93%, median 95%, range 90%-95%) than those without (n = 90, mean 70%, median 50%, range 5%-95%) (P < 0.05). HER2 gene status was significantly associated with distant tumor metastasis and stage (P = 0.028 and 0.025). HER2 protein overexpression as measured by IHC or HER2 gene amplification as measured by FISH was not associated with overall survival (OS) or disease-specific survival for the overall group of 1058 patients. However, further stratification revealed that among patients with tubular adenocarcinomas who were 65 years old or younger (n = 601), those exhibiting HER2 gene amplification had a shorter OS than those without (mean: 47.9 mo vs 65.1 mo, P = 0.04). Among those patients with moderately to poorly differentiated tubular adenocarcinomas, those with positive HER2 tumor IHC scores (2+, 3+) had a shorter mean OS than those with negative HER2 IHC scores (0, 1+) (47.2 mo vs 64.8 mo, P = 0.033). Moreover, among patients with T2 to T4 stage tumors, those with positive HER2 IHC scores also had a shorter mean OS than those with negative HER2 IHC scores (47.1 mo vs 64.8 mo, P = 0.031). CONCLUSION: HER2 protein levels are correlated with clinical outcomes, and positive HER2 expression as measured by IHC confers a worse prognosis in those patients 65 years old or younger with tubular adenocarcinomas.

Trans-anal minimally invasive surgery for rectal neoplasia: Experience from single tertiary institution in China.

AIM: To evaluate the feasibility and safety of trans-anal minimally invasive surgery (TAMIS) from single institute in China. METHODS: A retrospective review was conducted for patients with rectal neoplasia, who underwent TAMIS using single incision laparoscopic surgery-Port from January 2013 till January 2016 by a group of colorectal surgeons from Gastrointestinal Center Unit III, Peking University Cancer Hospital. Patients' demographic data, surgical related information, post-operational pathology, as well as peri-operative follow-up were all collected. RESULTS: Twenty-five patients with rectal neoplasia were identified consequently. Complete full-thickness excision was achieved in all cases without conversion. 22 (88%) cases had rectal malignancies [6 were adenocarcinomas and 16 were neuroendocrine tumors (NET)], while 3 patients had adenomas. Mean surgical duration was 61.3 min, and mean post-operative stay were 2.7 d. Post-operational examination demonstrated 5 cases had positive resection margin: 2 adenocarcinoma cases and 1 NET case with positive lateral margin, and the other 2 NET cases with positive basal margin. The curve of operation time for TAMIS cases suggested a minimum of 10 cases for a laparoscopic surgeon proficient with this technique. CONCLUSION: TAMIS was demonstrated to be reproducible and safe, with a relatively short learning process for laparoscopic surgeons in selected cases for rectal neoplasia. Long-term oncological outcome needs to be determined by further investigation.

[Application of Nd:YAP laser in dental pulp revascularization].

PURPOSE: To compare the effect of Nd:YAP laser and Hoshino's triple antibiotic paste on root canal disinfection in the treatment of pulp revascularization, and to provide reference for root canal disinfection in dental pulp revascularization. METHODS: Forty immature permanent teeth diagnosed as acute or chronic periapical periodontitis were included. The periapical lesions and root development were recorded. The cases were divided into 2 groups: the control group and the Nd:YAP laser disinfection experimental group. Clinical examination and X-ray evaluation of each case were performed after treatment. Statistical analysis was performed using SPSS 19.0 software package. RESULTS: Two cases showed symptoms in control group 1 week after treatment, while 4 cases had symptoms in the experimental group. The clinical symptoms disappeared in the control group 2 weeks after treatment, while 1 case still had symptoms in the experimental group. There was no significant difference between the two groups (P>0.05). Clinical evaluation at 18 months of follow-up showed that 2 and 3 cases had recurrent symptoms in the control group and the experimental group, respectively; continuous development of the root was noted in 12 and 10 cases on X-ray film in the control and experimental group, respectively, while 3 and 4 teeth had no obvious root development in the control and experimental group, respectively. There was no significant difference between the control group and the experimental group (P>0.05). CONCLUSIONS: Nd:YAP laser can be used for effective root canal disinfection without obvious effect on the prognosis of dental pulp revascularization.

Risk Factors for Nonclosure of a Temporary Defunctioning Ileostomy Following Anterior Resection of Rectal Cancer.

