Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.
Humans ; Pyroptosis ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Gasdermins ; Chemoradiotherapy/adverse effects* ; Rectal Neoplasms/surgery* ; Caspases/metabolism* ; Diarrhea/chemically induced* ; Leukopenia/genetics* ; Genetic Variation ; Dermatitis

Objective: To investigate the causes and management of long-term persistent pelvic presacral space infection. Methods: Clinical data of 10 patients with persistent presacral infection admitted to the Cancer Hospital of Zhengzhou University from October 2015 to October 2020 were collected. Different surgical approaches were used to treat the presacral infection according to the patients' initial surgical procedures. Results: Among the 10 patients, there were 2 cases of presacral recurrent infection due to rectal leak after radiotherapy for cervical cancer, 3 cases of presacral recurrent infection due to rectal leak after radiotherapy for rectal cancer Dixons, and 5 cases of presacral recurrent infection of sinus tract after adjuvant radiotherapy for rectal cancer Miles. Of the 5 patients with leaky bowel, 4 had complete resection of the ruptured nonfunctional bowel and complete debridement of the presacral infection using an anterior transverse sacral incision with a large tipped omentum filling the presacral space; 1 had continuous drainage of the anal canal and complete debridement of the presacral infection using an anterior transverse sacral incision. 5 post-Miles patients all had debridement of the presacral infection using an anterior transverse sacral incision combined with an abdominal incision. The nine patients with healed presacral infection recovered from surgery in 26 to 210 days, with a median time of 55 days. Conclusions: Anterior sacral infections in patients with leaky gut are caused by residual bowel secretion of intestinal fluid into the anterior sacral space, and in post-Miles patients by residual anterior sacral foreign bodies. An anterior sacral caudal transverse arc incision combined with an abdominal incision is an effective surgical approach for complete debridement of anterior sacral recalcitrant infections.
Humans ; Reinfection ; Rectum/surgery* ; Rectal Neoplasms/surgery* ; Drainage ; Anal Canal/surgery* ; Pelvic Infection

Pelvic exenteration is often required for primary rectal cancer beyond total mesorectal excision (PRC-bTME) and locally recurrent rectal cancer (LRRC). Some patients with radical resection can achieve long-term survival, but they need to face risks, such as huge surgical trauma, serious perioperative complications, permanent loss of organ function and decline in quality of life. Preoperative evaluation of PRC-bTME and LRRC should emphasize multidisciplinary collaboration, and develop individualized diagnosis and treatment strategies. The principles of function preservation and risk-benefit balance in surgery oncology should be followed, and R0 resection should be emphasized. Perioperative complications, surgical trauma and organ function loss should be minimized to achieve the best quality control and balance point. This consensus was formulated by the Colorectal Cancer Committee of the Chinese Medical Doctor Association and the Gastrointestinal Surgery Committee of China International Exchange and Promotive Association for Medical and Health Care. The draft was formed based on the summary of domestic and foreign research progress and expert experience. After discussion, review and modification by experts, an anonymous voting was conducted for each major opinion, and in-depth verification was carried out according to the principles of evidence-based medicine. Finally, the Chinese expert consensus on the pelvic exenteration with primary rectal cancer beyond total mesorectal excision planes and locally recurrent rectal cancer (2023 edition) was formed. This consensus mainly summarizes the indications and contraindications of PE for PRC-bTME and LRRC, preoperative diagnosis and evaluation, perioperative treatment, as well as the resection scope, surgical methods, reconstruction of related organs, safety and complications of PE, postoperative follow-up and other issues, in order to provide guidance for PE in patients with PRC-bTME and LRRC.
Humans ; Consensus ; Neoplasm Recurrence, Local/surgery* ; Pelvic Exenteration ; Quality of Life ; Rectal Neoplasms/surgery* ; Treatment Outcome ; China

