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PubMed2025

CS Ratio is an immune-related prognostic biomarker for cervical cancer.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in cancer progression but its complex structure significant variability among patients present considerable challenges for research. Recent studies have demonstrated that macrophage polarization states defined by the expression levels of CXCL9 SPP1 (CS Ratio) are more prognostically relevant than traditional M1/M2 markers. The CS polarization state reflects a highly coordinated network of pro-tumor anti-tumor variables offering a simplified yet effective immune response indicator for the complex TME. The CS Ratio has been shown to correlate with the abundance of anti-tumor immune cells the gene expression programs of tumor-infiltrating cells responses to immunotherapy. Cervical cancer, one of the most common gynecological malignancies, still faces limited therapeutic options. CXCL9, a member of the CXC chemokine family, plays a critical role in immune regulation, inflammation, tumor growth, angiogenesis, and metastasis. Similarly, SPP1, a cytokine, influences immune-related pathways by regulating molecules such as interferon-γ and interleukin-12. However, no studies have systematically investigated the role of the CS Ratio in cervical cancer or its relationship with immunotherapy characteristics. Research in this area could provide critical insights into the role and clinical potential of the CS Ratio in cervical cancer and related tumors. METHODS: The expression ratio of CXCL9 to SPP1 was analyzed in cervical cancer patients using data from the Gene Expression Omnibus (GEO) database, which revealed significant differences. Data for cervical cancer patients were obtained from The Cancer Genome Atlas (TCGA) database. The optimal cutoff value for the CS Ratio was determined using the maxstat package in R, and Kaplan-Meier (KM) survival curves were constructed. Patients were categorized into High and Low groups based on the median CS Ratio. Immune scores were analyzed, and immune cell infiltration was assessed using CIBERSORT. Differences in the CS Ratio were evaluated across patients with varying pathological T stages and FIGO stages. Additionally, receiver operating characteristic (ROC) analysis was performed using the pROC package in R to calculate the area under the curve (AUC). Univariate and multivariate Cox regression analyses were performed to evaluate the potential of the CS Ratio as an independent prognostic factor in cervical cancer. A Cox regression-based nomogram integrating four key features was subsequently developed for the TCGA-CESC cohort. Nomogram performance was assessed using calibration curves and ROC analysis. RESULTS: The CS Ratio was significantly lower in cervical cancer patients compared to normal controls (P < 0.05). KM survival curves indicated that patients in the CS High group exhibited better prognoses. Immune score analysis revealed significantly higher immune scores (P < 0.05) and lower tumor purity (P < 0.05)in the CS High group compared to the Low group. CIBERSORT analysis revealed significantly higher proportions of CD8+ T cells (P < 0.05) and M1 macrophages (P < 0.05), and a significantly lower proportion of M2 macrophages (P < 0.05), in the CS High group compared to the Low group. The CS Ratio significantly decreased with advancing FIGO stage (P < 0.05). Both univariate (P < 0.05) and multivariate Cox regression analyses (P < 0.05) confirmed the CS Ratio as an independent prognostic factor. ROC analysis demonstrated that the CS Ratio had higher AUC values for predicting 1-year (AUC=0.69), 3-year (AUC=0.66), and 5-year OS (AUC=0.68) than CXCL9 or SPP1 alone. The Cox regression-based nomogram integrating four key features demonstrated predictive capability for 1-, 3-, and 5-year OS in CESC patients (Concordance Index = 0.751; 95% CI: 0.678-0.824; p = 1.50Í10-11). Significant survival differences were observed between the high-risk and low-risk groups based on the nomogram score. ROC analysis yielded high AUC values for survival prediction: 0.85 (95% CI: 0.94-0.75) at 1-year, 0.74 (95% CI:0.84-0.64) at 3-year, and 0.72 (95% CI:0.84-0.61) at 5-year. CONCLUSION: The CS Ratio may serve as a more effective prognostic biomarker for cervical cancer patients.

CXCL9↗

PubMed2026

Context-Dependent cGAS-STING Activation Shapes Metastatic Progression and Dormancy.

