Recognition of empty pelvic syndrome and its prevention and treatment / 中华胃肠外科杂志

With the development of existing surgical techniques, equipment and treatment concepts, more and more medical centers begin to carry out extensive resection for recurrent pelvic malignant tumors or those with multivisceral invasion. Exenteration may facilitate curative resection and improve the outcome of the patients. Therefore, pelvic exenteration has gradually become the standard of care for locally advanced pelvic malignancies. At present, pelvic exenteration leads to high intraoperative and postoperative complications and mortality, and therefore compromise the safety and long-term quality of life. Cumulating evidences suggest remnant cavity after exenteration might trigger the pathophysiological process and cause downstream complications which can be defined as empty pelvis syndrome. The literature related to empty pelvic syndrome was summarized, the possible cause of empty pelvic syndrome was analyzed. After the pelvic exenteration, the closed pelvic residual cavity formed continuous negative pressure with the gradual absorption of air in the cavity, bacterial propagation, and accumulation of fluid, which had an impact on the distribution of organs in the abdominal and pelvic cavity. At the same time, whether physical processes also play a role in the occurrence of empty pelvic syndrome remains to be explored. It is concluded that the diagnosis is mainly based on the patient's medical history, clinical manifestations and radiological findings, and the history of pelvic exenteration is the most important indicator in the diagnosis. In terms of prevention measures, we should identify the high-risk groups of the occurrence of empty pelvic syndrome, and then take accurate and individualized preventive measures. Various new biomaterials have more advantages in preventive pelvic cavity filling than traditional human tissue filling. Mesentery plays an important role in the morphology, peristalsis and arrangement of the small intestine. More attention should be paid to reducing the ectopic placement of the small intestine into the pelvic cavity by protecting the mesentery structure and restoring or rebuilding the mesentery morphology. In terms of treatment measures, there is still a lack of standard treatment pathway for empty pelvic syndrome.

Analysis of prognosis and influencing factors of No. 253 lymph node metastasis in descending colon, sigmoid colon, and rectal cancer: a multicenter study / 中华外科杂志