BACKGROUND: In patients with colorectal cancer, a defunctioning ileostomy is commonly constructed to reduce anastomotic complications. However, many patients do not undergo a subsequent procedure to have their temporary stoma closed. OBJECTIVE: This study investigated the incidence of nonclosure of ileostomies and identified factors associated with nonclosure. DESIGN: This study is a retrospective analysis of prospectively collected data. SETTING: This study was conducted at a tertiary referral cancer hospital. PATIENTS: A total of 296 patients who received anterior resection with a defunctioning ileostomy with protective intention from 2006 to 2013 were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the incidence of nonclosure of ileostomy and associated risk factors. RESULTS: Patients were followed for a median time of 29 months (range, 21-100 months). At the end of the study, 51 (17.2%) patients were left with a permanent ileostomy. The median time interval from the creation of a defunctioning ileostomy to closure was 192 days (range, 14-865 days). Multivariate analyses using a logistic regression model showed that metastatic diseases (OR, 0.179, p < 0.001), Charlson Comorbidity Index score >1 (OR, 0.268; p < 0.01), and complications from the index surgery (OR, 0.391; p = 0.013) were significant independent risk factors for failing to close a defunctioning ileostomy. LIMITATIONS: Although our study has a large patient cohort, it is limited by its retrospective nature. It is difficult to fully evaluate stoma complications after hospital discharge, and the prevalence may be underestimated. CONCLUSION: One in 6 temporary ileostomies constructed during an elective anterior resection for rectal cancer was not closed. Patients should be told before the index surgery that there is a risk of nonclosure and possible complications associated with permanent ileostomy.

[Spatial distribution pattern of soil nitrogen in Huanghuadianzi watershed and related affecting factors].

This research was conducted in Huanghuadianzi watershed in Aohan, Chifeng, Inner Mongolia. Geostatistic was used to study the spatial distribution of soil nitrogen and their affecting factors. The results showed that the soil nitrogen contents in all layers distributed as an island shape, and the high value areas were mainly distributed in the northwest of the watershed as an obvious fertile island shape, while the low value areas were mainly distributed in the south of the watershed. Nitrogen was mainly concentrated in the surface soil, and its content decreased with the increase of soil depth. The soil nitrogen content at first increased then decreased with the altitude, decreased with the slope, and showed the order of shady slope>semi-shady slope>semi-sunny slope> sunny slope in different aspects. The average soil nitrogen contents in different land use types ranked as cropland >woodland > grassland.

Subcutaneous vacuum drains reduce surgical site infection after primary closure of defunctioning ileostomy.

PURPOSE: Surgical site infection (SSI) is the most common complication after primary closure of defunctioning ileostomy. We use a subcutaneous vacuum drain (SVD) in our institution to prevent infection. This study aimed to analyze the risk factors of SSI and to assess the utility of an SVD for preventing SSI in patients undergoing primary closure of ileostomy. METHODS: Patients undergoing ileostomy closure in the Department of Colorectal Surgery, Peking University Cancer Hospital, from September 2006 to March 2013, were included in this study. The clinical features of these patients with or without a subcutaneous drain were reviewed, and the complication rate of SSI was analyzed. The primary endpoints were the incidence and risk factors of SSI, and the secondary endpoints were the rate of overall complications and their management. RESULTS: A total of 245 consecutive patients were enrolled in the study. The overall incidence of SSI was 8.6%. Eighty-five (34.7%) patients received placement of an SVD. The use of SVDs was associated with a significantly lower incidence of SSI compared with primary closure (PC) without an SVD (1.2 vs. 12.5%, p = 0.001). Multivariate analyses showed that the presence of an SVD (odds ratio (OR) 0.063, p = 0.012), total operation time >90 min (OR 4.862, p = 0.002), and postoperative complications (OR 10.576, p < 0.001) were independent risk factors of SSI. CONCLUSIONS: This study shows that an SVD is effective for reducing SSI in patients undergoing PC of ileostomy. Further randomized trials are required to confirm our findings and to compare SVDs with purse-string sutures.

Tumor regression grades: potential outcome predictor of locally advanced rectal adenocarcinoma after preoperative radiotherapy.

AIM: To analyze tumor regression grade (TRG) for prognosis of locally advanced rectal adenocarcinoma (LARA) treated with preoperative radiotherapy. METHODS: One hundred and ninety patients with clinical stage II/III LARA were studied. All patients underwent radical surgery (between 2004 and 2010) after 30-Gy/10-fraction preoperative radiotherapy (pre-RT). All 190 patients received a short course of pre-RT and were reassessed for disease recurrence and survival; the slides of surgical specimens were reviewed and classified according to Mandard TRG. We compared patients with good response (Mandard TRG1 or TRG2) vs patients with bad/poor response (Mandard TRG3-5). Outcomes evaluated were 5-year overall survival (OS), 5-year disease-free survival (DFS), and local, distant and mixed recurrence. Fisher's exact test or χ(2) test, log-rank test and proportional hazards regression analysis were used to calculate the probability that Mandard TRG was associated with patient outcomes. RESULTS: One hundred and sixty-six of 190 patients (87.4%) were identified as Mandard bad responders (TRG3-5). High Mandard grade was correlated with tumor height (41.7% < 6 cm vs 58.3% ≥ 6 cm, P = 0.050), ypT stage (75% ypT0-2 vs 25% ypT3-4, P = 0.000), and ypN stage (75% ypN0 vs 25% ypN1, P = 0.031). In univariate survival analysis, Mandard grade bad responders had significantly worse OS and DFS than good responders (TRG1/2) (OS, 83.1% vs 96.4%, P = 0.000; DFS, 72.3% vs 92.0%, P = 0.002). In multivariate survival analysis, Mandard bad responders had significantly worse DFS than Mandard good responders (DFS 3.8 years (95%CI: 1.2-12.2 years, P = 0.026). CONCLUSION: Mandard grade good responders had a favorable prognosis. TRG may be a potential predictor for DFS in LARA after pre-RT.