After the implementation of neoadjuvant chemoradiotherapy and total mesorectal excision, lateral local recurrence becomes the major type of local recurrence after surgery in rectal cancer. Most lateral recurrence develops from enlarged lateral lymph nodes on an initial imaging study. Evidence is accumulating to support the combined use of neoadjuvant chemoradiotherapy and lateral lymph node dissection. The accuracy of diagnosing lateral lymph node metastasis remains poor. The size of lateral lymph nodes is still the most commonly used variable with the most consistent accuracy and the cut-off value ranging from 5 to 8 mm on short axis. The morphological features, differentiation of the primary tumor, circumferential margin, extramural venous invasion, and response to chemoradiotherapy are among other risk factors to predict lateral lymph node metastasis. Planning multiple disciplinary treatment strategies for patients with suspected nodes must consider both the risk of local recurrence and distant metastasis. Total neoadjuvant chemoradiotherapy is the most promising regimen for patients with a high risk of recurrence. Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy seemingly improves the local control of positive lateral nodes. However, its impact on the safety of surgery in patients with no response to the treatment or regrowth of lateral nodes remains unclear. For patients with smaller nodes below the cut-off value or shrunken nodes after treatment, a close follow-up strategy must be performed to detect the recurrence early and perform a salvage surgery. For patients with stratified lateral lymph node metastasis risks, plans containing different multiple disciplinary treatments must be carefully designed for long-term survival and better quality of life.
Humans ; Lymphatic Metastasis/pathology* ; Quality of Life ; Neoplasm Staging ; Retrospective Studies ; Lymph Nodes/pathology* ; Rectal Neoplasms/surgery* ; Lymph Node Excision/methods* ; Neoadjuvant Therapy/methods* ; Neoplasm Recurrence, Local/surgery*

Colorectal cancer is one of the most common cancers in the world, and surgery is the mainstage treatment. Urogenital and sexual dysfunction after radical resection of rectal cancer has become an important problem for patients, which seriously affects the quality of life. Some patients give up radical surgery for rectal cancer because of the concerns about sexual and urinary dysfunction. The cause of this problem is intraoperative of injury pelvic autonomic nerve. The preservation of the hypogastric nerve during the surgery is important for the male ejaculation. Pelvic splanchnic nerves are mainly responsible for the male erection. The anatomical origin, distribution, and urogenital function of these two nerves are detailed described in this article. At the same time, this article introduces the classification, key points of the operation and the evaluation of autonomic nerve preservation surgery. With the rapid development of minimally invasive surgery, performing radical surgery for rectal cancer is important, we also need to fully understand the anatomical concept of pelvic autonomic nerves, and apply modern minimally invasive surgical techniques to preserve the patient's pelvic autonomic nerves as well. It is an compulsory course and an important manifestation for the standardization of rectal cancer surgery.
Humans ; Male ; Clinical Relevance ; Quality of Life ; Autonomic Pathways/surgery* ; Rectal Neoplasms/surgery* ; Pelvis/innervation*

Objective: To investigate the factors influencing tumor-specific survival of early-onset locally advanced rectal cancer. Methods: All-age patients with primary locally advanced rectal cancer from the Surveillance, Epidemiology, and End Results (SEER) database (2010 to 2019) were included in this study. Early- and late-onset locally advanced rectal cancer was defined according to age of 50 years at diagnosis. Early-onset locally advanced rectal cancer was divided into five age groups for subgroup analyses. Age, sex, tumor-specific survival time and survival status of patients at diagnosis, pathological grade, TNM stage, perineural invasion, tumor deposits, tumor size, pretreatment CEA , radiotherapy, chemotherapy, and number of lymph node dissections were included. Progression-free survival (PFS) was analyzed and compared between patients with early- and late-onset rectal cancer. Results: A total of 5,048 patients with locally advanced rectal cancer were included in the study (aged 27-70 years): 1,290 (25.55%) patients with early-onset rectal cancer and 3,758 (74.45%) patients with late-onset rectal cancer. Patients with early-onset rectal cancer had a higher rate of perineural invasion (P<0.001), more positive lymph nodes dissected (P<0.001), higher positive lymph node ratios (P<0.001), and a higher proportion receiving preoperative radiotherapy (P=0.002). Patients with early-onset rectal cancer had slightly better short-term survival than those with late-onset rectal cancer (median (IQR ): 54 (33-83) vs 50 (31-79) months, χ²=5.192, P=0.023). Multivariate Cox regression for all patients with locally advanced rectal cancer showed that age (P=0.008), grade of tumor differentiation (P=0.002), pretreatment CEA (P=0.008), perineural invasion (P=0.021), positive number (P=0.004) and positive ratio (P=0.001) of dissected lymph nodes, and sequence of surgery and radiotherapy (P=0.005) influenced PFS. This suggests that the Cox regression results for all patients may not be applicable to patients with early-onset cancer. Cox analysis showed tumor differentiation grade (patients with low differentiation had a higher risk of death, P=0.027), TNM stage (stage III patients had a higher risk of death, P=0.025), T stage (higher risk of death in stage T4, P<0.001), pretreatment CEA (P=0.002), perineural invasion (P<0.001), tumor deposits (P=0.005), number of dissected lymph nodes (patients with removal of 12-20 lymph nodes had a lower risk of death, P<0.001), and positive number of dissected lymph nodes (P<0.001) were independent factors influencing PFS of patients with early-onset locally advanced rectal cancer. Conclusion: Patients with early-onset locally advanced rectal cancer were more likely to have adverse prognostic factors, but an adequate number of lymph node dissections (12-20) resulted in better survival outcomes.
Humans ; Prognosis ; Retrospective Studies ; Neoplasm Staging ; Extranodal Extension/pathology* ; Survival Analysis ; Rectal Neoplasms/surgery* ; Lymph Nodes/pathology*