Objectives: To analyze the influencing factors of No. 253 lymph node metastasis in descending colon cancer, sigmoid colon cancer, and rectal cancer, and to investigate the prognosis of No. 253 lymph node-positive patients by propensity score matching analysis. Methods: A retrospective analysis was performed on clinical data from patients with descending colon cancer, sigmoid colon cancer, rectosigmoid junction cancer, and rectal cancer who underwent surgery between January 2015 and December 2019 from the Cancer Hospital of the Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Peking Union Medical College Hospital, General Hospital of the Chinese People's Liberation Army, and Peking University Cancer Hospital. A total of 3 016 patients were included according to inclusion and exclusion criteria, comprising 1 848 males and 1 168 females, with 1 675 patients aged≥60 years and 1 341 patients aged<60 years. Clinical and pathological factors from single center data were subjected to univariate analysis to determine influencing factors of No. 253 lymph node metastasis, using a binary Logistic regression model. Based on the results of the multivariate analysis, a nomogram was constructed. External validation was performed using data from other multicenter sources, evaluating the effectiveness through the area under the receiver operating characteristic curve and the calibration curve. Using data from a single center, the No. 253 lymph node-positive group was matched with the negative group in a 1∶2 ratio (caliper value=0.05). Survival analysis was performed using the Kaplan-Meier method and Log-rank test. The Cox proportional hazards model was used to determine independent prognostic factors. Results: (1) The tumor diameter≥5 cm (OR=4.496,95%CI:1.344 to 15.035, P=0.015) T stage (T4 vs. T1: OR=11.284, 95%CI:7.122 to 15.646, P<0.01), N stage (N2 vs. N0: OR=60.554, 95%CI:7.813 to 469.055, P=0.043), tumor differentiation (moderate vs. well differentiated: OR=1.044, 95%CI:1.009 to 1.203, P=0.044; poor vs. well differentiated: OR=1.013, 95%CI:1.002 to 1.081, P=0.013), tumor location (sigmoid colon vs. descending colon: OR=9.307, 95%CI:2.236 to 38.740, P=0.002), pathological type (mucinous adenocarcinoma vs. adenocarcinoma: OR=79.923, 95%CI:15.113 to 422.654, P<0.01; signet ring cell carcinoma vs. adenocarcinoma: OR=27.309, 95%CI:4.191 to 177.944, P<0.01), and positive vascular invasion (OR=3.490, 95%CI:1.033 to 11.793, P=0.044) were independent influencing factors of No. 253 lymph node metastasis. (2) The area under the curve of the nomogram prediction model was 0.912 (95%CI: 0.869 to 0.955) for the training set and 0.921 (95%CI: 0.903 to 0.937) for the external validation set. The calibration curve demonstrated good consistency between the predicted outcomes and the actual observations. (3) After propensity score matching, the No. 253 lymph node-negative group did not reach the median overall survival time, while the positive group had a median overall survival of 20 months. The 1-, 3- and 5-year overall survival rates were 83.9%, 61.3% and 51.6% in the negative group, and 63.2%, 36.8% and 15.8% in the positive group, respectively. Multivariate Cox analysis revealed that the T4 stage (HR=3.067, 95%CI: 2.357 to 3.990, P<0.01), the N2 stage (HR=1.221, 95%CI: 0.979 to 1.523, P=0.043), and No. 253 lymph node positivity (HR=2.902, 95%CI:1.987 to 4.237, P<0.01) were independent adverse prognostic factors. Conclusions: Tumor diameter ≥5 cm, T4 stage, N2 stage, tumor location in the sigmoid colon, adverse pathological type, poor differentiation, and vascular invasion are influencing factors of No. 253 lymph node metastasis. No. 253 lymph node positivity indicates a poorer prognosis. Therefore, strict dissection for No. 253 lymph node should be performed for colorectal cancer patients with these high-risk factors.

A prediction model of pathological complete response in patients with locally advanced rectal cancer after PD-1 antibody combined with total neoadjuvant chemoradiotherapy based on MRI radiomics / 中华胃肠外科杂志

Objective: To construct a prediction model of pathologic complete response (pCR) in locally advanced rectal cancer patients who received programmed cell death protein-1 (PD-1) antibody and total neoadjuvant chemoradiotherapy by using radiomics based on MR imaging data and to investigate its predictive value. Methods: A clinical diagnostic test study was carried out. Clinicopathalogical and radiological data of 38 patients with middle-low rectal cancer who received PD-1 antibody combined with total neoadjuvant chemoradiotherapy and underwent TME surgery from January 2019 to September 2021 in our hospital were retrospectively collected. Among 38 patients, 23 were males and 15 were females with a median age of 68 (47-79) years and 13 (34.2%) a chieved pCR. These 38 patients were stratified and randomly divided into the training group (n=26) and test group (n=12) for modeling. All the patients underwent rectal MRI before treatment. The clinical, imaging and radiomics features of all the patients were collected, and the clinical feature model and radiomics model were constructed. The receiver operating characteristic (ROC) curves of each model were drawn, and the constructed model was evaluated through the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: There were no significant differences in age, gender, primary location of tumor and postoperative pathology between the two groups (all P>0.05). Forty-one features were extracted from region of interest in each modality, including 9 first-order features, 24 gray level co-occurrence matrix features and 8 shape features. From 38 patients, 41 features were extracted from each imaging modality of baseline and preoperative DWI and T2WI images, totally 164 features. Only 4 features were preserved after correlation analysis between each pair of features and t-test between pCR and non-pCR subjects. After LASSO cross validation, only the first-order skewness of the baseline DWI image before treatment and the volume in the baseline T2WI image before treatment were retained. The area under the curve, sensitivity, specificity, positive and negative predictive values of the prediction model established by applying these two features in the training group and the test group were 0.856 and 0.844, 77.8% and 100.0%, 88.2% and 75.0%, 77.8% and 66.7%, 88.2% and 100.0%, respectively. The decision curve analysis of the radiomics model showed that the strategy of this model in predicting pCR was better than that in treating all the patients as pCR and that in treating all the patients as non-pCR. Conclusion: The pCR prediction model for rectal cancer patients receiving PD-1 antibody combined with total neoadjuvant radiochemotherapy based on MRI radiomics has the potential to be used in clinical screening or rectal cancer patients who can be spared from radical surgery.

