Long-term outcomes and failure patterns after laparoscopic intersphincteric resection in ultralow rectal cancers.

BACKGROUND: Intersphincteric resection (ISR), the ultimate anus-preserving technique for ultralow rectal cancers, is an alternative to abdominoperineal resection (APR). The failure patterns and risk factors for local recurrence and distant metastasis remain controversial and require further investigation. AIM: To investigate the long-term outcomes and failure patterns after laparoscopic ISR in ultralow rectal cancers. METHODS: Patients who underwent laparoscopic ISR (LsISR) at Peking University First Hospital between January 2012 and December 2020 were retrospectively reviewed. Correlation analysis was performed using the Chi-square or Pearson's correlation test. Prognostic factors for overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using Cox regression. RESULTS: We enrolled 368 patients with a median follow-up of 42 mo. Local recurrence and distant metastasis occurred in 13 (3.5%) and 42 (11.4%) cases, respectively. The 3-year OS, LRFS, and DMFS rates were 91.3%, 97.1%, and 90.1%, respectively. Multivariate analyses revealed that LRFS was associated with positive lymph node status [hazard ratio (HR) = 5.411, 95% confidence interval (CI) = 1.413-20.722, P = 0.014] and poor differentiation (HR = 3.739, 95%CI: 1.171-11.937, P = 0.026), whereas the independent prognostic factors for DMFS were positive lymph node status (HR = 2.445, 95%CI: 1.272-4.698, P = 0.007) and (y)pT3 stage (HR = 2.741, 95%CI: 1.225-6.137, P = 0.014). CONCLUSION: This study confirmed the oncological safety of LsISR for ultralow rectal cancer. Poor differentiation, (y)pT3 stage, and lymph node metastasis are independent risk factors for treatment failure after LsISR, and thus patients with these factors should be carefully managed with optimal neoadjuvant therapy, and for patients with a high risk of local recurrence (N + or poor differentiation), extended radical resection (such as APR instead of ISR) may be more effective.

Fascia- vs vessel-oriented lateral lymph node dissection for rectal cancer: Short-term outcomes and prognosis in a single-center experience.

BACKGROUND: For the management of lateral lymph node (LLN) metastasis in patients with rectal cancer, selective LLN dissection (LLND) is gradually being accepted by Chinese scholars. Theoretically, fascia-oriented LLND allows radical tumor resection and protects of organ function. However, there is a lack of studies comparing the efficacy of fascia-oriented and traditional vessel-oriented LLND. Through a preliminary study with a small sample size, we found that fascia-oriented LLND was associated with a lower incidence of postoperative urinary and male sexual dysfunction and a higher number of examined LLNs. In this study, we increased the sample size and refined the postoperative functional outcomes. AIM: To compare the effects of fascia- and vessel-oriented LLND regarding short-term outcomes and prognosis. METHODS: We conducted a retrospective cohort study on data from 196 patients with rectal cancer who underwent total mesorectal excision and LLND from July 2014 to August 2021. The short-term outcomes included perioperative outcomes and postoperative functional outcomes. The prognosis was measured based on overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 105 patients were included in the final analysis and were divided into fascia- and vessel-oriented groups that included 41 and 64 patients, respectively. Regarding the short-term outcomes, the median number of examined LLNs was significantly higher in the fascia-oriented group than in the vessel-oriented group. There were no significant differences in the other short-term outcomes. The incidence of postoperative urinary and male sexual dysfunction was significantly lower in the fascia-oriented group than in the vessel-oriented group. In addition, there was no significant difference in the incidence of postoperative lower limb dysfunction between the two groups. In terms of prognosis, there was no significant difference in PFS or OS between the two groups. CONCLUSION: It is safe and feasible to perform fascia-oriented LLND. Compared with vessel-oriented LLND, fascia-oriented LLND allows the examination of more LLNs and may better protect postoperative urinary function and male sexual function.

Short- and long-term results of open vs laparoscopic multisegmental resection and anastomosis for synchronous colorectal cancer located in separate segments.