In recent years, with advances in pelvic oncology and surgical techniques, surgeons have redefined the boundaries of pelvic surgery. Combined pelvic exenteration is now considered the treatment of choice for some patients with locally advanced and locally recurrent rectal cancer, but it is only performed in a few hospitals in China due to the complexity of the procedure and the large extent of resection, complications, and high perioperative mortality. Although there have been great advances in oncologic drugs and surgical techniques and equipment in recent years, there are still many controversies and challenges in the preoperative assessment of combined pelvic organ resection, neoadjuvant treatment selection and perioperative treatment strategies. Adequate understanding of the anatomical features of the pelvic organs, close collaboration of the clinical multidisciplinary team, objective assessment and standardized preoperative combination therapy creates the conditions for radical surgical resection of recurrent and complex locally advanced rectal cancer, while the need for rational and standardized R0 resection still has the potential to bring new hope to patients with locally advanced and recurrent rectal cancer.
Humans ; Pelvic Exenteration/methods* ; Neoplasm Recurrence, Local/surgery* ; Rectum/surgery* ; Rectal Neoplasms/surgery* ; Pelvis/surgery* ; Treatment Outcome ; Retrospective Studies

The China PelvEx Collaborative, under the direction of Colorectal Cancer Committee of the Chinese Medical Doctor Association, Gastrointestinal Surgery Committee of China International Exchange and Promotive Association for Medical and Health, has formulated and issued the Chinese expert consensus for primary rectal cancer beyond total mesorectal excision planes and locally recurrent rectal cancer (2023 edition) , with the academic support of the Chinese Journal of Gastrointestinal Surgery and Chinese Journal of Colorectal Disease (Electronic Edition). This Consensus refers to the expert consensus developed by the International PelvEx Collaboration, incorporates the latest international multi-center research results and combines the latest research results in China. The Consensus unifies some definitions, clarifies the surgical indications, and puts forward the definition and preventive measures of "empty pelvic syndrome" earlier. For the controversial classification of local recurrent rectal cancer, the Chinese classification was proposed for the first time in Consensus. At the same time, the definition of pelvic exenteration is controversial, and a more consistent cognition is proposed. It is believed that, with the in-depth research on complicated rectal cancer, C-PelvEx will gather more higher-level data from clinical research in several domestic centers, so as to further enrich the content of the updated Consensus.
Humans ; Consensus ; Neoplasm Recurrence, Local/surgery* ; Pelvic Exenteration ; Rectal Neoplasms/surgery*