Multicenter real-world study on safety and efficacy of neoadjuvant therapy in combination with immunotherapy for colorectal cancer / 中华胃肠外科杂志

Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.

Current status, controversy and challenge in the neoadjuvant immunotherapy of colorectal cancer / 中华胃肠外科杂志

Neoadjuvant therapy for colorectal cancer is widely used in rectal cancer, locally advanced colon cancer, and resectable metastatic and recurrent colorectal cancer. Mismatch repair deficient(dMMR) and microsatellite instablity-high (MSI-H) colorectal cancer patients who benefit from the efficacy of immune checkpoint inhibitors are expected to further improve the efficacy of traditional neoadjuvant therapy based on radiotherapy and chemotherapy. In this paper, the current status of immunotherapy (with emphasis on immune checkpoint inhibitors) is elucidated, and the opportunities of its application in neoadjuvant therapy are analyzed, including poor sensitivity of dMMR tumors to traditional therapy, good immune response of early tumors, predictable, manageable and controllable toxicity of immune checkpoint inhibitors. Colorectal cancer patients have growing and diverse needs to be met. Current controversies and challenges are analyzed, and the future directions are pointed out, including active screening of benefit groups, exploration of efficacy prediction markers, optimization of neoadjuvant immunotherapy models, attention to efficacy evaluation and new therapeutic endpoints. Neoadjuvant therapy should be effective, moderate and accurate based on the treatment target. It is the prerequisite and basis to guarantee medical safety and improve therapeutic effect to attach importance to the standardization and safety of clinical research and to pay attention to patients' interests and legal and ethical demands.

Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors / 中华胃肠外科杂志

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.

Questionnaire investigation of radiation rectal injury with anxiety, depression and somatic disorder / 中华胃肠外科杂志

Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.

Role of multidisciplinary cooperation in the diagnosis and treatment of pelvic floor disorder disease / 中华胃肠外科杂志

The pelvic floor disorder disease (PFDD) typically originates from supportive tissue defects or injuries in the pelvic floor with a wide spectrum of symptoms such as urinary incontinence, pelvic organ prolapse, sexual dysfunction, fecal incontinence and chronic pelvic pain. But its etiology is complex, involving multiple systems and organs. So the best management of PFDD requires the implementation of multidisciplinary team (MDT). Pelvic floor centers have been developed abroad to provide pelvic floor services. In the setting of PFDD, the concept of MDT starts lately and develops slowly in China. The MDT approach was demonstrated to improve general rehabilitation, psychological state and quality of life. However, there is no unified standardization for MDT diagnosis and treatment of PFDD at home and abroad. Meanwhile, the personnel composition, responsibilities, training, and operation mode of the MDT need to be further developed. Perfecting the management mode of MDT team members, establishing standardized training programs and assessment criteria play crucial role in the future development of MDT in PFDD.