BACKGROUND: It remains unclear whether laparoscopic multisegmental resection and anastomosis (LMRA) is safe and advantageous over traditional open multisegmental resection and anastomosis (OMRA) for treating synchronous colorectal cancer (SCRC) located in separate segments. AIM: To compare the short-term efficacy and long-term prognosis of OMRA as well as LMRA for SCRC located in separate segments. METHODS: Patients with SCRC who underwent surgery between January 2010 and December 2021 at the Cancer Hospital, Chinese Academy of Medical Sciences and the Peking University First Hospital were retrospectively recruited. In accordance with the inclusion and exclusion criteria, 109 patients who received right hemicolectomy together with anterior resection of the rectum or right hemicolectomy and sigmoid colectomy were finally included in the study. Patients were divided into the LMRA and OMRA groups (n = 68 and 41, respectively) according to the surgical method used. The groups were compared regarding the surgical procedure's short-term efficacy and its effect on long-term patient survival. RESULTS: LMRA patients showed markedly less intraoperative blood loss than OMRA patients (100 vs 200 mL, P = 0.006). Compared to OMRA patients, LMRA patients exhibited markedly shorter postoperative first exhaust time (2 vs 3 d, P = 0.001), postoperative first fluid intake time (3 vs 4 d, P = 0.012), and postoperative hospital stay (9 vs 12 d, P = 0.002). The incidence of total postoperative complications (Clavien-Dindo grade: ≥ II) was 2.9% and 17.1% (P = 0.025) in the LMRA and OMRA groups, respectively, while the incidence of anastomotic leakage was 2.9% and 7.3% (P = 0.558) in the LMRA and OMRA groups, respectively. Furthermore, the LMRA group had a higher mean number of lymph nodes dissected than the OMRA group (45.2 vs 37.3, P = 0.020). The 5-year overall survival (OS) and disease-free survival (DFS) rates in OMRA patients were 82.9% and 78.3%, respectively, while these rates in LMRA patients were 78.2% and 72.8%, respectively. Multivariate prognostic analysis revealed that N stage [OS: HR hazard ratio (HR) = 10.161, P = 0.026; DFS: HR = 13.017, P = 0.013], but not the surgical method (LMRA/OMRA) (OS: HR = 0.834, P = 0.749; DFS: HR = 0.812, P = 0.712), was the independent influencing factor in the OS and DFS of patients with SCRC. CONCLUSION: LMRA is safe and feasible for patients with SCRC located in separate segments. Compared to OMRA, the LMRA approach has more advantages related to short-term efficacy.

HAMP as a Prognostic Biomarker for Colorectal Cancer Based on Tumor Microenvironment Analysis.

Colorectal cancer (CRC) is the most common digestive tumor in the world and has a high mortality rate. The development and treatment of CRC are related to the immune microenvironment, but immune response-related prognostic biomarkers are lacking. In this study, we used The Cancer Genome Atlas (TCGA) to explore the tumor microenvironment (TME) and weighted gene coexpression network analysis (WGCNA) to identify significant prognostic genes. We also identified differentially expressed genes in the TCGA data and explored immune-related genes and transcription factors (TFs). Then, we built a TF regulatory network and performed a comprehensive prognostic analysis of an lncRNA-associated competitive endogenous RNA network (ceRNA network) to build a prognostic model. CCR8 and HAMP were identified both in the WGCNA key module and as immune-related genes. HAMP had good prognostic value for CRC and was highly expressed in CRC tissues and had a negative correlation with CD4+ T cells and M0 macrophages based on immunohistochemistry and immunofluorescence staining of clinical specimens.We found that HAMP had high prognostic and therapeutic target value for CRC and was associated with liver metastasis. These analysis results revealed that HAMP may be a candidate immune-related prognostic biomarker for CRC.

Development and Validation of a Nomogram and a Comprehensive Prognostic Analysis of an LncRNA-Associated Competitive Endogenous RNA Network Based on Immune-Related Genes for Locally Advanced Rectal Cancer With Neoadjuvant Therapy.

