[The effect of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy on peritoneal carcinomatosis from colorectal cancer].

Objective: To evaluate the safety and efficacy of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+ HIPEC) in patients with peritoneal carcinomatosis from colorectal carcinoma (CRC PC). Methods: The clinical and follow-up data of 90 consecutive CRC PC patients underwent CRS+ HIPEC in Beijing Shijitan Hospital from January 2015 to June 2018 were collected. Kaplan-Meier method and parallel Log rank test were used for survival analysis. Cox regression model was used for univariate and multivariate analysis. Results: A total of 90 CRC PC patients underwent CRS+ HIPEC, the median age was 53 years (rage: 13 to 81 years), and 51 cases were male, while other 39 were female. The median overall survival (mOS) was 21.9 months (95%CI: 15.7, 28.1). The 1-, 2-, 3-, and 5-year survival rates were 77.8%, 48.6%, 21.1%, and 5.5%, respectively. The incidence rate of serious adverse event (SAE) was 8.9% (8/90). The mortality rate of perioperative period was 2.2% (2/90). Univariate analysis showed the age (P=0.040), primary tumor site (P=0.020), preoperative carbohydrate antigen 125 (CA125) level (P<0.001), peritoneal cancer index (PCI) (P<0.001), completeness of cytoreduction (CC) (P<0.001), ascites (P=0.012) and postoperative adjuvant chemotherapy (P<0.001) were significantly associated with the OS. Multivariate Cox-analysis identified preoperative CA125 level(P=0.033), CC of 0 to 1 (P=0.014), and adjuvant chemotherapy postoperative (P=0.002) were independent prognostic factor for OS. Conclusions: CRS+ HIPEC can improve survival for CRC PC patients with acceptable morbidity and mortality. Stringent patient selection and complete CRS are two key factors for better survival.

[Effects of neuromuscular exercise therapy on the joint stability of patients with knee osteoarthritis].

Objective: To evaluate the effects of neuromuscular exercise therapy on joint stability of knee osteoarthritis (OA) patients. Methods: One hundred and ten patients with knee OA were enrolled in this ongoing prospective cohort study at Arthritis Clinic and Research Center, Peking University People's Hospital from September 2017 to October 2018. The treatment consisted of six-week neuromuscular exercise therapy. The participants were followed up at 6 weeks and 3 months after the therapy. The stability of the joint was evaluated by the index of knee joint stability (IKJS), which was extracted by a novel knee-aiming task combined with the multiscale entropy (MSE) analysis of the complexity of the light spot trajectories. The secondary outcomes were pain on the visual analogue scale (VAS, 0-100), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), quality of life on the Euro-quality of life-5 Dimensional (EQ-5D) VAS form, 30-second chair stand test and 40-meter walk test. One-way repeated measures ANOVA analysis was applied to compare the outcomes at baseline and 6 weeks and 3 months. Pearson partial analysis was used to investigate the correlation between the IKJS and the Kellgren-Lawrence (K/L) rate, pain and knee function. Results: Ninety-six participants ((65±8) years, 21 males, 75 females) completed 3-month follow-up. There was a significant improvement in IKJS at the 6-week visit compared with that at baseline (0.369, 95% confidence interval (CI) 0.241-0.496, P<0.001). The IKJS dropped at 3-month visit compared with 6-week visit, but was still better than that at baseline (0.178, 95%CI: 0.042-0.314, P=0.008). The correlation between IKJS and K/L rate, severity of pain, WOMAC or knee function was not significant (r=-0.131, -0.059, -0.231, 0.124, all P>0.05). There was improvement in pain VAS, WOMAC, EQ-5D-VAS, 30-second chair stand test and 40-meter walk test at 6 weeks and 3 months (all P<0.05). Conclusion: The neuromuscular exercise therapy is effective in improving the joint stability of the knee OA patients. However, the effect gradually diminished over time. In addition, neuromuscular exercise can help relieve pain, improve the function and quality of life in patients with knee OA.

[Effect of education and tailored exercise therapy on knee osteoarthritis patients].