Organoid in colorectal cancer: progress and challenges / 中华医学杂志(英文版)

Patient-derived tumor organoids (PDOs) currently represent important modeling tools in pre-clinical investigation of malignancies. Organoid cultures conserve the genetic and phenotypic characteristics of the original tumor and maintain its heterogeneity, allowing their application in many research fields. PDOs derived from colorectal cancer (CRC) have been used for genetic modeling to investigate the function of driver genes. Some researchers have been exploring the value of CRC PDOs in chemotherapy, targeted therapy, and radiotherapy response prediction. The successful generation of PDOs derived from CRC could deepen our understanding of CRC biology and provide novel tools for cancer modeling, for realizing precision medicine by assessing specimens from individual patients ex vivo. The present review discusses recently reported advances in CRC PDOs and the challenges they face as pre-clinical models in CRC research.

Retrospective analysis of 19 cases with middle-to-low rectal cancer who underwent local excision following neoadjuvant chemoradiation / 中国实用外科杂志

OBJECTIVE: To investigate the prognosis and quality of life of patients who underwent transanal local excision(LE) following neoadjuvant chemoradiation for mid-low rectal cancer.METHODS: Patients undergo neoadjuvant chemoradiaiton and transanal local excision from March 2011 to June 2016 in Gastrointestinal cancer center,Peking University Cancer Hospital were enrolled in this study. Data of 19 cases were retrospectively collected and analyzed. The primary end points were disease free survival,short-term(1 month)postoperative complications; and secondary endpoints were quality of life and anal function one year after the surgery.RESULTS: Median tumor diameter was 1.0(0.3-3.0)cm. 8(42.1%) cases located in the anterior wall,6 cases(31.6%) in the posterior wall,3 cases(15.8%) in the left wall,and 2 cases(10.5%) in the right wall. The median distance of the tumor from the anal verge was 4.0(1.5-12.0)cm. Postoperative pathology demonstrated that 12 cases(63.2%) ypT0,3 cases(15.8%) ypT1,4 cases(21.1%) ypT2;the median time interval between chemoradiotherapy and LE was 4.3(2.0-36.0)months;The median time of operation was 50(20-137)min,with median blood loss 10(0-50)ml and hospital stay 4(1-5)d. The recurrence rate was 21.1%(1 local recurrence, 2 lung metastasis, 1 pelvic metastasis) with a follow up of 30(2-62) months.TME group had worse quality of life and anal function following TME surgery(P<0.01) while LE group not. LE group has better quality of life(EORTC-C30) and anal function(Wexner) than TME group(P<0.01).CONCLUSION: For mid-low rectal cancer with good response(ycT0-2 N0) following neoadjuvant chemoradiation,local excision might be a safe and feasible treatment option with acceptable anal function anal function.

Surgical treatment of anorectal malignant melanoma from single tertiary center: A retrospective analysis of 91 cases / 中国实用外科杂志

OBJECTIVE:To investigate the surgical treatment of anorectal malignant melanoma(ARMM) and the prognostic factors that affect patients' overall survival(OS).METHODS:Theclinical and pathological data of 91 patients diagnosed as ARMM, who underwent surgery in the Gastrointestinal Cancer Center of Peking University Cancer Hospital from January 2003 to January 2018 were retrospectively analyzed. The effects of different clinicopathological factors on OS of the patients, and difference surgery, abdominal-perineal resection(APR) and wide local excision(WLE) on patients' survival were compared.RESULTS:Of the 91 patients with ARMM, 35(38.5%) were male, 56(61.5%) were female, and the ratio of male to female was 1:1.6. 12 patients(13.2%) underwent wide local excision and 79 patients underwent abdominal-perineal resection(86.8%); there were 19 cases(20.9%) diagnosed with distant metastasis and 72 cases(79.1%)without distant metastasis. The of 1-, 3-, and 5-year survival rates of ARMM patients in this cohort were 74%, 23% and9%; and the median survival of the patients was 18.7 months. The univariate analysis of the clinicopathological features of the patients demonstrated that the preoperative distant metastases, tumor diameters(>2 cm), tumor invasion depth(>2 mm) and lymph node metastasis were the prognostic factors of OS; multivariate analysis showed that preoperative distant metastasis and lymph node metastasis were independent factors affecting OS.The median survival of the patients admitted APR and WLE were both 21 months. There was no significant difference in survival between the WLE and APR group(P=0.94).CONCLUSION:Preoperative distant metastasis and lymph node metastasis are independent prognostic factors for overall survival of ARMM patients.Comparing with WLE, APR could not bring survival benefits.

