Objective To explore the effects of miR-373 and Janus kinase 2/signal transducer and activator of transcription 6 (JAK2/STAT6) signaling pathways on the M2 polarization of tumor associated macrophages (TAM) in rectal cancer. Methods THP-1 cells were induced into M0/M1/M2 macrophages, M0 macrophages were cocultured with Caco-2 cells to obtain TAM, Flow cytometry was used to detect the expression of CD86 and CD206, Real-time quantitative qPCR and Western blot were used to detect miR-373, inducible nitric oxide synthase (iNOS), toll-like receptor 4 (TLR-4), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), arginase 1 (Arg1), chitinase 3-like 1 (Ym1), resistin like α (Fizz1), IL-10 mRNA and protein levels. TAM were transfected and divided into overexpressing miR-373 group (miR-373-TAM) and control group (miR-NC-TAM), overexpressing miR-373+JAK2-TAM group (miR-373 combined with JAK2-TAM) and control group (miR-373 combined with NC-TAM), and then cocultured with Caco-2 cells. Flow cytometry was used to detect the expression of CD206 in TAM; Real-time quantitative PCR and Western blot were used to detect miR-373, Arg1, Ym1, Fizz1, IL-10, JAK2, STAT6 mRNA and protein levels in TAM; CCK-8 assay, colony formation assay, and Transwell assay were used to detect the proliferation, migration, and invasion ability of Caco-2 cells. Thirty nude mice were randomly divided into Caco-2 cells group, Caco-2 cells combined with miR-NC-TAM group, and Caco-2 cells combined with miR-373-TAM group, with 10 mice in each group. Rats in each group were subcutaneously injected with pure Caco-2 cells, Caco-2 cells combined with TAM, and Caco-2 cells combined with TAM overexpressing miR-373. After 4 weeks of cell inoculation, immunofluorescence staining was used to detect F4/80⁺CD206⁺cells level in tumor tissue; Real-time quantitative PCR and Western blot were used to detect miR-373, JAK2, STAT6, Arg1, Ym1, Fizz1, IL-10 mRNA and protein levels in tumor tissues. Results TAM tended to M2 polarization. After overexpression of miR-373, miR-373 level in TAM was increased, while Arg1, Ym1, Fizz1, IL-10, JAK2, STAT6 mRNA and protein levels were decreased, proliferation, migration, invasion ability of Caco-2 cells were decreased; Overexpression of JAK2 could partially reverse the effect of overexpression of miR-373 on the M2 polarization of TAM and proliferation, migration, invasion ability of Caco-2 cells. TAM could promote tumor growth; Overexpression of miR-373 could inhibit tumor growth and inhibit M2 polarization of TAM. Conclusion miR-373 could inhibit M2 polarization of TAM in rectal cancer, and miR-373 might inhibit proliferation and metastasis of rectal cancer cells by regulating the JAK2/STAT6 pathway.
MicroRNAs/metabolism* ; Humans ; STAT6 Transcription Factor/genetics* ; Signal Transduction/genetics* ; Animals ; Janus Kinase 2/genetics* ; Mice ; Tumor-Associated Macrophages/metabolism* ; Rectal Neoplasms/pathology* ; Caco-2 Cells ; Mice, Nude ; THP-1 Cells ; Mice, Inbred BALB C ; Cell Polarity ; Male

The lungs are the most common sites of metastases from non-pulmonarymalignancies. Endobronchial metastases are rare and have no specificity in clinical manifestations,thus being prone to misdiagnosis and delayed treatment.The common tumors associated with endobronchial metastasis are renal,breast,and colorectal cancers.This article reported one case of postoperative rectal cancer with endobronchial and lung metastases,which was relieved by high-frequency electrocautery ablation via bronchoscope,chemotherapy,and targeted drugs,aiming to provide a reference for clinical diagnosis and treatment.
Humans ; Rectal Neoplasms/pathology* ; Electrocoagulation/methods* ; Bronchial Neoplasms/drug therapy* ; Bronchoscopy ; Lung Neoplasms/secondary* ; Bronchoscopes