Cancer cells survive, proliferate, and metastasize in part because the immune system fails to detect and eliminate them. Moreover, the tumor microenvironment (TME) that surrounds the tumor supports cancer cell survival and resistance to chemo- and immunotherapies by inhibiting antitumor immune responses and thereby reducing the efficacy of immunotherapeutic interventions. cGAS-STING signaling senses cytoplasmic DNA and coordinates innate immune responses that shape tumor-intrinsic outcomes and the TME. Emerging evidence reveals a context-dependent, dualistic role for cGAS-STING in metastatic progression and cancer dormancy. Acute, robust activation in antigen-presenting cells promotes type I interferon responses, leading to suppression of tumor growth. By contrast, chronic, low-level cancer-intrinsic STING signaling can engage inflammatory programs that foster immune suppression and therapy resistance. Dormant disseminated tumor cells exploit niche cues to downregulate STING signaling and evade immune detection, whereas reactivation of dormant cells often involves restoration of STING activity that can promote immune elimination. In this article, we review mechanisms linking genome instability and cytoplasmic DNA to STING activation, summarize evidence for tumor-suppressive versus tumor-promoting functions across metastatic niches, and discuss how STING agonists and combination strategies may be optimized to maximize antitumor immunity while avoiding protumorigenic effects.

Humans↗

PubMed2004

Microscopic spread of low rectal cancer in regions of mesorectum: pathologic assessment with whole-mount sections.

AIM: To assess the microscopic spread of low rectal cancer in mesorectum regions to provide pathological evidence for the necessity of total mesorectal excision (TME). METHODS: A total of 62 patients with low rectal cancer underwent low anterior resection and TME, surgical specimens were sliced transversely on the serial embedded blocks at 2.5 mm interval, and stained with hematoxylin and eosin (HE). The mesorectum on whole-mount sections was divided into three regions: outer region of mesorectum (ORM), middle region of mesorectum (MRM) and inner region of mesorectum (IRM). Microscopic metastatic foci were investigated microscopically on the sections for the metastatic mesorectal regions, frequency, types, involvement of lymphatic vessels and correlation with the original rectal cancer. RESULTS: Microscopic spread of the tumor in mesorectum and ORM was observed in 38.7% (24/62) and 25.8% (16/62) of the patients, respectively. Circumferential resection margin (CRM) with involvement of microscopic metastatic foci occurred in 6.5% (4/62) of the patients, and distal mesorectum (DMR) involved was 6.5% (4/62) with the spread extent within 3 cm of low board of the main lesions. Most (20/24) of the patients with microscopic metastasis in mesorectum were in Dukes C stage. CONCLUSION: Results of the present study support that complete excision of the mesorectum without destruction of the ORM is essential for surgical management of low rectal cancer, an optimal DMR clearance resection margin should be no less than 4 cm, further pathologic assessment of the regions in extramesorectum in the pelvis is needed.

Adenocarcinoma↗

PubMed2006

Modern management of rectal cancer: a 2006 update.

The goal of this review is to outline some of the important surgical issues surrounding the management of patients with early (T1/T2 and N0), as well as locally advanced (T3/T4 and/or N1) rectal cancer. Surgery for rectal cancer continues to develop towards the ultimate goals of improved local control and overall survival, maintaining quality of life, and preserving sphincter, genitourinary, and sexual function. Information concerning the depth of tumor penetration through the rectal wall, lymph node involvement, and presence of distant metastatic disease is of crucial importance when planning a curative rectal cancer resection. Preoperative staging is used to determine the indication for neoadjuvant therapy as well as the indication for local excision versus radical cancer resection. Local excision is likely to be curative in most patients with a primary tumor which is limited to the submucosa (T1N0M0), without high-risk features and in the absence of metastatic disease. In appropriate patients, minimally invasive procedures, such as local excision, TEM, and laparoscopic resection allow for improved patient comfort, shorter hospital stays, and earlier return to preoperative activity level. Once the tumor invades the muscularis propria (T2), radical rectal resection in acceptable operative candidates is recommended. In patients with transmural and/or node positive disease (T3/T4 and/or N1) with no distant metastases, preoperative chemoradiation followed by radical resection according to the principles of TME has become widely accepted. During the planning and conduct of a radical operation for a locally advanced rectal cancer, a number of surgical management issues are considered, including: (1) total mesorectal excision (TME); (2) autonomic nerve preservation (ANP); (3) circumferential resection margin (CRM); (4) distal resection margin; (5) sphincter preservation and options for restoration of bowel continuity; (6) laparoscopic approaches; and (7) postoperative quality of life.