Organoid Culture of Isolated Cells from Patient-derived Tissues with Colorectal Cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Colorectal cancer (CRC) is a heterogeneous disease; current research relies on cancer cell lines and animal cancer models, which may not precisely imitate inner human tumors and guide clinical medicine. The purpose of our study was to explore and further improve the process of producing three-dimensional (3D) organoid model and impel the development of personalized therapy.</p><p><b>METHODS</b>We subcutaneously injected surgically resected CRC tissues from a patient into BALB/c-nu mice to build patient-derived xenografts (PDXs). Isolated cells from PDXs at appropriate tumor size were mingled with Matrigel, and then seeded in ultra-low attachment 96-well plates at four cell densities (500, 1000, 2000, and 4000 single cells/well). Cells were cultured with advanced Dulbecco's Modified Eagle Medium/F12 medium additional with various factors added to maintain tumor's biological traits and growth activity. The growth curves of the four cell densities were measured after 24 h of culture until 25 days. We evaluated the effects of four chemotherapeutic agents on organoid model by the CellTiter-Glo ® Luminescent Cell Viability Assay. Hematoxylin and eosin (H and E) staining of 3D organoids was performed and compared with patient and CRC PDX tissues. Furthermore, immunohistochemistry was performed, in which the organoids were stained with the proliferation marker, Ki-67. During the experimental process, a phase-contrast microscope was used.</p><p><b>RESULTS</b>Phenotype experimental results showed that 3D organoids were tightly packed together and grew robustly over time. All four densities of cells formed organoids while that composed of 2000 cells/well provided an adequate cultivation system and grew approximately 8-fold at the 25 th day. The chemosensitivity of the four conventional drugs was [s]-10-hydroxycamptothecin > mitomycin C > adriamycin > paclitaxel, which can guide clinical treatment. Histological features of CRC patient's tumor tissues and mice tumor xenograft tissues were highly similar, with high-column-like epithelium and extracellular matrix. H and E-stained sections showed heterogeneous cell populations harbored in cancer organoids and were histologically similar to tumor tissues. The proliferation index was only 8.33% within spheroids, which exhibited confined proliferative cells that might be cancer stem cells.</p><p><b>CONCLUSIONS</b>We successfully constructed a CRC organoid model that grew robustly over 25 days and demonstrated that 2000 cells/well in 96-well plate was a prime seeding density for cells to form organoids. The results confirmed that organoid model can be used for agent screening and personalized medicine.</p>

Diagnosis and minimally invasive treatment of gastric remnant cancer / 中华胃肠外科杂志

Gastric remnant cancer (GRC) is defined as cancer in the remnant stomach after partial gastrectomy. The incidence of GRC is rising in recent years. The carcinogenesis, development, and metastasis of GRC are different from primary gastric cancer. The early detection of GRC should be based on rational surveillance of patients following gastrectomy. For early stage GRC, endoscopic resection is one of the safe and effective methods. For advanced GRC, the primary treatment alternative is surgical resection. Minimally invasive procedures such as laparoscopic exploration, laparoscopic-assisted resection of GRC are still safe choices for experienced surgeons.

