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Background: To investigate the clinicopathological features and prognosis of synchronous and metachronous multiple primary colorectal cancer., Materials and Methods: Patients who underwent operation for synchronous and metachronous colorectal cancer at the colorectal surgery department of Shanghai Changhai Hospital between January 2000 and December 2021 were included. Perioperative indicators were comprehensively compared and included in the survival analyses., Results: In total, 563 patients with synchronous ( n =372) and metachronous ( n =191) colorectal cancer were included. Patients with synchronous colorectal cancer were more likely to have a long onset time, positive carcinoembryonic antigen, advanced TNM stage, large tumor, perineural invasion, p53 high expression, and mismatch repair proficient. Compared with metachronous colorectal cancer, patients with synchronous colorectal cancer showed worse 5-year overall survival (68.6±3.0% vs 81.9±3.5%, P =0.018) and 5-year disease-free survival (61.2±3.1% vs 71.0±3.9%, P =0.022). In the subgroup analysis, segmental resection was an independent risk factor for the long-term outcomes of bilateral synchronous colorectal cancer., Conclusions: Clinicopathological and molecular features were different between synchronous and metachronous colorectal cancer. Patients with synchronous colorectal cancer showed a worse prognosis than those with metachronous colorectal cancer. Bilateral synchronous colorectal cancer requires extended resection to achieve improved long-term outcomes., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To investigate the surgical efficacy and prognostic factors of T3NxM0 middle-low rectal cancer without neoadjuvant therapy., Methods: Clinical data of patients with middle-low rectal cancer undergoing TME surgery with T3NxM0 confirmed by postoperative pathology at Colorectal Surgery Department of Changhai Hospital from January 2008 to December 2010 were analyzed retrospectively., Inclusion Criteria: (1)no preoperative neoadjuvant chemoradiotherapy (nCRT); (2) complete preoperative evaluation, including medical history, preoperative colonoscopy or digital examination, blood tumor marker examination, and imaging examination; (3) distance between tumor lower margin and anal verge was ≤ 10 cm; (4) negative circumferential resection margin (CRM-). Finally, a total of 331 patients were included in this study. According to the number of metastatic lymph node confirmed by postoperative pathology, the patients were divided into N0 group without regional lymph node metastasis (190 cases) and N+ group with regional lymph node metastasis (141 cases). The perioperative conditions, local recurrence, distant metastasis and prognostic factors were analyzed., Results: Compared to N0 group in the perioperative data, N+ group had higher ratio of tumor deposit [29.8%(42/141) vs. 0, χ²=64.821, P<0.001] and vascular invasion [7.1%(10/141) vs. 0.5%(1/190),χ²=10.860, P<0.001]. There were no significant differences in tumor diameter, number of lymph nodes detected, positive nerve invasion, degree of tumor differentiation, morbidity of postoperative complication and postoperative adjuvant chemotherapy rate between the two groups (all P>0.05). The median follow-up period was 73.4 months. The merged 5-year local recurrence rate was 2.7%(9/331), 5-year distant metastasis rate was 23.3% (77/331), 5-year disease-free survival (DFS) rate was 73.4%, and 5-year overall survival (OS) rate was 77.2%. Multivariate analysis showed that lymph node metastasis (HR=3.120, 95%CI: 1.918 to 5.075, P<0.001), nerve invasion (HR=0.345, 95%CI: 0.156 to 0.760, P=0.008) and vascular invasion (HR=0.428, 95%CI: 0.189 to 0.972, P=0.043) were independent risk factors for DFS in patients with T3NxM0 rectal cancer after operation. Preoperative carcinoembryonic antigen level (HR=1.858, 95%CI:1.121 to 3.079, P=0.016), lymph node metastasis (HR=3.320, 95%CI: 1.985 to 5.553, P<0.001) and nerve invasion (HR=0.339, 95%CI: 0.156 to 0.738, P=0.006) were independent risk factors for OS in patients with T3NxM0 rectal cancer after operation., Conclusions: Optimal local control rate of middle-low rectal cancer patients with T3NxM0 and CRM- can be achieved by standard TME surgery alone. For patients with preoperative elevated blood carcinoembryonic antigen level, regional lymph node metastasis, or neurovascular invasion confirmed by pathology after surgery, adjuvant chemoradiotherapy should be actively applied after surgery to improve prognosis.

