Spinal cord injury (SCI) is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes, such as excessive reactive oxygen species (ROS) ...produced by the infiltrated inflammatory immune cells and released to the extracellular microenvironment, leading to the widespread apoptosis of the neuron cells, glial and oligodendroctyes. In this study, a thioketal-containing and ROS-scavenging hydrogel was prepared for encapsulation of the bone marrow derived mesenchymal stem cells (BMSCs), which promoted the neurogenesis and axon regeneration by scavenging the overproduced ROS and re-building a regenerative microenvironment. The hydrogel could effectively encapsulate BMSCs, and played a remarkable neuroprotective role in vivo by reducing the production of endogenous ROS, attenuating ROS-mediated oxidative damage and downregulating the inflammatory cytokines such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), resulting in a reduced cell apoptosis in the spinal cord tissue. The BMSCs-encapsulated ROS-scavenging hydrogel also reduced the scar formation, and improved the neurogenesis of the spinal cord tissue, and thus distinctly enhanced the motor functional recovery of SCI rats. Our work provides a combinational strategy against ROS-mediated oxidative stress, with potential applications not only in SCI, but also in other central nervous system diseases with similar pathological conditions.
A ROS-scavenging hydrogel is loaded with bone marrow-derived mesenchymal stem cells (BMSCs), which scavenges the overproduced ROS and re-builds a regenerative microenvironment, and thereby promotes axon regeneration post spinal cord injury in vivo. Display omitted
•A ROS-scavenging hydrogel protects the encapsulated BMSCs in an inflammatory environment and attenuates inflammation.•A ROS-scavenging hydrogel significantly reduces oxidative damage and inflammation in spinal cord injury.•A BMSCs-encapsulated ROS-scavenging hydrogel promotes axon regeneration in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Microvascular invasion (MVI) is a risk factor for tumor recurrence after hepatectomy in hepatocellular carcinoma (HCC) patients.
Objective
This study aimed to investigate the efficacy and ...safety of postoperative adjuvant transarterial infusion chemotherapy (TAI) with the FOLFOX regimen for HCC patients with MVI.
Methods
In this prospective, phase III, randomized, open-label, controlled clinical trial, HCC patients with histologically confirmed MVI were randomly assigned (1:1) after hepatectomy to receive either one to two cycles of adjuvant TAI (AT group) or follow-up without any adjuvant treatment (FU group). The primary endpoint was disease-free survival (DFS), while secondary endpoints were overall survival (OS) and safety.
Results
Between June 2016 and April 2019, 127 patients were randomly assigned to the AT group (
n
= 63) or FU group (
n
= 64). Clinicopathological characteristics of the two groups were well-balanced. The 6-, 12-, and 18-month OS rates for the AT group were 100.0%, 97.7%, and 97.7%, respectively, and 94.5%, 89.6%, and 78.5% for the FU group, respectively. The 6-, 12-, and 18-month DFS rates for the AT and FU groups were 84.7%, 61.8%, and 58.7%, and 62.9%, 48.1%, and 38.6%, respectively. OS and DFS were significantly better in the AT group than in the FU group (
p
= 0.037 and 0.023, respectively). No patients in the AT group experienced grade 3 or more severe adverse events.
Conclusions
Adjuvant TAI after hepatectomy may bring survival benefits to HCC patients with MVI.
Trial registration
Trial number: NCT03192618.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
There is a lack of effective treatment to improve the prognosis of intrahepatic cholangiocarcinoma (ICC). Programmed cell death protein-1 (PD-1)-targeted immunotherapy has shown promising results in ...a variety of malignant tumours. However, in patients with advanced ICC, the safety and efficacy of anti-PD-1 agents remain unclear.
Forty-two advanced ICC patients treated with anti-PD-1 agents from August 2018 to December 2020 were retrospectively analyzed. Tumour response, overall survival (OS), progression-free survival (PFS), and time to tumour progression (TTP) were evaluated. Adverse events were also recorded.
The median duration of follow-up was 12.1 months, and the median time of treatment was 6.7 months for all patients. The median OS, median PFS, and median TTP for the whole cohort were 19.3 months, 11.6 months, and 11.6 months, respectively. The overall response rate (ORR) and disease control rate (DCR) for the whole cohort were 23.8% and 85.7%, respectively. Of the 42 evaluable individuals, two (4.8%) had hyperprogressive disease. The most common adverse events (AEs) were pain (n = 6; 14.3%), anorexia (n = 4; 9.5%), hypertension (n = 4; 9.5%), pyrexia (n = 3; 7.1%), cough (n = 3; 7.1%), and hypothyroidism (n = 3; 7.1%). The median OS of patients with albumin-bilirubin (ALBI) grade 1 was longer than that of patients with ALBI grade 2 (19.3 months vs. 14.7 months). The median PFS did not show a significant difference between ALBI grade 1 and grade 2 patients (13.6 months vs. 6.9 months).
PD-1-targeted immunotherapy showed promising efficacy and safety in advanced ICC patients.