Application of perioperative imatinib mesylate therapy in initial resectable primary local advanced gastrointestinal stromal tumor at intermediate or high risk / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of perioperative imatinib mesylate (IM) therapy for patients with initial resectable primary local advanced gastrointestinal stromal tumor (GIST) at intermediate or high risk on R0 resection rate and the prognosis.</p><p><b>METHODS</b>Forty-eight above GIST patients between December 2001 and February 2012 were divided into 2 groups: neoadjuvant group (15 cases, pre- and post-operation IM therapy) and adjuvant group (33 cases, post-operative IM therapy). R0 resection rate, complication rate, disease-free survival (DFS) and overall survival (OS) were analyzed and compared between the two groups.</p><p><b>RESULTS</b>The maximal tumor diameter and average tumor diameter were larger in neoadjuvant group as compared to adjuvant group (11.2 cm vs. 7.7 cm, P=0.005; 9.1 cm vs. 6.2 cm, P=0.014). The response rate of preoperative IM therapy was 93.3% (14/15). The R0 resection rate was 86.7% and 84.8% (P=1.000), and the complication rate was 13.3% and 9.1% (P=0.642) in neoadjuvant and adjuvant group respectively. The 3-year DFS was 55% and 41% (P=0.935), and 5-year OS was 83% and 75% (P=0.766) in neoadjuvant and adjuvant group respectively.</p><p><b>CONCLUSIONS</b>Resectable primary local advanced GIST at intermediate or high risk with larger tumor diameter receiving perioperative IM therapy can achieve the same R0 resection rate, complication rate, DFS and OS as the GIST with smaller diameter receiving operation first. Perioperative IM therapy has potential advantage.</p>

Analysis of risk factors for pulmonary metastasis after curative resection of colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the risk factors for pulmonary metastasis after curative resection of colorectal cancer in order to improve the effectiveness of follow-up and the rate of early diagnosis for the high-risk patients.</p><p><b>METHODS</b>The clinicopathological and follow-up data of 268 patients with colorectal cancer undergoing radical resection from January 2004 to December 2006 in the Beijing Cancer Hospital were analyzed retrospectively. Patients were divided into study group including 16(6.0%) patients who developed lung metastasis and control group without lung metastasis. The high-risk variables associated with lung metastasis were reviewed by univariate analysis and multivariate analysis.</p><p><b>RESULTS</b>Lung metastasis developed in 16 patients, including 10 cases with unilateral lung metastasis and 6 with bilateral. The median duration from colorectal surgery to identification of lung metastasis was 13.9 months. The diagnosis rate of pulmonary metastasis by enhanced chest CT was 81.3%(13/16). Univariate analysis identified the following associated with significant factors associated with pulmonary metastasis: primary tumor location(P=0.003), adjuvant chemotherapy(P=0.034), TNM stage(P=0.005) and preoperative serum carcinoembryonic antigen(CEA) level (P=0.001). Multivariate analysis revealed that primary tumor location(rectum) and preoperative serum CEA level(≥5 μg/L) were independent risk factors for pulmonary metastasis(both P<0.05).</p><p><b>CONCLUSIONS</b>Primary tumor location and elevated preoperative CEA level are independent risk factors for pulmonary metastasis. Strict postoperative follow-up and routine chest enhanced CT examination is necessary for this particular patient population.</p>