Colorectal cancer (CRC) is a common digestive tract tumor worldwide. In recent years, neoadjuvant chemoradiotherapy (CRT) has been the most comprehensive treatment for locally advanced rectal cancer (LARC). In this study, we explored immune infiltration in rectal cancer (RC) and identified immune-related differentially expressed genes (IRDEGs). Then, we identified response markers in datasets in GEO databases by principal component analysis (PCA). We also utilized three GEO datasets to identify the up- and downregulated response-related genes simultaneously and then identified genes shared between the PCA markers and three GEO datasets. Based on the hub IRDEGs, we identified target mRNAs and constructed a ceRNA network. Based on the ceRNA network, we explored prognostic biomarkers to develop a prognostic model for RC through Cox regression. We utilized the specimen to validate the expression of the two biomarkers. We also utilized LASSO regression to screen hub IRDEGs and built a nomogram to predict the response of LARC patients to CRT. All of the results show that the nomogram and prognostic model offer good prognostic value and that the ceRNA network can effectively highlight the regulatory relationship. hsa-mir-107 and WDFY3-AS2 may be prognostic biomarkers for RC.

Classification and genetic counselling for a novel splicing mutation of the MLH1 intron associated with Lynch syndrome in colorectal cancer.

BACKGROUND: Lynch-syndrome-associated cancer is caused by germline pathogenic mutations in mismatch repair genes. The major challenge to Lynch-syndrome screening is the interpretation of variants found by diagnostic testing. This study aimed to classify the MLH1 c.1989 + 5G>A mutation, which was previously reported as a variant of uncertain significance, to describe its clinical phenotypes and characteristics, to enable detailed genetic counselling. METHODS: We reviewed the database of patients with Lynch-syndrome gene detection in our hospital. A novel variant of MLH1 c.1989 + 5G>A identified by next-generation sequencing was further investigated in this study. Immunohistochemical staining was carried out to assess the expression of MLH1 and PMS2 protein in tumour tissue. In silico analysis by Alamut software was used to predict the MLH1 c.1989 + 5G>A variant function. Reverse transcription-polymerase chain reaction and sequencing of RNA from whole blood were used to analyse the functional significance of this mutation. RESULTS: Among affected family members in the suspected Lynch-syndrome pedigree, the patient suffered from late-stage colorectal cancer but had a good prognosis. We found the MLH1 c.1989 + 5G>A variant, which led to aberrant splicing and loss of MLH1 and PMS2 protein in the nuclei of tumour cells. An aberrant transcript was detectable and skipping of MLH1 exon 17 in carriers of MLH1 c.1989 + 5G>A was confirmed. CONCLUSIONS: MLH1 c.1989 + 5G>A was detected in a cancer family pedigree and identified as a pathological variant in patients with Lynch syndrome. The mutation spectrum of Lynch syndrome was enriched through enhanced genetic testing and close surveillance might help future patients who are suspected of having Lynch syndrome to obtain a definitive early diagnosis.

Low ligation has a lower anastomotic leakage rate after rectal cancer surgery.