Occult breast cancer (OBC) refers to a type of breast cancer where no primary lesion is detected through physical examination, imaging, and pathology. This report presents a clinical case of OBC with intestinal obstruction as the initial symptom. A 67-year-old female with no underlying conditions presented to Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University with intestinal obstruction. Contrast-enhanced CT of the abdomen showed thickening of the lower rectum and ascending colon, suggestive of a neoplastic lesion. Chest CT showed multiple enlarged lymph nodes in the left axilla. Colonoscopy revealed only mucosal congestion, roughness, and thickening. Suspecting an intestinal tumor, laparoscopic radical resection of the rectal stenosis was performed. Postoperative pathology indicated poorly differentiated adenocarcinoma of the rectum. Immunohistochemistry showed positive expression of estrogen receptor (ER), progesterone receptor (PR), GATA-binding protein 3 (GATA3), and cytokeratin 7 (CK7), suggesting breast cancer metastasis. Breast MRI revealed multiple proliferative nodules in both breasts (breast imaging reporting and data system, BI-RADS 2). Biopsies of the right lower-inner breast, bilateral axillary, and supraclavicular lymph nodes were performed. No carcinoma was found in the right breast tissues; however, small foci of carcinoma was detected in the right axillary lymph nodes, and poorly differentiated carcinoma of suspected breast origin was found in the bilateral supraclavicular and left axillary lymph nodes. The final diagnosis was OBC with lymph node and rectal metastasis. The patient died 16 months postoperatively. OBC often lacks identifiable primary breast lesions, and gastrointestinal metastases are particularly rare. Clinical manifestations are frequently masked by symptoms of metastatic lesions, making diagnosis challenging. Clinicians should maintain a high index of suspicion. Due to rapid disease progression and multiorgan involvement, prognosis is extremely poor. Early identification of the primary lesion in OBC is crucial for improving outcomes.
Humans ; Female ; Aged ; Intestinal Obstruction/etiology* ; Breast Neoplasms/pathology* ; Adenocarcinoma/diagnosis* ; Neoplasms, Unknown Primary/complications* ; Rectal Neoplasms/complications*

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Objective: To investigate the clinicopathological features, immunophenotype, and genetic alterations of rectal adenocarcinoma with enteroblastic differentiation. Methods: Four cases of rectal adenocarcinoma with enteroblastic differentiation were collected at the Affiliated Hospital of Qingdao University, Qingdao, China (three cases) and Yantai Yeda Hospital of Shandong Province, China (one case) from January to December 2022. Their clinical features were summarized. Hematoxylin and eosin stain and immunohistochemical stain were performed, while next-generation sequencing was performed to reveal the genetic alterations of these cases. Results: All four patients were male with a median age of 65.5 years. The clinical manifestations were changes of stool characteristics, bloody stools and weight loss. All cases showed mixed morphology composed of conventional adenocarcinoma and adenocarcinoma with enteroblastic differentiation. Most of the tumors consisted of glands with tubular and cribriform features. In one case, almost all tumor cells were arranged in papillary structures. The tumor cells with enteroblastic differentiation were columnar, with relatively distinct cell boundaries and characteristic abundant clear cytoplasm, forming fetal gut-like glands. Immunohistochemically, the tumor cells were positive for SALL4 (4/4), Glypican-3 (3/4) and AFP (1/4, focally positive), while p53 stain showed mutated type in 2 cases. The next-generation sequencing revealed that 2 cases had TP53 gene mutation and 1 case had KRAS gene mutation. Conclusions: Rectal adenocarcinoma with enteroblastic differentiation is rare. It shows embryonal differentiation in morphology and immunohistochemistry, and should be distinguished from conventional colorectal adenocarcinoma.
Humans ; Male ; Aged ; Female ; Biomarkers, Tumor/metabolism* ; Adenocarcinoma/pathology* ; Colorectal Neoplasms ; Rectal Neoplasms/genetics* ; Cell Differentiation

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

After the implementation of neoadjuvant chemoradiotherapy and total mesorectal excision, lateral local recurrence becomes the major type of local recurrence after surgery in rectal cancer. Most lateral recurrence develops from enlarged lateral lymph nodes on an initial imaging study. Evidence is accumulating to support the combined use of neoadjuvant chemoradiotherapy and lateral lymph node dissection. The accuracy of diagnosing lateral lymph node metastasis remains poor. The size of lateral lymph nodes is still the most commonly used variable with the most consistent accuracy and the cut-off value ranging from 5 to 8 mm on short axis. The morphological features, differentiation of the primary tumor, circumferential margin, extramural venous invasion, and response to chemoradiotherapy are among other risk factors to predict lateral lymph node metastasis. Planning multiple disciplinary treatment strategies for patients with suspected nodes must consider both the risk of local recurrence and distant metastasis. Total neoadjuvant chemoradiotherapy is the most promising regimen for patients with a high risk of recurrence. Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy seemingly improves the local control of positive lateral nodes. However, its impact on the safety of surgery in patients with no response to the treatment or regrowth of lateral nodes remains unclear. For patients with smaller nodes below the cut-off value or shrunken nodes after treatment, a close follow-up strategy must be performed to detect the recurrence early and perform a salvage surgery. For patients with stratified lateral lymph node metastasis risks, plans containing different multiple disciplinary treatments must be carefully designed for long-term survival and better quality of life.
Humans ; Lymphatic Metastasis/pathology* ; Quality of Life ; Neoplasm Staging ; Retrospective Studies ; Lymph Nodes/pathology* ; Rectal Neoplasms/surgery* ; Lymph Node Excision/methods* ; Neoadjuvant Therapy/methods* ; Neoplasm Recurrence, Local/surgery*