Regulation mechanism study of S100A6 on invasion and metastasis in gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To detect the expression of S100A6 in gastric cancer, and to investigate the regulation mechanism of S100A6 in invasion and metastasis of gastric cancer.</p><p><b>METHODS</b>Expression of S100A6 protein in gastric cancer specimens, tissue adjacent to cancer, liver and lymph node metastasis tissue specimens was detected by immunohistochemical staining in 166 patients with gastric cancer from January 1995 to December 2001. Their association with clinicopathological factors was analyzed. Chromatin Immunoprecipitation-chip was used to detect the downstream factors potentially regulated by S100A6 in gastric cancer cell lines KATO3. S100A6 gene was transfected into gastric cancer cell line AGS, and cell invasion experiment and real time Q-polymerase chain reaction(RT Q-PCR) were used to detect the cell invasive ability and the mRNA expression of invasion-related factors (CDK5 and FLJ12438) in transfection group, negative control group and blank control group, respectively.</p><p><b>RESULTS</b>Low expression of S100A6 protein was found in cytoplasm of peritumoral tissues. In gastric cancer, liver and lymph node metastasis tissues, S100A6 protein expression was up-regulated in cytoplasm and (or) nuclei, especially in the tumor cells of invasive edge. The expression rates of gastric cancer, liver and lymph node metastasis tissues were 67.5%(112/166), 92.9%(26/28) and 100% (30/30) respectively. The high expression of S100A6 was associated with tumor local invasion, lymph node metastasis, cancer embolus, distant metastasis and TNM stages(all P<0.05). The transmembrane cell number was 31.3±5.5 in the S100A6 transfection group, significantly higher than that in negative control group (7.7±1.5) and blank control group (9.3±2.1)(both P<0.05), indicating an increase of cell invasion after S100A6 transfection. In transfection group, CDK5 mRNA expression was significantly higher than that in negative control group and blank control group(P<0.05). While FLJ1243 mRNA expression was similar among the three groups(P<0.05).</p><p><b>CONCLUSION</b>S100A6 may affect the malignant biological behavior of gastric cancer cells by regulating the expressions of down-stream invasion-associated factors, such as CDK5.</p>

Application of biotherapy in recurrent or metastatic gastric cancer / 中华胃肠外科杂志

Post-operative recurrence and metastasis remain the leading causes of death for patients with gastric cancer. The major determinants of recurrence and metastasis are the biological characteristics of cancer cells and the immunological status of the patients. In recent years, due to the target-specificity, biotherapy has yielded efficacious responses in diverse clinical applications for cancer treatment, partially for the treatment of recurrence and metastasis of gastric cancer. However, because of the high diversities in clinical manifestations, patients' condition, and tumor's characteristics, there is no ideal strategy of biotherapy established for the prevention and treatment of recurrence and metastasis in gastric cancer. Therefore, a lot of work need to be done in basic research and clinical trial to make the biotherapy effective in treatment of gastric cancer recurrence.

Analysis of splenic hilar lymph node metastasis in advanced gastric cancer and dissection techniques / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the status of splenic hilar lymph nodes(No.4sa, No.10 or No.11d lymph nodes) metastasis and to investigate the proper dissection technique in patients with advanced gastric cancer.</p><p><b>METHODS</b>A retrospective study was performed to investigate 590 patients who underwent D2 curative proximal or total gastrectomy for gastric carcinoma from January 2006 to December 2009. Clinicopathological factors such as sex, age, location of the primary tumor, tumor sizes, gross type, depth of invasion, microscopic classification, neoadjuvant chemotherapy and the metastasis of adjacent lymph node were analyzed with univariate and multivariate analysis. Influence of combined splenectomy or pancreatectomy on lymph node dissection was also investigated.</p><p><b>RESULTS</b>The overall ratio of metastatic lymph node(positive lymph nodes/lymph nodes harvested) in the splenic hilum was 17.5%(99/565). The positive rates of No.4sa, No.10, No.11d lymph nodes were 17.8% (41/230), 13.9%(29/209), and 22.8%(29/127), respectively. A total of 7.1%(42/590) of the patients had lymph node metastasis in the splenic hilum. Multivariable logistic regression analysis showed that age, tumor size, depth of tumor invasion, positive metastasis of No.4sb lymph node were independent risk factors for lymph node metastasis in the splenic hilum region. When comparing patients undergoing combined splenectomy or pancreatectomy(n=23) and those who did not undergo combined organ resection (n=553), the ratios of metastatic lymph node in the splenic hilum were 14.8%(4/27) and 17.2%(91/527), respectively, and the difference was not statistically significant(P>0.05). The postoperative complication rates were 26.1%(6/23) and 5.4%(30/553), respectively, and the difference was statistically significant(P<0.05). The operative mortality rates were 4.3% and 0.9%, respectively, and the difference was not statistically significant(P>0.05).</p><p><b>CONCLUSIONS</b>Metastasis to lymph nodes in the splenic hilum region in patients with gastric cancer possesses a certain pattern, and it is associated with tumor location, size, depth of invasion, and metastasis in No.4sb. Combined resection of the spleen or pancreas does not result in increased number of harvested lymph nodes or positive lymph nodes, yet is associated with higher complication rate. Therefore, combined organ resection should be meticulous.</p>