Expression of HER-2 in rectal cancers treated with preoperative radiotherapy: a potential biomarker predictive of metastasis.

BACKGROUND: Evidence suggests HER-2 overexpression may be predictive of prognosis in colorectal cancer patients, though this remains controversial. OBJECTIVES: This study was performed to assess the prognostic value of HER-2 expression in locally advanced rectal cancer patients after preoperative radiotherapy. PATIENTS AND METHODS: HER-2 expression was evaluated based on immunohistochemical (IHC) staining of resected specimens from 142 mid-to-low rectal cancer patients. Fluorescence in situ hybridization (FISH) was performed to confirm HER-2 overexpression in samples with an IHC score of 2+. Tumor regression grading (TRG) of the primary tumors was determined semiquantitatively using a tumor regression grading scheme advocated in the AJCC Cancer Staging Manual 7 edition. RESULTS: When the total staining intensity was evaluated, 106 samples (74.6%) showed barely-perceptible positivity (0-1+; HER-2--negative), 15 samples (10.6%) showed moderate positivity (2+) and 21 samples (14.8%) showed strong positivity (3+, HER-2 positive). FISH confirmed that 2 cases showing moderate HER-2 positivity (2+) overexpressed HER2. There was no significant difference between the HER-2 positive and -negative groups with respect to age, gender, TRG, TNM stage, downstaging status, lymphovascular invasion or tumor differentiation. A significant correlation was found between HER-2 overexpression and the incidence of distant metastasis (p = 0.005). Subgroup analysis revealed this correlation was not significant (p = 0.247) in the radiation-insensitive (TRG0-2) subgroup, whereas a significant correlation (p = 0.026) between HER-2 overexpression and distant metastasis was found in the radiation-resistant (TRG3) subgroup. Multivariate analysis identified ypN stage (OR = 0.473, p = 0.002)and overexpression of HER-2 (OR = 3.704, p = 0.008) as independent risk factors for distant metastasis. There was no correlation between HER-2 overexpression and disease-free survival or overall survival among the study population. LIMITATIONS: We reported that HER-2 overexpression was correlated with distant metastasis in rectal cancer patients, especially in the radiation-insensitive group. However, there are certain limitations. First, this study was limited due to the fact that the number of rectal patients enrolled was only 142, which is relatively small. Second, HER-2 expression was measured by IHC with a positive ratio around 15%, which is fairly high according to the literature. Also, we collected the tissue samples preoperatively. It would be interesting to know the HER-2 expression levels pre- and postradiotherapy, as well as their correlation with local recurrence or distant metastasis. Finally, in rectal cancer patients, there is little information published on HER-2 and its role in tumor progression and metastasis. Therefore, we are pursuing the regulatory molecule underlined. CONCLUSIONS: HER-2 is overexpressed in around 15% of rectal cancer patients who receive neoadjuvant radiotherapy. Moreover, HER-2 overexpression could be a predictive biomarker of distant metastasis in rectal cancer patients after preoperative radiotherapy, especially patients showing a poor response to neoadjuvant radiotherapy.

Lymph node distribution and pattern of metastases in the mesorectum following total mesorectal excision using the modified fat clearing technique.

AIM: To define the distribution, size, location and metastasis of lymph nodes (LNs) within the mesorectum from rectal cancer specimens following total mesorectal excision (TME) surgery without neoadjuvant therapy. METHODS: Specimens from 60 patients who underwent TME were treated with modified fat clearing solution to retrieve LNs. The mesorectum was divided into right lateral, anterior, posterior and left lateral sides, which were further subdivided into three levels (upper, middle and lower). RESULTS: 1436 LNs were harvested, including 985 small LNs (<5 mm in size). The number of LNs from the anterior, posterior and bilateral mesorectum was 125 (8.7%), 696 (48.5%) and 615 (42.8%), respectively. In the longitudinal axis, the difference in distribution at the three levels was not significant. 200 LN metastases (mLNs) were detected in 33 patients. 48% (96/200) of these were small LNs. More mLNs, especially small LNs, were shown in the more advanced T stage patients. The mLN metastasis rate was not influenced by tumour level. CONCLUSION: Small LN detection increased the accuracy of N staging by 20% in this study. The incidence of metastasis was the same among the anterior, bilateral and posterior areas of the mesorectum. An increased incidence of mLN metastasis in small LNs was associated with more advanced T staging. mLN metastasis rates in both middle and low rectal cancer were higher in the distal mesorectum than that in the proximal mesorectum. LN number and density were not consistent with spread of the primary tumour. Distal mLNs were found in 35% of cases of both middle and distal rectal cancer, implying a need for TME in both.