Objective: To investigate the factors influencing tumor-specific survival of early-onset locally advanced rectal cancer. Methods: All-age patients with primary locally advanced rectal cancer from the Surveillance, Epidemiology, and End Results (SEER) database (2010 to 2019) were included in this study. Early- and late-onset locally advanced rectal cancer was defined according to age of 50 years at diagnosis. Early-onset locally advanced rectal cancer was divided into five age groups for subgroup analyses. Age, sex, tumor-specific survival time and survival status of patients at diagnosis, pathological grade, TNM stage, perineural invasion, tumor deposits, tumor size, pretreatment CEA , radiotherapy, chemotherapy, and number of lymph node dissections were included. Progression-free survival (PFS) was analyzed and compared between patients with early- and late-onset rectal cancer. Results: A total of 5,048 patients with locally advanced rectal cancer were included in the study (aged 27-70 years): 1,290 (25.55%) patients with early-onset rectal cancer and 3,758 (74.45%) patients with late-onset rectal cancer. Patients with early-onset rectal cancer had a higher rate of perineural invasion (P<0.001), more positive lymph nodes dissected (P<0.001), higher positive lymph node ratios (P<0.001), and a higher proportion receiving preoperative radiotherapy (P=0.002). Patients with early-onset rectal cancer had slightly better short-term survival than those with late-onset rectal cancer (median (IQR ): 54 (33-83) vs 50 (31-79) months, χ²=5.192, P=0.023). Multivariate Cox regression for all patients with locally advanced rectal cancer showed that age (P=0.008), grade of tumor differentiation (P=0.002), pretreatment CEA (P=0.008), perineural invasion (P=0.021), positive number (P=0.004) and positive ratio (P=0.001) of dissected lymph nodes, and sequence of surgery and radiotherapy (P=0.005) influenced PFS. This suggests that the Cox regression results for all patients may not be applicable to patients with early-onset cancer. Cox analysis showed tumor differentiation grade (patients with low differentiation had a higher risk of death, P=0.027), TNM stage (stage III patients had a higher risk of death, P=0.025), T stage (higher risk of death in stage T4, P<0.001), pretreatment CEA (P=0.002), perineural invasion (P<0.001), tumor deposits (P=0.005), number of dissected lymph nodes (patients with removal of 12-20 lymph nodes had a lower risk of death, P<0.001), and positive number of dissected lymph nodes (P<0.001) were independent factors influencing PFS of patients with early-onset locally advanced rectal cancer. Conclusion: Patients with early-onset locally advanced rectal cancer were more likely to have adverse prognostic factors, but an adequate number of lymph node dissections (12-20) resulted in better survival outcomes.
Humans ; Prognosis ; Retrospective Studies ; Neoplasm Staging ; Extranodal Extension/pathology* ; Survival Analysis ; Rectal Neoplasms/surgery* ; Lymph Nodes/pathology*

The treatment of locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC) has been a difficulty and challenge in the field of advanced rectal cancer, while pelvic exenteration (PE), as an important way to potentially achieve radical treatment of LARC and LRRC, has been shown to significantly improve the long-term prognosis of patients. The implementation of PE surgery requires precise assessment of the extent of invasion of LARC or LRRC and adequate preoperative preparation through multidisciplinary consultation before surgery. The lateral pelvis involves numerous tissues, blood vessels, and nerves, and resection is most difficult, and the ureteral and Marcille triangle approaches are recommended; while the supine transabdominal approach combined with intraoperative change to the prone jacket position facilitates adequate exposure of the surgical field and enables precise overall resection of the bony pelvis and pelvic floor muscle groups invaded by the tumor. Empty pelvic syndrome has always been an major problem to be solved during PE. The application of extracellular matrix biological mesh to reconstruct pelvic floor defects and isolate the abdominopelvic cavity is expected to reduce postoperative pelvic floor related complications. Reconstruction of the urinary system and important vessels after PE is essential, and the selection of appropriate reconstruction methods helps to improve the patient's postoperative quality of life, while more new methods are also being continuously explored.
Humans ; Pelvic Exenteration/adverse effects* ; Quality of Life ; Neoplasm Recurrence, Local/surgery* ; Pelvis/pathology* ; Postoperative Complications/etiology* ; Rectal Neoplasms/pathology* ; Retrospective Studies ; Treatment Outcome