Colorectal Surgery↗

PubMed2004

[Causes of local recurrence after curative surgery for rectal cancer].

The rate of local recurrence (LR) has been 20-40% after resective surgery for rectal cancer by the traditional - Miles or Dixon - operative technics. The authors performed curative resection in 358 patients with rectal cancer in a 10 year period (01.01.1990 - 31.12.2000) in the Surgical Department of Szeged University. Since 01.01.1996 the authors changed this type of surgery for the Heald technics (total mesorectal excision - TME - with sharp dissection, using the UltraCision device) for the surgical treatment of middle or lower third rectal cancer. To compare the results of the two procedures, the authors analysed their material in two periods: Period I: 01.01.1991 - 31.12.1992: 62 patients operated on with the traditional operative technics; LR 15% within 2 years after surgery. Period II: 01.01.1997 - 31.12.1998: 78 patients operated on with the Heald technics (TME with sharp dissection); LR 6.4% within 2 years after surgery. Based on their results, the authors found that the modern operative technics by Heald, used in the second period of the study, was a relevant factor decreasing LR from 15% to 6.4%, while the gender, age of the patients, ratio of the abdominoperineal extirpation versus anterior resection (APRE/AR) and the free margin of more than 3 cm proved to be irrelevant.

Age Factors↗

PubMed2000

[Total excision of the mesorectum].

In retrospective study authors present early results after the introduction of total mesorectal excision (TME) in rectal cancer surgery. In the period (1995-1998) 50 patients had low anterior resection. Of these 33 were performed with total mesorectal excision. 28 of 33 patients had curative resection, 5 patients had palliative resection due to hepatic metastases. Postoperative mortality rate in TME group was 12% due to cardiac disease. The rate of anastomostic failure was 6%. During minimally 2 years follow-up in 15 patients, local recurrence as well as distant metastases had developed in 1 patient (6.6%) respectively.

Aged↗

PubMed2000

[Improved therapeutic results in rectal cancer. Preoperative radiotherapy and continuing education of the surgeons is efficient].

The aim of the Stockholm Colorectal Cancer Study Group is to improve treatment results in colorectal cancer. Between 1980 and 1993 the group conducted two randomised trials on preoperative radiotherapy in rectal cancer including 1406 patients. In both trials radiotherapy significantly reduced local recurrence and improved cancer specific survival. To further improve treatment results, four workshops have been held to introduce the "TME concept" to surgeons in Stockholm. The workshops included live surgical demonstrations and histopathology sessions. When patients included in the Stockholm trials (1980-1993) were compared to patients included in the "TME project" (1995-1996) the rate of abdominoperineal procedures was reduced from 60 to 27 per cent. Within two years of follow up the local recurrence rate was reduced from 15 to 6 per cent and cancer related deaths from 16 to 9 per cent. It is concluded that surgical teaching initiatives may have a significant impact on cancer outcomes.

Clinical Competence↗

PubMed2000

[Historical review of colorectal cancer surgery].

The classical standard surgical technique for rectal carcinoma, abdominoperineal excision (Miles operation), has been gradually replaced by sphincter-saving surgery and more than 70% of rectal carcinomas are treated by anterior resection in which autosuture machines have played a major role in recent years. Wide lateral lymphadenectomy has been replaced by autonomic nerve preservation because of the high frequency of sexual and urinary dysfunction. Total mesorectal excision (TME) proposed by Heald et al which ignores the lateral nodes of the pelvic wall is the most popular technique in Western countries. The concept of TME is contradictory to that of wide lateral lymphadenectomy and the true merits of the latter should be examined in the near future. Minimally invasive surgery, including various procedures of local excision of low rectal tumors and colonoscopic polypectomy, has given great benefits to many patients. In Japan there seems to have been a lack of interest in adjuvant radiotherapy and chemoradiotherapy in the past, but they should be more seriously considered for the adjuvant treatment of advanced rectal carcinoma in the future.

Colonoscopy↗

PubMedDate not supplied

Total mesorectal excision in the treatment of rectal cancer: a review.