BACKGROUND: For laparoscopic rectal cancer surgery, the inferior mesenteric artery (IMA) can be ligated at its origin from the aorta [high ligation (HL)] or distally to the origin of the left colic artery [low ligation (LL)]. Whether different ligation levels are related to different postoperative complications, operation time, and lymph node yield remains controversial. Therefore, we designed this study to determine the effects of different ligation levels in rectal cancer surgery. AIM: To investigate the operative results following HL and LL of the IMA in rectal cancer patients. METHODS: From January 2017 to July 2019, this retrospective cohort study collected information from 462 consecutive rectal cancer patients. According to the ligation level, 235 patients were assigned to the HL group while 227 patients were assigned to the LL group. Data regarding the clinical characteristics, surgical characteristics and complications, pathological outcomes and postoperative recovery were obtained and compared between the two groups. A multivariate logistic regression analysis was performed to evaluate the possible risk factors for anastomotic leakage (AL). RESULTS: Compared to the HL group, the LL group had a significantly lower AL rate, with 6 (2.8%) cases in the LL group and 24 (11.0%) cases in the HL group (P = 0.001). The HL group also had a higher diverting stoma rate (16.5% vs 7.5%, P = 0.003). A multivariate logistic regression analysis was subsequently performed to adjust for the confounding factors and confirmed that HL (OR = 3.599; 95%CI: 1.374-9.425; P = 0.009), tumor located below the peritoneal reflection (OR = 2.751; 95%CI: 0.772-3.985; P = 0.031) and age (≥ 65 years) (OR = 2.494; 95%CI: 1.080-5.760; P = 0.032) were risk factors for AL. There were no differences in terms of patient demographics, pathological outcomes, lymph nodes harvested, blood loss, hospital stay and urinary function (P > 0.05). CONCLUSION: In rectal cancer surgery, LL should be the preferred method, as it has a lower AL and diverting stoma rate.

Differential Expression Analysis Revealing CLCA1 to Be a Prognostic and Diagnostic Biomarker for Colorectal Cancer.

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract and lacks specific diagnostic markers. In this study, we utilized 10 public datasets from the NCBI Gene Expression Omnibus (NCBI-GEO) database to identify a set of significantly differentially expressed genes (DEGs) between tumor and control samples and WGCNA (Weighted Gene Co-Expression Network Analysis) to construct gene co-expression networks incorporating the DEGs from The Cancer Genome Atlas (TCGA) and then identify genes shared between the GEO datasets and key modules. Then, these genes were screened via MCC to identify 20 hub genes. We utilized regression analyses to develop a prognostic model and utilized the random forest method to validate. All hub genes had good diagnostic value for CRC, but only CLCA1 was related to prognosis. Thus, we explored the potential biological value of CLCA1. The results of gene set enrichment analysis (GSEA) and immune infiltration analysis showed that CLCA1 was closely related to tumor metabolism and immune invasion of CRC. These analysis results revealed that CLCA1 may be a candidate diagnostic and prognostic biomarker for CRC.

Impact of interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients.

BACKGROUND: Epidemiologically, in China, locally advanced rectal cancer is a more common form of rectal cancer. Preoperative neoadjuvant concurrent chemoradiotherapy can effectively reduce the size of locally invasive tumors and improve disease-free survival (DFS) and pathologic response after surgery. At present, this modality has become the standard protocol for the treatment of locally advanced rectal cancer in many centers, but the optimal time for surgery after neoadjuvant therapy is still controversial. AIM: To investigate the impact of time interval between neoadjuvant therapy and surgery on DFS and pathologic response in patients with locally advanced rectal cancer. METHODS: A total of 231 patients who were classified as having clinical stage II or III advanced rectal cancer and underwent neoadjuvant chemoradiation followed by surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from November 2014 to August 2017 were involved in this retrospective cohort study. The patients were divided into two groups based on the different time intervals between neoadjuvant therapy and surgery: 139 (60.2%) patients were in group A (≤ 9 wk), and 92 (39.2%) patients were in group B (> 9 wk). DFS and pathologic response were analyzed as the primary endpoints. The secondary endpoints were postoperative complications and sphincter preservation. RESULTS: For the 231 patients included, surgery was performed at ≤ 9 wk in 139 (60.2%) patients and at > 9 wk in 92 (39.8%). The patients' clinical characteristics, surgical results, and tumor outcomes were analyzed through univariate analysis combined with multivariate regression analysis. The overall pathologic complete response (pCR) rate was 27.2% (n = 25) in the longer time interval group (> 9 wk) and 10.8% (n = 15) in the shorter time interval group (≤ 9 wk, P = 0.001). The postoperative complications did not differ between the groups (group A, 5% vs group B, 5.4%; P = 0.894). Surgical procedures for sphincter preservation were performed in 113 (48.9%) patients, which were not significantly different between the groups (group A, 52.5% vs group B, 43.5%; P = 0.179). The pCR rate was an independent factor affected by time interval (P = 0.009; odds ratio [OR] = 2.668; 95%CI: 1.276-5.578). Kaplan-Meier analysis and Cox regression analysis showed that the longer time interval (> 9 wk) was a significant independent prognostic factor for DFS (P = 0.032; OR = 2.295; 95%CI: 1.074-4.905), but the time interval was not an independent prognostic factor for overall survival (P > 0.05). CONCLUSION: A longer time interval to surgery after neoadjuvant therapy may improve the pCR rate and DFS but has little impact on postoperative complications and sphincter preservation.