Objective: To investigate the value of reconstruction of pelvic floor with biological products to prevent and treat empty pelvic syndrome after pelvic exenteration (PE) for locally advanced or recurrent rectal cancer. Methods: This was a descriptive study of data of 56 patients with locally advanced or locally recurrent rectal cancer without or with limited extra-pelvic metastases who had undergone PE and pelvic floor reconstruction using basement membrane biologic products to separate the abdominal and pelvic cavities in the Department of Anorectal Surgery of the Second Affiliated Hospital of Naval Military Medical University from November 2021 to May 2022. The extent of surgery was divided into two categories: mainly inside the pelvis (41 patients) and including pelvic wall resection (15 patients). In all procedures, basement membrane biologic products were used to reconstruct the pelvic floor and separate the abdominal and pelvic cavities. The procedures included a transperitoneal approach, in which biologic products were used to cover the retroperitoneal defect and the pelvic entrance from the Treitz ligament to the sacral promontory and sutured to the lateral peritoneum, the peritoneal margin of the retained organs in the anterior pelvis, or the pubic arch and pubic symphysis; and a sacrococcygeal approach in which biologic products were used to reconstruct the defect in the pelvic muscle-sacral plane. Variables assessed included patients' baseline information (including sex, age, history of preoperative radiotherapy, recurrence or primary, and extra-pelvic metastases), surgery-related variables (including extent of organ resection, operative time, intraoperative bleeding, and tissue restoration), post-operative recovery (time to recovery of bowel function and time to recovery from empty pelvic syndrome), complications, and findings on follow-up. Postoperative complications were graded using the Clavien-Dindo classification. Results: The median age of the 41 patients whose surgery was mainly inside the pelvis was 57 (31-82) years. The patients comprised 25 men and 16 women. Of these 41 patients, 23 had locally advanced disease and 18 had locally recurrent disease; 32 had a history of chemotherapy/immunotherapy/targeted therapy and 24 of radiation therapy. Among these patients, the median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to resolution of empty pelvic syndrome were 440 (240-1020) minutes, 650 (200-4000) ml, 3 (1-9) days, and 14 (5-105) days, respectively. As for postoperative complications, 37 patients had Clavien-Dindo < grade III and four had ≥ grade III complications. One patient died of multiple organ failure 7 days after surgery, two underwent second surgeries because of massive bleeding from their pelvic floor wounds, and one was successfully resuscitated from respiratory failure. In contrast, the median age of the 15 patients whose procedure included combined pelvic and pelvic wall resection was 61 (43-76) years, they comprised eight men and seven women, four had locally advanced disease and 11 had locally recurrent disease. All had a history of chemotherapy/ immunotherapy and 13 had a history of radiation therapy. The median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to relief of empty pelvic syndrome were 600 (360-960) minutes, 1600 (400-4000) ml, 3 (2-7) days, and 68 (7-120) days, respectively, in this subgroup of patients. Twelve of these patients had Clavien-Dindo < grade III and three had ≥ grade III postoperative complications. Follow-up was until 31 October 2022 or death; the median follow-up time was 9 (5-12) months. One patient in this group died 3 months after surgery because of rapid tumor progression. The remaining 54 patients have survived to date and no local recurrences have been detected at the surgical site. Conclusion: The use of basement membrane biologic products for pelvic floor reconstruction and separation of the abdominal and pelvic cavities during PE for locally advanced or recurrent rectal cancer is safe, effective, and feasible. It improves the perioperative safety of PE and warrants more implementation.
Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Pelvic Exenteration ; Biological Products/therapeutic use* ; Pelvic Floor/pathology* ; Neoplasm Recurrence, Local/surgery* ; Rectal Neoplasms/surgery* ; Postoperative Complications/prevention & control* ; Retrospective Studies ; Treatment Outcome