[Comparison of short-term postoperative outcomes between hand-assisted laparoscopic and conventional sigmoidectomy].

OBJECTIVE: To compare the safety and efficacy perioperatively between hand-assisted laparoscopic surgery (HALS) and conventional open sigmoidectomy. METHODS: Prospectively collected data on 115 patients with sigmoid colon cancer between January 2009 to June 2010 were analyzed. There were 62 patients in the HALS group and 53 in the conventional sigmoidectomy group (CS). Patient characteristics, operative parameters, and perioperative outcomes were compared. RESULTS: HALS patients were similar to CS patients in age(60.2 yrs vs. 63.4 yrs, P=0.163), gender (53.2% vs. 60.4% male, P=0.441), tumor size (4.7 cm vs. 5.3 cm, P=0.114) and tumor stage. The two groups were comparable in operative time [(122.4±32.0) min vs.(126.7±37.4) min, P=0.510], lymph node harvest (15.1±4.6 vs. 16.8±6.4, P=0.163), free margin length [(4.1±1.8) cm vs.(4.3±1.7) cm, P=0.601], and postoperative complications. However, HALS group had less intraoperative bleeding [(62.6±35.4) ml vs. (168.9±137.1) ml, P=0.000], shorter time to flatus [(2.3±0.8) d vs. (3.3±1.1) d, P=0.000], and shorter hospital stay [(8.8±2.7) d vs.(12.6±8.0) d, P=0.001]. CONCLUSIONS: HALS results in similar short-term outcomes compared to conventional surgery. HALS is safe and minimally invasive.

[Application of hand-assisted laparoscopic surgery (HALS) in colectomy].

OBJECTIVE: To evaluate the safety and efficacy of hand-assisted laparoscopic surgery (HALS) in colorectal tumors. METHODS: Clinical data of 70 patients with colorectal tumors were retrospectively analyzed. All the patients had received HALS colectomy in the Beijing Cancer Hospital. Lapdisc was used for the hand port at the umbilicus. Two additional trocars were used. RESULTS: There were 38 males and 32 females. The median age was 61(29-89) years. Diagnoses included sigmoid cancer(n=48), sigmoid adenoma(n=4), descending colon cancer (n=3), ascending colon cancer (n=1), rectal cancer (n=13), total colectomy(n=1). The operative time was (126.0±22.5) minutes. The intraoperative blood loss was (75.0±18.8) ml. The mean number of lymph node dissection was(16.8±4.2). The median postoperative hospital stay was 9.4 days. There were no perioperative deaths. One patient developed anastomotic stricture and two anastomotic leak, all of which were successfully managed with conservative treatment. CONCLUSION: HALS is a safe and effective technique for colectomy.

[Occult lymph node metastasis in the middle and lower third rectal cancer after neoadjuvant radiotherapy].

OBJECTIVE: To investigate the occult lymph node metastasis in the middle and lower third rectal cancer after neoadjuvant radiotherapy. METHODS: From June 2003 to December 2006, 74 rectal cancer patients received neoadjuvant radiotherapy (30 Gy/10 f/2 w, CACA-CRC-001) and underwent total mesorectal excision (TME) two weeks later. Fat clearance technique was used in all the samples. Occult lymph node metastasis was detected in the mesorectum using the anti-CK antibody. RESULTS: In total 1883 retrieved lymph nodes, 172 metastasis lymph nodes were harvested by HE examination with the mean diameter [(4.9+/-2.6) mm] being larger than that (2.7+/-1.4) mm of the 1711 negative nodes (P<0.01). In HE negative nodes, occult metastasis was found in 40 lymph nodes (2.33%) from 24 patients. Most of these nodes were less than 5 mm (90.0%) with a mean diameter of (3.2+/-1.2)mm, smaller than those of HE-positive metastasis nodes (P<0.01). Occult metastasis was found in 23.1% (9/39) of HE-negative patients. Occult metastasis incidence was higher in patients with HE-positive nodes (42.8%,P<0.01). No correlation of lymph node occult metastasis with tumor differentiation, age, or surgical procedures was found. There was no significant difference in recurrence-free survival between ypN(0) patients with and without occult metastasis (P=0.157). CONCLUSION: It is not necessary to include occult lymph node metastasis in the TNM staging in patients with ypN(0) rectal cancer.