[Molecular mechanism and treatment strategy of colorectal cancer peritoneal metastasis].

Peritoneal metastatic colorectal cancer (pmCRC) is common and has been considered as the terminal stage. The theory of "seed and soil" and "oligometastasis" are the acknowledged hypotheses of pathogenesis of pmCRC. In recent years, the molecular mechanism related to pmCRC has been deeply researched. We realize that the formation of peritoneal metastasis, from detachment of cells from primary tumor to mesothelial adhesion and invasion, depends on the interplay of multiple molecules. Various components of tumor microenvironment also work as regulators in this process. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been widely used in clinical practice as an established treatment for pmCRC. Besides systemic chemotherapy, targeted and immunotherapeutic drugs are also increasingly used to improve prognosis. This article reviews the molecular mechanisms and treatment strategies related to pmCRC.

[Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH)].

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

[Association between obesity and risk for colorectal advanced adenoma].

Objectives: To understand the association between obesity and the risk for colorectal advanced adenoma. Methods: Community residents aged 45 to 74 who had participated in the Shanghai community-based colorectal cancer (CRC) screening project in 2008 were included in our study. Anthropometries information including body weight, height and risk factors for colorectal advanced adenoma were collected. Results on colonoscopic diagnosis and personal health records were used for supplementary outcome information retrieval. Multivariate Cox proportional hazard regression models were used to evaluate the hazard ratio (HR) and 95%CI of obesity on the risk for colorectal advanced adenoma. Results: 20 811 residents were followed up for 122 739.36 person-years, with a median follow-up time of 5.87 years. A total of 657 cases of advanced adenomas were identified. After adjusting for potential confounding risk factors such as age, sex, family history of CRC, level of education, marriage, cigarette smoking, alcohol drinking, foods intake including fat, fried or pickled, vegetables and fruits etc., the HR was 1.25 (95%CI: 1.04-1.51) for obese people when compared with the normal weight persons. Further stratified analysis by age, gender and family history of CRC, results showed that obese people had a much higher risk of colorectal advanced adenoma than those with normal weight (male: HR=1.57, 95%CI: 1.20-2.04; more than 60- year-old: HR=1.63, 95%CI: 1.23-2.16). Conclusion: Data from this large scale population-based study revealed that obesity might be an independent risk factor for colorectal advanced adenoma and the risk increases along with the increase of BMI in China.

[Clinical characteristics and prognosis of 35 patients with therapy-related hematological neoplasms].

OBJECTIVE: To investigate the morbidity, treatment outcomes and prognosis of 35 therapy-related hematological neoplasms patients. METHODS: A total of 35 cases of therapy-related hematological neoplasms were examined genetically and immunologically using flow cytometry, karyotype analysis and FISH, and their clinical data were retrospective analyzed and literatures were reviewed. RESULTS: Among 35 patients, there were 20 cases of therapy-related acute myeloid leukemia (t-AML), 4 cases of therapy-related acute lymphoblastic leukemia (t-ALL), 1 case of acute mixed leukemia, therapy-related non-hodgkin' s lymphoma (t-NHL) in 8 cases and myelodysplastic syndrome (t-MDS) in 2 cases. The median onset of t-HN was 29(16-90) months, the median OS of t-HN was 14(1-60) months, and 3 years of OS was 17.1%. Among therapy-related acute leukemia (t-AL) patients, 40% (10/25) patients had combined complex karyotype, 36% (9/25) patients with MLL gene rearrangement, 12% (3/25) patients with combined AML/ETO fusion gene, 1 case with NPM1 point mutation and 1 case with P16 gene deletion. CONCLUSIONS: Therapy-related hematological neoplasms had a worse prognosis.

Clinicopathological features and prognostic factors of rectal gastrointestinal stromal tumors.

AIM: Rectal gastrointestinal stromal tumor (GIST) was a rare disease. This study sought to summarize clinicopathological features and prognostic factors of rectal GISTs. METHODS: Clinicopathological characteristics and prognostic factors of rectal GISTs were investigated by reviewing patients undergoing curative resection at the Fudan University Shanghai Cancer Center between 1986 and 2010. RESULTS: Twenty-one patients, 15 male and 6 female, were included. The mean age of onset was 51 years. The most common initial presentation was hematochezia (7 cases). Eleven patients underwent radical resection, and the other 10 received local resection. No lymph node metastases were identified. All cases were positive for CD117. Seventeen patients were classified as high National Institutes of Health (NIH) risk category. The 5-year disease-free survival (DFS) and overall survival were 33 and 46 %, respectively. Fifteen cases had recurrence postoperatively. Both univariate and multivariate analyses demonstrated the NIH risk category (p = 0.028) and hematochezia symptom (p = 0.014) were independent prognostic factors of the DFS of patients. CONCLUSIONS: Hematochezia was the most common initial symptom. Over 50 % of patients received radical surgery. More than 80 % of patients were at high NIH risk of recurrence. Hematochezia symptom and high NIH risk category indicated poor prognosis of rectal GISTs.