Key messages
PD-1-targeted immunotherapy is a safe and effective treatment for advanced ICC patients.
This study provides therapeutic strategy for advanced ICC patients.
The optimal treatment of stage IV rectal cancer remains controversial. The purpose of this study was to assess the treatment outcomes and toxicity of neoadjuvant chemotherapy and radiotherapy ...followed by local treatment of all tumor sites and subsequent adjuvant chemotherapy in stage IV rectal cancer patients with potentially resectable metastases.
Adult patients diagnosed with locally advanced rectal adenocarcinoma with potentially resectable metastases, who received neoadjuvant chemotherapy and radiotherapy from July 2013 and September 2019 at Sun Yat-sen University cancer center, were included. Completion of the whole treatment schedule, pathological response, treatment-related toxicity and survival were evaluated.
A total of 228 patients were analyzed with a median follow-up of 33 (range 3.3 to 93.4) months. Eventually, 112 (49.1%) patients finished the whole treatment schedule, of which complete response of all tumor sites and pathological downstaging of the rectal tumor were observed in three (2.7%) and 90 (80.4%) patients. The three-year overall survival (OS) and progression-free survival (PFS) of all patients were 56.6% (50.2 to 63.9%) and 38.6% (95% CI 32.5 to 45.8%), respectively. For patients who finished the treatment schedule, 3-year OS (74.4% vs 39.2%, P < 0.001) and 3-year PFS (45.5% vs 30.5%, P = 0.004) were significantly improved compared those who did not finish the treatment. Grade 3-4 chem-radiotherapy treatment toxicities were observed in 51 (22.4%) of all patients and surgical complications occurred in 22 (9.6%) of 142 patients who underwent surgery, respectively.
Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation and subsequent adjuvant chemotherapy offered chances of long-term survival with tolerable toxicities for selected patients with potentially resectable stage IV rectal cancer, and could be considered as an option in clinical practice.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Immune checkpoint blockade has led to a significant improvement of patient survival in metastatic colorectal cancer (CRC) with DNA mismatch repair-deficiency (dMMR)/microsatellite instability-high ...(MSI-H). However, not all these patients are sensitive to monoimmunotherapy. We firstly presented a case series of advanced dMMR/MSI-H CRCs treating with PD-1 inhibitor-based chemoradioimmunotherapy (CRIT).
We assessed the short-term efficacy and safety of CRIT in advanced dMMR/MSI-H CRCs, and also did next-generation sequencing (NGS) assays.
Our analysis included five advanced dMMR/MSI-H CRCs who have received toripalimab-based CRIT. Toripalimab was given 240mg every three weeks, and the radiation dose was 45-50 gray in 25 fractions. Chemotherapy regimens consisted of CAPOX in three patients, capecitabine in one patient, and mFOLFOX6 in one patient. Initially, two patients displayed complete response (CR), and three patients achieved partial response (PR) on imaging findings. Afterwards, one PR patient was confirmed pathological complete response after surgery, leading to three CR cases in total. Hematological toxicity was the most common adverse effect, and only two patients developed mild immune-related adverse effects besides. All the treatment-related adverse events were under control. Based on the NGS results, the median intratumor heterogeneity was 0.19 (range 0-0.957), which was less in CR patients than PR patients (
= 0.019). Genetic mutations at DNA damage repair genes and the
gene were also observed.
For advanced dMMR/MSI-H CRC, anti-PD-1 based CRIT is effective and safe. Further studies are required to better clarify the potential role and mechanism of CRIT as a viable therapeutic strategy in this population.
Portal/hepatic vein tumor thrombosis (PVTT/HVTT) in hepatocellular carcinoma (HCC) is a sign of advanced stage disease and is associated with poor prognosis. This study investigated the surgical ...outcomes of patients with HCC and PVTT/HVTT to determine the most appropriate surgical treatment strategy for these patients.
The study population included 77 HCC patients from January 2004 to June 2009 who underwent hepatectomy in our department and were diagnosed with PVTT/HVTT based on pathological examination. The patients were divided into two groups: in group 1, PVTT/HVTT was located in the hepatic resection area and removed with the tumor en bloc (38 cases); in group 2, PVTT/HVTT was beyond the resection line and removed by suction or thrombectomy (39 cases). Concerning the factor of surgical margins, the patients were further divided into four subgroups: group 1A: patients in group 1 with surgical margins ≤1 cm (28 cases); group 1B: patients in group 1 with surgical margins >1 cm (9 cases); group 2A: patients in group 2 with surgical margins ≤1 cm (28 cases); and group 2B: patients in group 2 with surgical margins >1 cm (9 cases).
Most of the characteristics of groups 1 and 2 were similar. Patients in group 2 had significantly higher median blood loss (p=0.002) and higher blood transfusion rate (p=0.002) during the operation, which were not considered prognostic factors (p=0.323 and 0.571, respectively). The median overall survival (OS) duration in group 1 was significantly longer than that in group 2 (14.3 vs. 10.4 months, p=0.047). The median OS durations in groups 1A, 1B, 2A, and 2B were 14.3, 42.7, 7.5, and 18.0 months, respectively, which were significantly different(p=0.018).