The treatment of locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC) has been a difficulty and challenge in the field of advanced rectal cancer, while pelvic exenteration (PE), as an important way to potentially achieve radical treatment of LARC and LRRC, has been shown to significantly improve the long-term prognosis of patients. The implementation of PE surgery requires precise assessment of the extent of invasion of LARC or LRRC and adequate preoperative preparation through multidisciplinary consultation before surgery. The lateral pelvis involves numerous tissues, blood vessels, and nerves, and resection is most difficult, and the ureteral and Marcille triangle approaches are recommended; while the supine transabdominal approach combined with intraoperative change to the prone jacket position facilitates adequate exposure of the surgical field and enables precise overall resection of the bony pelvis and pelvic floor muscle groups invaded by the tumor. Empty pelvic syndrome has always been an major problem to be solved during PE. The application of extracellular matrix biological mesh to reconstruct pelvic floor defects and isolate the abdominopelvic cavity is expected to reduce postoperative pelvic floor related complications. Reconstruction of the urinary system and important vessels after PE is essential, and the selection of appropriate reconstruction methods helps to improve the patient's postoperative quality of life, while more new methods are also being continuously explored.
Humans ; Pelvic Exenteration/adverse effects* ; Quality of Life ; Neoplasm Recurrence, Local/surgery* ; Pelvis/pathology* ; Postoperative Complications/etiology* ; Rectal Neoplasms/pathology* ; Retrospective Studies ; Treatment Outcome

Objective: To explore the feasibility, safety, and short- and long-term efficacy of laparoscopic pelvic exenteration (LPE) in treating locally advanced rectal cancer. Methods: The clinical data of 173 patients who had undergone pelvic exenteration (PE) for locally advanced rectal cancer that had been shown by preoperative imaging or intraoperative exploration to have invaded beyond the mesorectal excision plane and adjacent organs in the Cancer Hospital, Chinese Academy of Medical Sciences (n=64) and Peking University First Hospital (n=109) from 2010 January to 2021 December were collected retrospectively. Laparoscopic PE (LPE) had been performed on 82 of these patients and open PE (OPE) on 91. Short- and long-term outcomes (1-, 3-, and 5-year overall and disease-free survival and 1- and 3-year cumulative local recurrence rates) were compared between these groups. Results: The only statistically significant difference in baseline data between the two groups (P>0.05) was administration of neoadjuvant therapy. Compared with OPE, LPE had a significantly shorter operative time (319.3±129.3 minutes versus 417.3±155.0 minutes, t=4.531, P<0.001) and less intraoperative blood loss (175 [20-2000] ml vs. 500 [20-4500] ml, U=2206.500, P<0.001). The R0 resection rates were 98.8% and 94.5%, respectively (χ²=2.355, P=0.214). At 18.3% (15/82), and the incidence of perioperative complications was lower in the LPE group than in the OPE group (37.4% [34/91], χ²=7.727, P=0.005). The rates of surgical site infection were 7.3% (6/82) and 23.1% (21/91) in the LPE and OPE group, respectively (χ²=8.134, P=0.004). The rates of abdominal wound infection were 0 and 12.1% (11/91) (χ²=10.585, P=0.001), respectively, and of urinary tract infection 0 and 6.6% (6/91) (χ²=5.601, P=0.030), respectively. Postoperative hospital stay was shorter in the LPE than OPE group (12 [4-60] days vs. 15 [7-87] days, U=2498.000, P<0.001). The median follow-up time was 40 (2-88) months in the LPE group and 59 (1-130) months in the OPE group. The 1-, 3-, and 5-year overall survival rates were 91.3%, 76.0%, and 62.5%, respectively, in the LPE group, and 91.2%, 68.9%, and 57.6%, respectively, in the OPE group. The 1, 3, and 5-year disease-free survival rates were 82.8%, 64.9%, and 59.7%, respectively, in the LPE group and 76.9%, 57.8%, and 52.7%, respectively, in the OPE group. The 1- and 3-year cumulative local recurrence rates were 5.1% and 14.1%, respectively, in the LPE group and 8.0% and 15.1%, respectively, in the OPE group (both P>0.05). Conclusions: In locally advanced rectal cancer patients, LPE is associated with shorter operative time, less intraoperative blood loss, fewer perioperative complications, and shorter hospital stay compared with OPE. It is safe and feasible without compromising oncological effect.
Humans ; Pelvic Exenteration/methods* ; Retrospective Studies ; Treatment Outcome ; Blood Loss, Surgical ; Laparoscopy/methods* ; Rectal Neoplasms/surgery*