Objective: To evaluate the effect of patient education and tailored exercise in the knee osteoarthritis (OA) patients. Methods: One hundred and eighty-five patients with knee OA were enrolled in this ongoing prospective cohort study at Arthritis Clinic and Research Center, Peking University People's Hospital since May, 2016.The treatment consisted of two one-hour sessions of patient education and six weeks of supervised, in-group, tailored exercise.The contents of the patient education were evidence-based and its overall focus was to increase the knowledge of the participants regarding OA and how to treat it.The exercise program was a neuromuscular exercise based on biomechanical and neuromuscular principles that aimed at restoring a neutral functional alignment of the lower extremities by improving sensorimotor control and obtaining compensatory functional stability.The outcomes were evaluated at baseline, 3 and 6 months, which included pain on the visual analogue scale (VAS, 0-100), quality of life on the Euro-quality of life-5 Dimensional (EQ-5D) VAS form, Knee Injury and Osteoarthritis Outcome Score (KOOS), 30-second chair stand test, 40-meter walk test and use of analgesics.The participants were also asked to rate their opinion of this program on a five-point scale (very satisfactory, satisfactory, neither satisfactory nor dissatisfactory, dissatisfactory, very dissatisfactory). One way analysis of variance was applied to compare the outcomes at baseline and 3 and 6 months follow-up. Results: One hundred and forty-two participants completed the 6-month follow-up.There were significant improvements in pain VAS, EQ-5D-VAS, 30-second chair stand test and 40-meter walk test at the follow-up at 3 and 6 months when compared with those at baseline (F=22.9, 8.4, 3.4, 4.1, 3.8, all P<0.05). The rate of analgesics use in the past two week at baseline was 43.2%, and it decreased to 18.9% at 6-month follow-up (P<0.001). Most participants (71.1%, 101 out of 142) rated the program as 'Very Satisfactory' and the rest (28.9%, 41 out of 142) rated the program as 'Satisfactory'. Conclusion: This program comprising the group patient education and tailored exercise therapy is effective in relieving pain, improving the function and quality of life in patients with knee OA.

[Analysis of the survival of 123 patients with intrahepatic cholangiocarcinoma after surgical resection].

OBJECTIVE: To investigate the prognostic factors for patients with intrahepatic cholangiocarcinoma after surgical resection. METHODS: The clinicopathological and follow-up data of 123 patients with intrahepatic cholangiocarcinoma who underwent surgical resection in Cancer Hospital, Chinese Academy of Medical Sciences between January 1999 and June 2015 were collected and reviewed, and their survival and prognosis were analyzed with the Kaplan-Meier method and Cox regression model. RESULTS: The median follow-up time was 22 months and median recurrence-free survival time was 8.97 months. The 1-, 2- and 3-year recurrence rates were 58.6%, 68.9% and 76.5%, respectively. Cox multivariate regression analysis showed that preoperative rise in CEA, lymph node metastasis, multiple lesions, extrahepatic invasion, and combination of tumor necrosis were significant adverse prognostic factors affecting the postoperative recurrence-free survival in patients with intrahepatic cholangiocarcinoma after surgical resection (P<0.05 for all). The median overall survival time was 21.17 months, and the 1-, 3- and 5-year overall survival rates were 76.6%, 33.2% and 26.1%, respectively. The Cox multivariate regression analysis showed that preoperative rise in CEA, lymph node metastasis, multiple lesions, and extrahepatic invasion were significant adverse prognostic factors affecting the postoperative overall survival in patients with intrahepatic cholangiocarcinoma after surgical resection(P<0.05 for all). CONCLUSION: Preoperative rise in CEA, lymph node metastasis, multiple lesions and extrahepatic invasion are significant adverse prognostic factors for patients with intrahepatic cholangiocarcinoma after surgical resection.

[Construction and evaluation of a nomogram for predicting the prognosis of patients with colorectal cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy].