Objective: To investigate the relationship between tumor regression grade (TRG) and lymph node regression grade (LRG) after neoadjuvant chemoradiotherapy (CRT) for rectal cancer and its clinical implication., Methods: Clinicopathological data of 176 rectal cancer patients undergoing radical excision after neoadjuvant CRT from January 2005 to December 2013 in our department were retrospectively analyzed., Inclusion Criteria: (1) Radiology indicated locally advanced low rectal cancer and patients had strong desire to preserve the sphincter before neoadjuvant CRT; (2) there was no definite metastatic lesion before neoadjuvant CRT; (3) patients received whole course of neoadjuvant CRT (regular radiotherapy plus synchronous fluorouracil-like drugs chemotherapy); (4) patients underwent radical operation after neoadjuvant CRT. Patients with short-course CRT and emergency surgery were excluded. TRG and LRG of postoperative specimens (including tumor and lymph nodes) were carried out based on the percentage of the fibrosis and the cancer residue. No cancer residue was defined as TRG1 and LRG1; rare cancer cell residue as TRG2 and LRG2; fibrosis growth over residual cancer as TRG3 and LRG3; residual cancer growth over fibrosis as TRG4 and LRG4; absence of regressive changes as TRG5 and LRG5; and normal lymph nodes as LRG0. Spearman correlation test was used to assess the correlation between TRG and LRG., Results: Of 176 patients, 111 were men and 65 were women. The mean age was (53.9±13.0) years. The number of patients with stage I(, II(, and III( before operation was 10, 49 and 62 while other 55 patients were unknown. Transabdominal low anterior resection (LAR) was performed in 118 cases and abdominal-perineal resection(APR) in 47 cases following the principle of total mesorectal excision (TME). Postoperative pathology of specimens revealed that the number of patients from TRG1 to TRG5 was 19 (10.8%), 25 (14.2%), 66 (37.5%), 47 (26.7%), 19 (10.8%), and from LRG0 to LRG5 was 35 (19.9%), 68 (38.6%), 10 (5.7%), 14 (8.0%), 15(8.5%), 34 (19.3%), respectively. TRG was correlated to LRG (P=0.005) while the Spearman correlation coefficient was only 0.24. The analysis of subgroup without LRG1 also showed that TRG was correlated to LRG(P=0.0005) and the Spearman correlation coefficient was 0.40., Conclusions: TRG can not represent LRG. Therefore, both TRG and LRG should be assessed when evaluating the response of rectal cancer to neoadjuvant CRT.