Interaction between synchronous bilateral prophylactic oophorectomy and adjuvant chemotherapy in female patients with locally advanced colorectal cancer.

AIM: In this study we explored the prognostic impact of synchronous bilateral prophylactic oophorectomy in female patients with primary colorectal cancer undergoing radical surgery. METHOD: From 1991 to 2000, 267 female patients with stage II or stage III colorectal cancer, who had undergone curative resection, were retrospectively reviewed. In 224 patients, the ovaries were preserved. The other 43 patients underwent synchronous bilateral prophylactic oophorectomy. Univariate and multivariate analyses (Kaplan-Meier and Cox regression, respectively) were used to evaluate the effect of prophylactic oophorectomy and other clinical factors on the prognosis of patients. RESULTS: Both univariate and multivariate analyses showed that tumor stage and adjuvant chemotherapy were the only two significant clinical factors that affected the 5-year overall survival of patients (P < 0.01). There was no significant difference in the 5-year overall survival between patients who had, or had not, undergone prophylactic oophorectomy (75%vs 73%, P > 0.05). In the subgroup analysis by adjuvant chemotherapy, the 5-year overall survival in patients receiving adjuvant chemotherapy was similar between nonoophorectomy and oophorectomy groups. However, in patients without adjuvant chemotherapy, the oophorectomy group was shown to have a significantly better 5-year overall survival than the nonoophorectomy group (76%vs 51%, P = 0.047). CONCLUSION: Prophylactic oophorectomy may improve the overall survival of female patients with locally advanced colorectal cancer without adjuvant chemotherapy, but its survival benefit vanished in patients receiving adjuvant chemotherapy. The role of prophylactic oophorectomy may be substituted by adjuvant chemotherapy, which makes prophylactic oophorectomy unnecessary during surgery for locally advanced colorectal cancer.

Educational intervention for preventing bloodborne infection among medical students in China.

Although medical students are known to be at risk for bloodborne infections, there have been no systematic studies, effective intervention programmes, or guidelines for them in China. We developed prevention guidelines, implemented an intervention, and evaluated the effectiveness of knowledge among medical students. This study was designed as a cluster randomised controlled trial. All those who completed a consent form were randomly assigned either to an intervention or to a control group. The intervention group underwent an educational intervention programme consisting of a series of lectures and videos following a baseline survey. The control group completed the same intervention programme after the study was completed. A questionnaire of 25 items was sent to participants three months and nine months after the initial intervention programme. Outcomes measured before and after intervention included knowledge of transmission route, first-aid care, and post-exposure prophylaxis. Pearson's chi(2)-test was used, and the efficacy of students was analysed to control for bias. Intervention in the form of a one-time bloodborne pathogen educational prevention programme for Chinese medical students had little effect on knowledge.

Controlling the growth of ZnO quantum dots embedded in silica by Zn/F sequential ion implantation and subsequent annealing.

We report the formation of embedded ZnO quantum dots (QDs) by Zn and F ion sequential implantation and subsequent annealing. Optical absorption and photoluminescence spectrum measurements, transmission electron microscopy bright field images and selected area electron diffraction patterns indicate that ZnO QDs were formed after annealing in air or vacuum at temperatures higher than 500 °C. Atomic force microscopy images show a comparatively flat surface of the annealed samples, which indicates that only very few Zn atoms are evaporated to the surfaces. The formation of ZnO QDs during the thermal annealing can be attributed to the direct oxidization of Zn nanoparticles by the oxygen molecules in the substrate produced during the implantation of F ions. The quality of ZnO QDs increases with the increase of annealing temperature.

ZnO single-crystal films fabricated by the oxidation of zinc-implanted sapphire.

Zinc oxide single-crystal films are prepared by the oxidation of zinc-implanted sapphire at 700 °C for 2 h in oxygen ambient. The cross-section transmission electron microscopy image and the selected-area electron diffraction (SAED) pattern show that ZnO single-crystal films are formed on the surface of the zinc-implanted sapphire substrate. The quality and excitonic properties of the single-crystal ZnO films are studied through absorption spectra, the photoluminescence spectra and resonant Raman spectrum. The mechanisms for the formation of single-crystal ZnO films are discussed.