When PVTT/HVTT is located in the hepatic resection area and removed with the tumor en bloc, the median OS duration is longer. Based on this finding, widening the surgical margins when technically possible may increase OS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Colorectal cancer (CRC) rarely occurs in children and adolescents. This study aimed to perform a retrospective analysis and disclose more detailed information about CRC in patients under ...20 years old.
Methods
Medical records of CRCs in patients under 20 years old referred to three tertiary hospitals in China from September 2000 to July 2019 were retrospectively reviewed. Clinicopathological characteristics, treatment processes and laboratory findings were summarized and treatment outcomes and prognostic factors were analyzed.
Results
A total of 33,394 CRC medical records were analyzed, and we identified seventy (0.21%) CRCs in patients under 20. The most common primary tumor location was the left hemicolon (35.7%). The prominent pathological types were mucinous adenocarcinoma (22.9%) and signet ring cell carcinoma (22.9%). Nearly half (47.1%) of the patients presented with distant metastasis at diagnosis. The fractions of patients with deficient mismatch repair (dMMR) protein expression and microsatellite instability-high (MSI-H) were 23.8% (5/21) and 71.4% (5/7), respectively. Forty-four patients underwent radical surgery. Fifty-five patients received chemotherapy and six patients received radiotherapy. One dMMR/MSI-H rectal cancer patient received immunotherapy and achieved a clinically complete response. The median overall survival (OS) time was 80 months. The 3-year and 5-year OS rates were 61.8% and 57.2%, respectively. An absence of distant metastasis was a favorable factor for OS. For stage II/III CRCs, classic adenocarcinoma and radical surgery were favorable factors for OS. For stage IV CRCs, primary location at the colon was a favorable factor for OS.
Conclusion
Child and adolescent CRC patients are likely to have distant metastasis, undifferentiated, left hemicolon location, and a dMMR/MSI-H phenotype at diagnosis. Additional efforts are needed to improve their survival outcomes.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Colorectal cancer, radiotherapy and gut microbiota Zhang, Shu; Wang, Qiaoxuan; Zhou, Chengjing ...
Chinese Journal of Cancer Research/Chinese journal of cancer research,
02/2019, Volume:
31, Issue:
1
Journal Article
Peer reviewed
Open access
Colorectal cancer is closely related to inflammation and immune response. Radiotherapy, as a major treatment for colorectal cancer, plays a central role in cancer control. Inflammation caused by ...ionizing radiation can exert either anti- or pro-tumorigenic effects. Additionally, radiotherapy can elicit an anti-tumor response not only in radiation of target lesions but also in radiation of remote lesions. However, the immune mechanism underlying this effect has not been thoroughly elucidated yet. The combination therapeutic regimen of radiotherapy with other therapeutic methods, including chemotherapy and immunotherapy, has been applied in clinical practice. Meanwhile, radiation toxicity and radiosensitivity have long been problems that affect a patient's quality of life and morbidity. Researchers have found that the abovementioned problems are closely associated with gut microbiota. Here we discuss the impact of immune response induced by radiotherapy on tumor regression and the impact of intestinal flora on the consequent clinical efficacy.
Purpose
For hepatocellular carcinoma (HCC) located in the left lateral lobe, the optimal surgical procedure is still controversial. This study aimed to optimize surgical strategies and to construct a ...nomogram to predict the postoperative survival of patients with HCC.
Methods
Between 1 January 2005 and 30 September 2018, a total of 493 patients were enrolled. Propensity score matching (PSM) was performed between the left lateral lobectomy (LLL) and left hepatectomy (LH) groups (1:1). The study endpoints were overall survival (OS), recurrence‐free survival (RFS), and safety. A nomogram was generated using a multivariate Cox proportional hazards model. The discriminative ability and calibration of the nomogram were evaluated using C‐statistics and calibration plots.
Results
After matching, 87 pairs were included. The LH group had better 1‐, 3‐, and 5‐year OS rates than the LLL group (88%, 73%, and 69% vs. 73%, 57%, and 49%, respectively; p = 0.017). The 1‐, 3‐, and 5‐year RFS rates of the LH group were similar to those of the LLL group (64%, 49%, and 46% vs. 63%, 51%, and 42%, respectively; p = 0.652). There were no significant differences in postoperative complications. Eight factors were integrated into the nomogram and it had good discriminative ability and calibration.
Conclusion
Our data revealed that compared to LLL, LH may result in better OS and have similar postoperative complications for HCC. The nomogram may serve as a practical tool for the individual prognostic evaluation of patients with HCC.
Left hepatectomy is a more feasible and safer surgical approach for the treatment of HCC in the left lateral lobe. The proposed nomograms can provide patient‐specific survival information for patients with HCC in the left lateral lobe after surgery.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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