Objective: To investigate the intramural lateral spread distance in low rectal cancer in order to provide basis for safety lateral resection margin of pull-through conformal resection (PTCR)., Methods: The patients with low rectal cancer who received low anterior resection or abdominal-perineal resection in Changhai Hospital from December 2015 to March 2016 were enrolled and Surgical specimens were collected. After the specimens were fixed in 10% formaldehyde for 24 hours, a piece of tissue that was 1.5 cm in length and 0.5 cm in width from the edge of tumor was cut. The tissue was obtained in the direction of 3, 5, 7 and 9 o'clock clockwise. The distance of intramural lateral spread was measured in the specimens and the risk factors were analyzed., Results: A total of 83 specimens were collected and the overall proportion of intramural lateral spread was 71.1%(59/83). The rate of lateral spread from 3 to 9 o'clock was 34.9%(29/83), 26.5%(22/83), 32.5%(27/83) and 37.3%(31/83) respectively, and the difference was not statistically significant(χ 2 =2.444 9, P=0.485 3). The median distance of lateral spread in each direction was all 0 mm and the quartile range was 1 mm, 0.5 mm, 0.55 mm and 1 mm respectively. The 5th percentile (P5) of each direction was all 0 mm and the 95th percentile(P95) of each direction was 2.5 mm, 1.6 mm, 2.6 mm, 2.5 mm, respectively and the difference was not statistically significant either(χ 2 =5.331 0, P=0.148 9). The rate of lateral spread of T1, T2, T3 and T4 was 0/4, 58.3%(14/24), 83.0%(44/53) and 1/2 respectively, and there was significant difference(P=0.005 0). The multivariate analysis indicated that T stage (P=0.002 2, OR=3.741, 95% CI: 1.606-8.716) was the risk factor of intramural lateral spread., Conclusions: The intramural lateral spread does exist in low rectal cancer and T stage is the risk factor of lateral spread. The lateral resection margin should be 5 mm from the tumor edge at least when PTCR is performed.

Objective: To identify the risk factors associated with lymph node metastasis in rectal cancer after neoadjuvant chemoradiotherapy (CRT)., Methods: From January 2005 to December 2013, the clinical data of 178 patients with advanced rectal cancer undergoing radical excision after neoadjuvant CRT in our department were reviewed retrospectively. A total of 11 clinicopathologic factors relating to lymph node metastasis were studied using univariate and multivariate Logistic regression analyses., Results: There were 74(41.6%) cases with lymph node metastasis, while 104 cases without lymph node metastasis. Univariate analysis showed that age(P=0.000 2), post-CRT CEA level(P=0.011 2), ypT stage(P=0.000 0), pathologic type(P=0.004 0), and tumor regression grade(TRG)(P=0.033 8) were significantly associated with lymph node metastasis. Multivariate analysis showed that age(OR=2.385, 95% CI:1.372 ~ 4.147, P=0.002 1), post-CRT CEA level(OR=2.310, 95% CI:1.005 ~ 5.307, P=0.048 6) and ypT stage(OR=2.592, 95% CI:1.236 ~ 5.432, P=0.011 7) were independent risk factors. However, 15.8% of the patients who achieved TRG1 had lymph node metastasis and TRG failed to independently correlate with lymph node metastasis in rectal cancer after neoadjuvant CRT., Conclusions: There was a higher ratio of lymph node metastasis in rectal cancer patients who were young, CEA≥5 μg/L or deep invasion after neoadjuvant CRT. Therefore, neoadjuvant CRT should be carefully considered in these patients.

Objective: To investigate the risk factors associated with lymph node metastasis of T1 and T2 rectal cancer., Methods: Clinicopathological data of 576 patients with stage T1 to T2 rectal cancer without serosal invasion confirmed by pathology undergoing curative resection in Changhai Hospital from January 1999 to December 2013 were analyzed retrospectively. The relationship of clinicopathological factors of overall patients and stage T1 patients with lymph node metastasis was analyzed by univariate or multivariate analysis., Results: The lymph node metastasis rate of stage T2 rectal cancer was significantly higher than that of stage T1[22.9% (108/463) vs. 9.7%(11/113), P=0.002], and the difference of stage T2a and T2b was not significant[22.0%(38/173) vs. 23.4% (68/290), P=0.733]. Multivariate analysis showed that poor differentiation(HR=1.54, 95% CI:1.12 to 2.13), abnormal carbohydrate antigen (CA) 199 level (HR=2.05, 95% CI:1.16 to 3.62), ulcerative mass (HR=1.58, 95% CI:1.05 to 2.39) and invasion of muscle (of inner ring muscle HR=3.55, 95% CI:1.79 to 7.02; of outer longitudinal muscle, HR=2.35, 95% CI:1.21 to 4.60) were independent risk factors of lymph node metastasis in patients with stage T1-T2 rectal cancer(all P<0.05). Meanwhile poor differentiation(HR=4.43, 95% CI:1.51 to 13.03), abnormal carcinoembryonic antigen(CEA) level (HR=4.66, 95% CI:1.18 to 20.11) and ulcerative mass (HR=6.23, 95% CI:1.51 to 25.66) were risk factors of lymph node metastasis in patients with stage T1 rectal cancer., Conclusion: Poor differentiation, preoperative high CA199, ulcerated tumor, invasion of inner ring muscle or outer longitudinal muscle are risk factors of lymph node metastasis in patients with stage T1-T2 rectal cancer, while the invasion depth of muscularis propria is not risk factor. Besides, poor differentiation, abnormal CEA level, ulcerated tumor are risk factors of lymph node metastasis in stage T1 rectal cancer patients, which can be used as reference for local excision in patients with stage T1 rectal cancer.