Objectives: To construct a nomogram incorporating important prognostic factors for predicting the overall survival of patients with colorectal cancer with peritoneal metastases treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the aim being to accurately predict such patients' survival rates. Methods: This was a retrospective observational study. Relevant clinical and follow-up data of patients with colorectal cancer with peritoneal metastases treated by CRS + HIPEC in the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University from 2007 January to 2020 December were collected and subjected to Cox proportional regression analysis. All included patients had been diagnosed with peritoneal metastases from colorectal cancer and had no detectable distant metastases to other sites. Patients who had undergone emergency surgery because of obstruction or bleeding, or had other malignant diseases, or could not tolerate treatment because of severe comorbidities of the heart, lungs, liver or kidneys, or had been lost to follow-up, were excluded. Factors studied included: (1) basic clinicopathological characteristics; (2) details of CRS+HIPEC procedures; (3) overall survival rates; and (4) independent factors that influenced overall survival; the aim being to identify independent prognostic factors and use them to construct and validate a nomogram. The evaluation criteria used in this study were as follows. (1) Karnofsky Performance Scale (KPS) scores were used to quantitatively assess the quality of life of the study patients. The lower the score, the worse the patient's condition. (2) A peritoneal cancer index (PCI) was calculated by dividing the abdominal cavity into 13 regions, the highest score for each region being three points. The lower the score, the greater is the value of treatment. (3) Completeness of cytoreduction score (CC), where CC-0 and CC-1 denote complete eradication of tumor cells and CC-2 and CC-3 incomplete reduction of tumor cells. (4) To validate and evaluate the nomogram model, the internal validation cohort was bootstrapped 1000 times from the original data. The accuracy of prediction of the nomogram was evaluated with the consistency coefficient (C-index), and a C-index of 0.70-0.90 suggest that prediction by the model was accurate. Calibration curves were constructed to assess the conformity of predictions: the closer the predicted risk to the standard curve, the better the conformity. Results: The study cohort comprised 240 patients with peritoneal metastases from colorectal cancer who had undergone CRS+HIPEC. There were 104 women and 136 men of median age 52 years (10-79 years) and with a median preoperative KPS score of 90 points. There were 116 patients (48.3%) with PCI≤20 and 124 (51.7%) with PCI>20. Preoperative tumor markers were abnormal in 175 patients (72.9%) and normal in 38 (15.8%). HIPEC lasted 30 minutes in seven patients (2.9%), 60 minutes in 190 (79.2%), 90 minutes in 37 (15.4%), and 120 minutes in six (2.5%). There were 142 patients (59.2%) with CC scores 0-1 and 98 (40.8%) with CC scores 2-3. The incidence of Grade III to V adverse events was 21.7% (52/240). The median follow-up time is 15.3 (0.4-128.7) months. The median overall survival was 18.7 months, and the 1-, 3- and 5-year overall survival rates were 65.8%, 37.2% and 25.7%, respectively. Multivariate analysis showed that KPS score, preoperative tumor markers, CC score, and duration of HIPEC were independent prognostic factors. In the nomogram constructed with the above four variables, the predicted and actual values in the calibration curves for 1, 2 and 3-year survival rates were in good agreement, the C-index being 0.70 (95% CI: 0.65-0.75). Conclusions: Our nomogram, which was constructed with KPS score, preoperative tumor markers, CC score, and duration of HIPEC, accurately predicts the survival probability of patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

[Complete cytoreductive surgery is the key to improving survival of colorectal cancer patients with peritoneal metastases: comment on PROPHYLOCHIP and PRODIGE 7].