Selective lateral lymph node dissection after neoadjuvant chemoradiotherapy in rectal cancer.

BACKGROUND: Lateral lymph node metastasis is one of the leading causes of local recurrence in patients with advanced mid or low rectal cancer. Neoadjuvant chemoradiotherapy (NCRT) can effectively reduce the postoperative recurrence rate; thus, NCRT with total mesorectal excision (TME) is the most widely accepted standard of care for rectal cancer. The addition of lateral lymph node dissection (LLND) after NCRT remains a controversial topic. AIM: To investigate the surgical outcomes of TME plus LLND, and the possible risk factors for lateral lymph node metastasis after NCRT. METHODS: This retrospective study reviewed 89 consecutive patients with clinical stage II-III mid or low rectal cancer who underwent TME and LLND from June 2016 to October 2018. In the NCRT group, TME plus LLND was performed in patients with short axis (SA) of the lateral lymph node greater than 5 mm. In the non-NCRT group, TME plus LLND was performed in patients with SA of the lateral lymph node greater than 10 mm. Data regarding patient demographics, clinical workup, surgical procedure, complications, and outcomes were collected. Multivariate logistic regression analysis was performed to evaluate the possible risk factors for lateral lymph node metastasis in NCRT patients. RESULTS: LLN metastasis was pathologically confirmed in 35 patients (39.3%): 26 (41.3%) in the NCRT group and 9 (34.6%) in the non-NCRT group. The most common site of metastasis was around the obturator nerve (21/35) followed by the internal iliac artery region (12/35). In the NCRT patients, 46% of patients with SA of LLN greater than 7 mm were positive. The postoperative 30-d mortality rate was 0%. Two (2.2%) patients suffered from lateral local recurrence in the 2-year follow up. Multivariate analysis showed that cT4 stage (odds ratio [OR] = 5.124, 95% confidence interval [CI]: 1.419-18.508; P = 0.013), poor differentiation type (OR = 4.014, 95%CI: 1.038-15.520; P = 0.044), and SA ≥ 7 mm (OR = 7.539, 95%CI: 1.487-38.214; P = 0.015) were statistically significant risk factors associated with LLN metastasis. CONCLUSION: NCRT is not sufficient as a stand-alone therapy to eradicate LLN metastasis in lower rectal cancer patients and surgeons should consider performing selective LLND in patients with greater LLN SA diameter, poorer histological differentiation, or advanced T stage. Selective LLND for NCRT patients can have a favorable oncological outcome.

Corrigendum: Differential Expression Analysis Revealing CLCA1 to Be a Prognostic and Diagnostic Biomarker for Colorectal Cancer.

[This corrects the article DOI: 10.3389/fonc.2020.573295.].

Impact factors of lymph node retrieval on survival in locally advanced rectal cancer with neoadjuvant therapy.