Despite the improvements in preoperative staging, surgical technique and adjuvant therapy, local recurrence remains a significant problem in rectal cancer surgery. Several patient- and tumour-related risk factors for the development of local recurrence have been identified and are being addressed by regimens of pre- or postoperative adjuvant therapy. Total mesorectal excision (TME) recently has been shown to result in a low recurrence rate even without the use of adjuvant therapy. Nevertheless, conclusive evidence in the form of a prospective randomized trial is to date not available. This paper describes the technique of TME and reviews the clinical and pathological data supporting its use in rectal cancer surgery.

Digestive System Surgical Procedures↗

PubMed2001

[Recurrence and survival after conventional low anterior resection for rectal cancer].

INTRODUCTION: The aim of the study was to evaluate the incidence of recurrence of local cancer, distant metastases and survival after conventional low anterior resection for cure in patients with rectal carcinoma, on the basis of the poor prognosis after colorectal cancer in Denmark. MATERIAL AND METHODS: Consecutive patients operated on in the nine Danish departments of surgical gastroenterology in 1992-1993. Retrospective collection of data on recurrence of local cancer, distant metastases, and over-all survival at the end of 1996. RESULTS: Of 268 patients, 77 (29%) developed recurrent local cancer and/or distant metastases. Forty-eight (18%) had local recurrence with a cumulative 5-year rate of 39%. Distant metastases were seen in 54 (20%). The local recurrence rate increased with increasing Dukes' tumour stage and was higher after operation by a non-specialist (30%) than by a consultant, another specialist, or a surgeon under training and supervised by a consultant (15-17%) (p = 0.04). Multiple regression showed that the recurrence rate was independent of tumour localisation, blood loss, transfusion, anastomotic leakage, and status of the surgeon. The cumulative crude 5-year survival was 50% and independent of the status of the surgeon. DISCUSSION: Our relatively high local recurrence rate and the results in the literature after total mesorectal excision (TME) indicate that the conventional technique should be replaced by TME, which has become the recommended method in recent years. Furthermore, we propose a changed strategy in the treatment of rectal cancer. The patients should be treated in fewer departments with established teams of rectal cancer specialists taking part in all operations for rectal cancer.

Adenocarcinoma↗

PubMed2000

[Utilizable value of wild economic plant resource--acron kernel].

Peking whites breeding hens were selected. Using true metabolizable energy method (TME) to evaluate the available nutritive value of acorn kernel, while maize and rice were used as control. The results showed that the contents of gross energy (GE), apparent metabolizable energy (AME), true metabolizable energy (TME) and crude protein (CP) in the acorn kernel were 16.53 mg/kg-1, 11.13 mg.kg-1, 11.66 mg.kg-1 and 10.63%, respectively. The apparent availability and true availability of crude protein were 45.55% and 49.83%. The gross content of 17 amino acids, essential amino acids and semiessential amino acids were 9.23% and 4.84%. The true availability of amino acid and the content of true available amino acid were 60.85% and 6.09%. The contents of tannin and hydrocyanic acid were 4.55% and 0.98% in acorn kernel. The available nutritive value of acorn kernel is similar to maize or slightly lower, but slightly higher than that of rice. Acorn kernel is a wild economic plant resource to exploit and utilize but it contains higher tannin and hydrocyanic acid.

Amino Acids↗

PubMed2003

[On rationality of total mesorectal excision for rectal cancer].

OBJECTIVE: To discuss the rationality and clinical significance of total mesorectal excision (TME) assessed by the pattern of local recurrence of rectal cancer. METHODS: 207 rectal cancer patients treated by surgery from 1975 to 2001 who developed local recurrence were retrospectively studied as to the option of treatment based on their outcome. 172 of these 207 patients had complete record of follow-up with a follow-up rate of 83.0%. RESULTS: The local recurrent sites of 207 patients were: anastomotic stoma 71, mesorectum 65, perineum 50, lymph nodes 59, multiple recurrences 89 and others sites rare. Among 81 patients who had been first treated by anterior resection (AR), 58 were again treated by abdomino-perineal resection (APR). Among 102 patients who had been treated by APR, 38 were treated by perineal tumor resection, 15 were treated by total and posterior pelvic organ resection, and 18 were supplemented with lymph node resection. By all modalities, the resection rate was 66.1% (137/207), in which the curable resection rate was 46% (63/137). The 5-year survival rate of patients with tumor resection was 23.3% (32/137), those treated by curable resection was 34.9% (22/63). CONCLUSION: From the pattern of local recurrence, the operation for middle-lower rectal cancer must follow the principle of total mesorectum excision (TME). Patients with local recurrence should be energetically treated in the second operation if tolerable.