Peritoneal carcinomatosis (PC) is one of the difficult problems in the treatment of colorectal cancer (CRC). Based on several retrospective analyses of large samples and prospective randomized controlled studies (RCTs), NCCN and PSOGI recommend cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for selected CRC patients with mild to moderate PC. There are two important controversial issues in this field: the survival benefit of second-look surgery plus HIPEC for the patients with high risk of PC, and the specific benefit of HIPEC added to CRS for patients with PC. PROPHYLOCHIP found that second-look surgery plus HIPEC in patients at high risk of PC does not result in increased survival. PRODIGE 7 showed that overall survival (OS, 41.7 months vs. 41.2 months, P=0.99) and recurrence-free survival (RFS, 13.1 months vs. 11.1 months, P=0.43) were similar between the HIPEC group and non-HIPEC group, and suggested that HIPEC is not necessary for patients who underwent complete CRS. However, due to a series of problems in the design and implementation of this trial, the conclusion has caused great controversy and has not been widely recognized. Through detailed analysis and in-depth discussion, we believe that the benefit of HIPEC could not be denied according to PRODIGE 7. CRS + HIPEC is the embodiment and model of the concept of "Solid tumor treatment is surgery-based integrated treatment". CRS is the cornerstone of therapeutic strategies with curative intent for CRC PC and complete CRS is the key to improve the prognosis. Furthermore, HIPEC is an effective supplement to CRS.

[Efficacy of 1 384 cases of peritoneal carcinomatosis underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy].

Objective: Peritoneal carcinomatosis refers to a group of heterogeneous (primary or secondary) malignancies in the surface of the peritoneum. Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment strategy aiming at peritoneal carcinomatosis. This study analyzed the efficacy and safety of CRS+HIPEC in patients with peritoneal carcinomatosis, and explored prognostic factors. Methods: In this descriptive case-series study, the clinicopathological data of 1384 consecutive patients with peritoneal carcinomatosis treated in Zhongnan Hospital of Wuhan University (330 patients) and Shijitan Hospital of Capital Medical University (1054 patients) from January 2004 to January 2020 were collected retrospectively. Treatment patterns of CRS+HIPEC characteristics (operative time, number of resected organs, number of stripped peritoneum, number of anastomosis, and HIPEC regimens), safety [blood loss volume, postoperative severe adverse event (SAE) and treatment outcome], survival time and prognostic factors influencing survival were analyzed. The SAE was defined as grade III-IV adverse event according to the Peritoneal Surface Oncology Group International Textbook. Perioperative period was defined from the day of CRS+HIPEC to postoperative 30th day. OS was calculated from the day of CRS+HIPEC to the date of death or the last follow-up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison between groups. Cox regression model was used to identify the prognostic factors. Results: Among 1384 peritoneal carcinomatosis patients, 529 (38.2%) were male; median age was 55 (10-87) years old; median body mass index (BMI) was 22.6 kg/m(2); peritoneal carcinomatosis of 164 (11.8%) patients were from gastric cancer, 287 (20.7%) from colorectal cancer, 356 (25.7%) from pseudomyxoma peritonei, 90 (6.5%) from malignant peritoneal mesothelioma, 300 (21.7%) from gynecological cancer or primary peritoneal carcinoma, and 187 (13.5%) from retroperitoneal sarcoma, lung cancer, breast cancer, and other rare tumors. The median duration of CRS+HIPEC was 595 (90-1170) minutes, median number of resected organs was 2 (0-10), median number of resected peritoneal area were 4 (0-9), median peritoneal cancer index (PCI) was 21(1-39). Completeness of cytoreduction (CC) score of 0-1 was observed in 857 cases (61.9%). Regarding HIPEC regimens, there were 917 cases (66.3%) with cisplatin plus docetaxel, 183 cases (13.2%) with cisplatin plus mitomycin, 43 cases (3.1%) with adriamycin plus ifosfamide, and the other 240 cases (17.3%) with modified regimens. Perioperative SAE developed in 331 peritoneal carcinomatosis patients (23.9%) with 500 cases, of whom 21 patients (1.5%) died during the perioperative period due to ineffective treatment, while the others recovered after active treatment. During median follow-up time of 8.6 (0.3-82.7) months, there were 414 deaths (29.9%). The median OS was 38.2 months (95% CI: 30.6-45.8), and the 1-, 3-, 5-year survival rate was 73.5%, 50.4% and 39.3%, respectively. The median OS of peritoneal carcinomatosis patients from gastric cancer, colorectal cancer, pseudomyxoma peritonei, malignant peritoneal mesothelioma and female genital cancer or primary peritoneal carcinomatosis was 11.3 months (95% CI: 8.9-13.8), 18.1 months (95% CI: 13.5-22.6), 59.7 months (95% CI: 48.0-71.4), 19.5 months (95% CI: 6.0-33.0) and 51.7 months (95% CI: 14.6-88.8), respectively, and the difference among groups was statistically significant (P<0.001). Univariate and multivariate analyses revealed that the primary gastric cancer (HR=4.639, 95% CI: 1.692-12.724), primary colorectal cancer (HR=4.292, 95% CI: 1.957-9.420), primary malignant peritoneal mesothelioma (HR=2.741, 95% CI: 1.162-6.466), Karnofsky performance status (KPS) score of 60 (HR=4.606, 95% CI: 2.144-9.895), KPS score of 70 (HR=3.434, 95% CI: 1.977-5.965), CC score of 1 (HR=2.683, 95% CI: 1.440~4.999), CC score of 2-3 (HR=3.661,95% CI: 1.956-6.852) and perioperative SAE (HR=2.588, 95% CI: 1.846-3.629) were independent prognostic factors influencing survival with statistically significant differences (all P<0.05). Conclusions: CRS+HIPEC is an effective integrated treatment strategy for patients with peritoneal carcinomatosis, which can prolong survival with acceptable safety. Preoperative evaluation of patients' general condition is necessary and CRS+HIPEC should be carefully considered to perform for patients with preoperative KPS score <80. During the operation, the optimal CRS should be achieved on condition that safety is granted. In addition, it is necessary to prevent perioperative SAE to reduce the risk of death in peritoneal carcinomatosis patients.