BACKGROUND: Conventional clinical guidelines recommend that at least 12 lymph nodes should be removed during radical rectal cancer surgery to achieve accurate staging. The current application of neoadjuvant therapy has changed the number of lymph node dissection. AIM: To investigate factors affecting the number of lymph nodes dissected after neoadjuvant chemoradiotherapy in locally advanced rectal cancer and to evaluate the relationship of the total number of retrieved lymph nodes (TLN) with disease-free survival (DFS) and overall survival (OS). METHODS: A total of 231 patients with locally advanced rectal cancer from 2015 to 2017 were included in this study. According to the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) classification system and the NCCN guidelines for rectal cancer, the patients were divided into two groups: group A (TLN ≥ 12, n = 177) and group B (TLN < 12, n = 54). Factors influencing lymph node retrieval were analyzed by univariate and binary logistic regression analysis. DFS and OS were evaluated by Kaplan-Meier curves and Cox regression models. RESULTS: The median number of lymph nodes dissected was 18 (range, 12-45) in group A and 8 (range, 2-11) in group B. The lymph node ratio (number of positive lymph nodes/total number of lymph nodes) (P = 0.039) and the interval between neoadjuvant therapy and radical surgery (P = 0.002) were independent factors of the TLN. However,TLN was not associated with sex, age, ASA score, clinical T or N stage, pathological T stage, tumor response grade (Dworak), downstaging, pathological complete response, radiotherapy dose, preoperative concurrent chemotherapy regimen, tumor distance from anal verge, multivisceral resection, preoperative carcinoembryonic antigen level, perineural invasion, intravascular tumor embolus or degree of differentiation. The pathological T stage (P < 0.001) and TLN (P < 0.001) were independent factors of DFS, and pathological T stage (P = 0.011) and perineural invasion (P = 0.002) were independent factors of OS. In addition, the risk of distant recurrence was greater for TLN < 12 (P = 0.009). CONCLUSION: A shorter interval to surgery after neoadjuvant chemoradiotherapy for rectal cancer under indications may cause increased number of lymph nodes harvested. Tumor shrinkage and more extensive lymph node retrieval may lead to a more favorable prognosis.

Nomograms and risk score models for predicting survival in rectal cancer patients with neoadjuvant therapy.

BACKGROUND: Colorectal cancer is a common digestive cancer worldwide. As a comprehensive treatment for locally advanced rectal cancer (LARC), neoadjuvant therapy (NT) has been increasingly used as the standard treatment for clinical stage II/III rectal cancer. However, few patients achieve a complete pathological response, and most patients require surgical resection and adjuvant therapy. Therefore, identifying risk factors and developing accurate models to predict the prognosis of LARC patients are of great clinical significance. AIM: To establish effective prognostic nomograms and risk score prediction models to predict overall survival (OS) and disease-free survival (DFS) for LARC treated with NT. METHODS: Nomograms and risk factor score prediction models were based on patients who received NT at the Cancer Hospital from 2015 to 2017. The least absolute shrinkage and selection operator regression model were utilized to screen for prognostic risk factors, which were validated by the Cox regression method. Assessment of the performance of the two prediction models was conducted using receiver operating characteristic curves, and that of the two nomograms was conducted by calculating the concordance index (C-index) and calibration curves. The results were validated in a cohort of 65 patients from 2015 to 2017. RESULTS: Seven features were significantly associated with OS and were included in the OS prediction nomogram and prediction model: Vascular_tumors_bolt, cancer nodules, yN, body mass index, matchmouth distance from the edge, nerve aggression and postoperative carcinoembryonic antigen. The nomogram showed good predictive value for OS, with a C-index of 0.91 (95%CI: 0.85, 0.97) and good calibration. In the validation cohort, the C-index was 0.69 (95%CI: 0.53, 0.84). The risk factor prediction model showed good predictive value. The areas under the curve for 3- and 5-year survival were 0.811 and 0.782. The nomogram for predicting DFS included ypTNM and nerve aggression and showed good calibration and a C-index of 0.77 (95%CI: 0.69, 0.85). In the validation cohort, the C-index was 0.71 (95%CI: 0.61, 0.81). The prediction model for DFS also had good predictive value, with an AUC for 3-year survival of 0.784 and an AUC for 5-year survival of 0.754. CONCLUSION: We established accurate nomograms and prediction models for predicting OS and DFS in patients with LARC after undergoing NT.