Objective: To investigate the expression of RhoA mRNA in colorectal neoplasms., Methods: Total RNA was extracted from 42 surgically resected specimens of colorectal caricinoma and normal mucosa close to the lesions. Afier the optimal reverse transcription polymerase chain reaction (RT-PCR) condition was found, the mRNA expression levels of the RhoA gene in the lesions and the normal mucosa were examined semi-quantitatively and the relation between these expression levels and clinical pathological markers was compared., Results: The expression of RhoA gene mRNA in lesion of colorectal carcinoma was significantly higher than that in contiguous normal mucosa (1.8 +/- 0.6 vs 0.9 +/- 0.4, P < 0.01). The ratio of RhoA expression in neoplasm to that in contiguous mucosa was 2.02 +/- 0.82. Based on this ratio the 42 patients were divided into two groups: overexpression group (19 cases) and high-expression group (23 cases). In the overexpression group the lesions of 14 cases were in Dukes C and Dukes D stages, and lymph node metastasis was found in 13 cases. In the high-expression group, only 9 out of the 23 cases were in advanced stage and 8 cases showed lymph-node metastasis. Chi-squared test analysis demonstrated a significant difference in both aspects between these two groups (P < 0.05). The difference in number of metastatic lymph nodes between the two groups was statistically significant (P < 0.01). Mutation was not found in the RhoA gene sequence examined., Conclusion: RhoA gene may play an important role in colorectal carcinogenesis and correlate with invasion and metastasis of colorectal carcinoma.

Objective: To study the significance of beta -catenin, p53 and PCNA in PJS harmatoma., Method: Paraffin sections of 29 hamartomas of 18 patient with Peutz-Jeghers syndrome, 19 patients with colorectal mucosa and 10 persons with normal mucosa were examined using LSAB. Positive cells were detected under light microscope., Results: All 10 persons with normal mucosa showed p53 negative and beta - catenin positive. The beta - catenin protein was predominantly localized to the plasma membrane. PCNA index (PI) in normal mucosa was 10.56 +/- 7.51. The PI of hamartoma and cancer was 44.57 +/- 21.15 and 32.96 +/- 18.88. The PI of the two groups was significantly higher than that of the normal group. In hamartoma, the positive cells were mainly located in the low 1/3 part of the mucous glands. The positive rate of p53 was 24.1% (7/29) in hamartomatouspolyps and 57.9% (11/19) in colorectal carcinoma (chi(2) = 5.581, P < 0.05). Abnormal expression rate of beta- catenin in colorectal carcinoma was 73.7% (14/19) and 41.3% (12/29) in hamartomatous polyps. Some epithelial cells showed nuclear localization of beta- catenin and concentration of cytoplasm. (chi(2) = 4.825, P < 0.05)., Conclusions: The proliferation activity of hamartomatous polyps increased significantly by multifactory interaction. p53 and beta- catenin play a role in the early stage of hamartoma- adenoma-carcinoma sequence but have a different mechanism in inducing colorectal cancer.