Clinicopathological observation of gastric cancer with pathological complete response following neoadjuvant chemotherapy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To observe the clinicopathological characteristics of gastric cancer with pathological complete response(pCR) following neoadjuvant chemotherapy.</p><p><b>METHODS</b>Data of gastric cancer patients who received neoadjuvant chemotherapy from 2002 to 2008 in the Beijing Cancer Hospital were reviewed. Five cases were found to have pCR. The slides were reviewed by two experienced pathologists independently. Histological structure, morphology of tumor cells, morphology and quantity of stromal cells were evaluated.</p><p><b>RESULTS</b>Structure of the gastric wall was distinguishable in all the 5 cases, while distortion and rupture of muscular layer were found in 2 cases. Exudative inflammatory reaction was present in the whole gastric wall including the serosa layer. Three patients had ulcerative lesions with epithelial layer shedding, and atypical hyperplasia was found around the border of the ulcer, and vascular endothelial cells were swollen. Residual distorted necrotic tumor cells resided in 1 case only and no residual tumor cells was present in the other 4 patients. Significant hyperplasia of fibroblasts was present in 4 cases, large amount of lymphocytes infiltration in 3 cases including concurrent plasma cell infiltration in 1 case, multinucleated giant cell reaction in the muscular layer of 1 case, and foam cells aggregation in 1 case with mucinous adenocarcinoma. In addition, there were 2 cases with pCR had lymph node metastasis.</p><p><b>CONCLUSIONS</b>For cases with pCR following neoadjuvant chemotherapy, heterogeneity of stromal cells reaction is found in previous tumor site. Furthermore, the response of primary tumor does not necessarily parallel to that of lymph nodes.</p>

Gastric neuroendocrine carcinoma and gastric carcinoma with neuroendocrine cell differentiation: a clinical and prognostic analysis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features, treatment, and prognosis of gastric neuroendocrine carcinoma and gastric carcinoma with neuroendocrine cell differentiation.</p><p><b>METHODS</b>A total of 19 patients were treated for gastric neuroendocrine cancer or gastric cancer with neuroendocrine differentiation in the Beijing Cancer Hospital from January 1997 to December 2008. Clinical data were retrospectively analyzed.</p><p><b>RESULTS</b>Fourteen patients had neuroendocrine carcinoma in the gastric cardia (n=9) or gastric body(n=5), and 5 patients had gastric cancer with neuroendocrine differentiation in the gastric cardia(n=2), the antrum(n=2), and the entire stomach(n=1). According to the International Classification of Disease for Oncology(2000), patients were divided into gastric carcinoid type I((n=2, 10.5%), type III( sporadic gastric carcinoid (n=9, 47.4%), small cell carcinoma of the stomach(n=3,15.8%), and gastric cancer with neuroendocrine cell differentiation(n=5, 26.3%). Clinical manifestations were mostly non-specific. Diagnosis was based on pathological and immunohistochemical examination. Eighteen patients underwent surgery including radical subtotal gastrectomy and total gastrectomy, of whom 3 underwent simultaneous resection of the liver metastasis. The remaining one patient with small cell carcinoma of the gastric body received chemotherapy alone because of unresectable liver metastasis. The survival rate was 73.7% at 1 year and 38.6% at 3 years.</p><p><b>CONCLUSIONS</b>Gastric neuroendocrine carcinoma usually develops in the cardia and body of the stomach. Gastric carcinoma with neuroendocrine cell differentiation can occur in any locations of the stomach. Immunohistochemistry is important to the diagnosis. Radical resection is the main treatment.</p>