Intraoperative intraperitoneal chemotherapy increases the incidence of anastomotic leakage after anterior resection of rectal tumors.

BACKGROUND: Intraoperative intraperitoneal chemotherapy is an emerging treatment modality for locally advanced rectal neoplasms. However, its impacts on postoperative complications remain unknown. Anastomotic leakage (AL) is one of the most common and serious complications associated with the anterior resection of rectal tumors. Therefore, we designed this study to determine the effects of intraoperative intraperitoneal chemotherapy on AL. AIM: To investigate whether intraoperative intraperitoneal chemotherapy increases the incidence of AL after the anterior resection of rectal neoplasms. METHODS: This retrospective cohort study collected information from 477 consecutive patients who underwent an anterior resection of rectal carcinoma using the double stapling technique at our institution from September 2016 to September 2017. Based on the administration of intraoperative intraperitoneal chemotherapy or not, the patients were divided into a chemotherapy group (171 cases with intraperitoneal implantation of chemotherapy agents during the operation) or a control group (306 cases without intraoperative intraperitoneal chemotherapy). Clinicopathologic features, intraoperative treatment, and postoperative complications were recorded and analyzed to determine the effects of intraoperative intraperitoneal chemotherapy on the incidence of AL. The clinical outcomes of the two groups were also compared through survival analysis. RESULTS: The univariate analysis showed a significantly higher incidence of AL in the patients who received intraoperative intraperitoneal chemotherapy, with 13 (7.6%) cases in the chemotherapy group and 5 (1.6%) cases in the control group (P = 0.001). As for the severity of AL, the AL patients who underwent intraoperative intraperitoneal chemotherapy tended to be more severe cases, and 12 (92.3%) out of 13 AL patients in the chemotherapy group and 2 (40.0%) out of 5 AL patients in the control group required a secondary operation (P = 0.044). A multivariate analysis was subsequently performed to adjust for the confounding factors and also showed that intraoperative intraperitoneal chemotherapy increased the incidence of AL (odds ratio = 5.386; 95%CI: 1.808-16.042; P = 0.002). However, the survival analysis demonstrated that intraoperative intraperitoneal chemotherapy could also improve the disease-free survival rates for patients with locally advanced rectal cancer. CONCLUSION: Intraoperative intraperitoneal chemotherapy can improve the prognosis of patients with locally advanced rectal carcinoma, but it also increases the risk of AL following the anterior resection of rectal neoplasms.

Analysis of 72 patients with colorectal high-grade neuroendocrine neoplasms from three Chinese hospitals.

BACKGROUND: Colorectal high-grade neuroendocrine neoplasms (HGNENs) are rare and constitute less than 1% of all colorectal malignancies. Based on their morphological differentiation and proliferation identity, these neoplasms present heterogeneous clinicopathologic features. Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial. AIM: To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy. METHODS: This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019. The clinicopathologic characteristics and follow-up data were carefully collected from their medical records, outpatient reexaminations, and telephone interviews. A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease. RESULTS: According to the latest recommendations for the classification and nomenclature of colorectal HGNENs, 61 (84.7%) patients in our cohort had poorly differentiated neoplasms, which were categorized as high-grade neuroendocrine carcinomas (HGNECs), and the remaining 11 (15.3%) patients had well differentiated neoplasms, which were categorized as high-grade neuroendocrine tumors (HGNETs). Most of the neoplasms (63.9%) were located at the rectum. More than half of the patients (51.4%) presented with distant metastasis at the date of diagnosis. All patients were followed for a median duration of 15.5 mo. In the entire cohort, the median survival time was 31 mo, and the 3-year and 5-year survival rates were 44.3% and 36.3%, respectively. Both the univariate and multivariate analyses demonstrated that increasing age, HGNEC type, and distant metastasis were risk factors for poor clinical outcomes. CONCLUSION: Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes. However, patients with younger age, good morphological differentiation, and without metastatic disease can have a relatively favorable prognosis.