Colorectal cancer is considered one of the major malignancies that threaten the lives and health of people around the world. Patients with CRC are prone to post-operative local recurrence or metastasis, and some patients are advanced at the time of diagnosis and have no chance for complete surgical resection. These factors make chemotherapy an indispensable and important tool in treating CRC. However, the complex composition of the tumor microenvironment and the interaction of cellular and interstitial components constitute a tumor tissue with high cell density, dense extracellular matrix, and high osmotic pressure, inevitably preventing chemotherapeutic drugs from entering and acting on tumor cells. As a result, a novel drug carrier system with targeted nanoparticles has been applied to tumor therapy. It can change the physicochemical properties of drugs, facilitate the crossing of drug molecules through physiological and pathological tissue barriers, and increase the local concentration of nanomedicines at lesion sites. In addition to improving drug efficacy, targeted nanoparticles also reduce side effects, enabling safer and more effective disease diagnosis and treatment and improving bioavailability. In this review, we discuss the mechanisms by which infiltrating cells and other stromal components of the tumor microenvironment comprise barriers to chemotherapy in colorectal cancer. The research and application of targeted nanoparticles in CRC treatment are also classified.
BACKGROUND Colon cancer is a common malignant disease of the gastrointestinal tract and usually occurs at the junction of the rectum and sigmoid colon. Lymphatic and hematogenous metastases occur frequently in colon cancer and the most common metastatic sites include the liver, lung, peritoneum, bone, and lymph nodes. As a manifestation of advanced tumor spread and metastasis, soft tissue metastasis, especially skeletal muscle metastasis with bone metaplasia caused by colon cancer, is rare, accounting for less than 1% of metastases. CASE SUMMARY A 43-year-old male patient developed skeletal muscle metastasis with bone metaplasia of the right proximal thigh 5 mo after colon cancer was diagnosed. The patient was admitted to the hospital because of pain caused by a local mass on his right thigh. Positron emission tomography-computed tomography showed many enlarged lymph nodes around the abdominal aorta but no signs of lung or liver metastases. Color ultrasound revealed a mass located in the skeletal muscle and the results of histological biopsy revealed a poorly differentiated adenocarcinoma suspected to be distant metastases from colon cancer. Immunohistochemistry showed small woven bone components that were considered to be ossified. CONCLUSION This case reminds us that for patients with advanced colorectal tumors, we should be alert to the possibility of unconventional metastasis.
Background: Even with the augmentative application of anal-preservation surgery in low rectal cancer, the role and indications of laparoscopic intersphincteric resection (Lap ISR) are still under debate, especially for T3 or nodepositive (T3N0M0, T1-3N+M0) cancer, mainly due to the oncological safety and functional outcomes. INTRABEAM (Carl Zeiss, Germany) intraoperative radiotherapy (IORT) using low-energy X-rays features in accurate irradiation, less exposure, and reduced complications. Taking advantages of Lap ISR and INTRABEAM IORT, this innovative approach aims to increase the probability of the anal preservation with acceptable postoperative outcomes. Materials and methods: From December 2015 to August 2019, we retrospectively analyzed the short-term outcomes of 12 patients evaluated preoperatively with T3 or node-positive (T3N0M0, T1-3N+M0) primary locally advanced low rectal cancer. They all had received Lap ISR and INTRABEAM IORT with a dose of 16-18 Gy applied by an applicator through the anus (natural orifice). Then, with no pre-or postoperative radiotherapy given, the patients were suggested to receive 6-8 cycles of the XELOX chemotherapy regimen (oxaliplatin, 130 mg/m 2 and capecitabine, 1000 mg/m 2). Results: All patients achieved R0 resection. The median radiation time was 27 min and 15 s, and the mean radiative dose was 17.3 Gy (range 16-18 Gy). The median follow-up time was 18.5 months (range 3-45 months). Two patients experienced local recurrence. Two male patients experienced anastomotic stenosis. Furthermore, one of them experienced perianal abscess and the other one experienced pulmonary metastasis after refusing to receive chemotherapy. One female patient with internal anal sphincter invasion experienced distant metastases to the liver and gluteus maximus muscle 35 months after IORT. No acute radiation injuries or symptoms were observed. Although they experienced a reduction in anal function, every patient was satisfied with the postoperative outcomes.
Background Colorectal cancer (CRC), the third most commonly diagnosed malignant carcinoma and the third most common cause of carcinoma-related mortality, continues to be a major international health problem. And approximately 33% of patients suffer from recurrence after radical surgery. Free malignant cell implanting in the peritoneum is generally accepted as one of the main reasons of such outcome. We did this present clinical study with the aim of evaluating the effects and safety of intraoperative intraperitoneal chemotherapy (IOC) on patients suffering from colorectal cancer, with hoping to find a novel, effective, and available approach to deal with malignant cell implanting during surgeries. Methods In total, 391 patients who went through colorectal radical surgery were considered eligible between June 1, 2017, and December 31, 2018. 220 patients were treated with surgery without IOC, while other 171 patients received surgery plus IOC. Clinical characteristics, operative findings, postoperative short-term outcomes, disease-free survival (DFS), and overall survival (OS) were compared between these above 2 groups in the selected population. Result The present research included 391 patients (251 men and 140 women) who underwent surgery without IOC (n = 171) or surgery plus IOC (n = 220), with a mean (SD) age of 60.4 (9.7) years in the surgery without IOC group and 60.6 (8.7) in the surgery plus IOC group (P=.85). No significant differences were witnessed between the two groups in surgery-related information and postoperative complications. It is worth noting that IOC independent of other factors was associated with a favor prognosis in CRC patients with stage II/III (HR 0.50, 95%CI 0.30–0.82, P=.006). Moreover, for patients with stage II colorectal carcinoma, DFS did not differ between two groups (P=.553, Kaplan-Meier log-rank), and OS was no exception. In stage III CRC patients, the estimated DFS rate for patients receiving IOC was 82.2% and patients without IOC was 66.4% after 3 years, which demonstrated that IOC was associated with a favorable prognosis in stage III patients (P=.012, Kaplan-Meier log-rank). Furthermore, the differences were still remained between the two groups when considering the influence about postoperative chemotherapy (P=.014, Kaplan-Meier log-rank). IOC can also significantly improve patients’ overall survival whether they get treatment with POC (P=.006, Kaplan-Meier log-rank; P=.025, Kaplan-Meier log-rank). Conclusions In the present study, we have found that surgery plus IOC generated a favorable prognosis for stage III CRC patients but not stage II without any side-effects when the dosage of lobaplatin was 0.1g/L. As a new, safe, and simple procedure, IOC therapy is easily performed—and does not require any special devices or techniques. Thus, IOC is a promising and exciting therapeutic strategy for patients with CRC.
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