Optimization and head-to-head comparison of MISSR-PCR, ERIC-PCR, RAPD and 16S rRNA evolutionary clock for the genotyping of Vibrio cholerae isolated in China.

PURPOSE: To establish a new genotyping method for Vibrio cholerae and compare it with other methods. MATERIALS AND METHODS: In the current study, a modified inter simple sequence repeat-polymerase chain reaction (MISSR-PCR) system was developed via several rounds of optimisation. Comparison study was then conducted between MISSR-PCR and three other methods, including enterobacterial repetitive intergenic consensus sequences-based PCR (ERIC-PCR), randomly amplified polymorphic DNA (RAPD) and 16S rRNA evolutionary clock, for the detection and genetic tracing of Vibrio cholerae isolated from seafood in China. RESULT: The results indicated that the MISSR-PCR system could generate the highest polymorphic fingerprinting map in a single round PCR and showed the best discriminatory ability for Vibrio cholerae genotyping by clearly separating toxigenic/nontoxigenic strains, local/foreign strains, and O1/O139/non-O1/non-O139 serogroup strains, comparing to ERIC-PCR, RAPD and 16S rRNA evolutionary clock. Moreover, the MISSR-PCR is superior to previously described traditional simple sequence repeat based PCR method on genotyping by more clearly separating different clusters. CONCLUSION: To the best of our knowledge, this is the first head-to-head comparison of four detection and genotyping methods for Vibrio cholerae The MISSR-PCR system established here could serve as a simple, quick, reliable and cost-effective tool for the genotyping and epidemiological study.

Coloanal anastomosis in radical surgery for low rectal carcinoma by intra-anal circular ligation.

Using self-made special supporting tube, coloanal anastomosis was performed by intra-anal ligation for radical surgery in 48 patients with low rectal carcinoma. The anastomoses were completed without suturing, and the results were quite satisfactory. Follow-up after operation revealed that the bowel movement and the sphincteric function were excellent in all patients. The anal canal and the anal sphincter were all kept intact and abdominal colostomy was not required for decompression. Anastomosis without suturing, least trauma, and short operation time made blood transfusion unnecessary during the operation. This technique is actually derived from Park's operation, and is considered a promising procedure for coloanal anastomosis in the radical surgery for low rectal carcinoma.