Adenocarcinoma↗

PubMed1977

Observation on the remarkable stability of transmissible mink encephalopathy virus.

Transmissible mink encephalopathy (TME) virus retained biological activity after prolonged storage in formalin (about three and a half years) and in paraffin tissue blocks used for histologic preparations (about six and a half years). Thus, TME tissues in formalin and in paraffin blocks should be handled as contaminated materials.

Animals↗

PubMed2003

Advances in surgical treatment of rectal cancer.

UNLABELLED: Increased understanding of the natural history of the disease, standardization of surgery and new procedures have led to significant advances in the treatment of rectal cancer. Anatomical dissection of the mesorectum permits optimal local control and volume cases may further improve oncological RESULTS: Autonomic pelvic nerves are preserved by the technique of total mesorectal excision (TME) and adapted anterior dissection plans improve preservation of genito-urinary functions. Sphincter preservation can be achieved by a conventional anterior resection for high and mid-rectal tumours, and by the technique of intersphincteric resection for low tumours. A J-pouch or a recently-designed coloplasty pouch must be associated with coloanal anastomoses in order to improve functional results and loop ileostomy is recommended to decrease early postoperative morbidity. Local excision constitutes an alternative to major surgery in patients with a low-risk early rectal cancer. Neoadjuvant treatments have a role in local control of the disease after TME surgery and in new strategies of sphincter-saving procedures. The place of anorectal reconstruction and that of laparoscopy are also discussed.

Adenocarcinoma↗

PubMedDate not supplied

Underlying anatomy for CTV contouring and lymphatic drainage in rectal cancer radiation therapy.

Despite the low local recurrence rate that can be achieved by adequate surgery (total mesorectal excision--TME), radiation therapy was shown to play a significant role in reducing this risk. The widespread use of TME in many European Centers has introduced a new terminology and the need to identify the area at major risk for local failure using this surgical procedure. In the surgical series where extended extra-mesorectal surgery was performed, the role of lymphatic spread was evidenced, especially for low rectal cancer, through the pelvic parietal fascia and lateral pelvic spaces. The aim of this study was to better define some anatomic concepts and the main risk factors which impact on CTV contouring and field conformation in rectal cancer treatment. This information helps formulating guidelines for CTV contouring in daily radiotherapy practice, in order to define the best therapy, according to the tumor stage and location.

Combined Modality Therapy↗

PubMed2003

The rational principles of neo-adjuvant therapy for rectal cancer.

BACKGROUND: Aim of the study is to analyze rational principles which at present govern the neoadjuvant therapy for rectal cancer and justify his application. First step is definition of targets: cellular replication block, volumetric reduction of rectal cancer, mesorectum and lateral nodes (Down staging), reduction of side-effects on close organs, radiation on more limited tissue volumes, major series of sphincter saving procedures, minor risk of microscopic tumour deposits. Second step regards standards which Protocols strive in order to: patients selection, therapeutic index, restaging before surgery, total mesorectal excision (TME). Further step accounts for evidence of drawbacks, related to Neoadjuvant approach, both Radiotherapy alone (RT) or Radiochemotherapy (CH-RT). METHODS: Indications for neoadjuvant therapy, basing a difference between the absolute and relative one, are explained. Given that granting role to such therapy still now remain partially unclear, we have outlined the following topics: A) survey of main protocols is managed, taking care on dose/response ratio, focusing on enhanced supply for fixed tumours, checking on a list of several drugs (oxaliplatinum, capecitabin, raltitrexed, CPT-11, eniluracil), which are medicated with RT and furthermore on a list of substitute RT methods (HART, IORT, Endocavitary). B) following whole treatments, according such a different approaches, analysis of obtained outcomes in the literature are carried out. C) Personal experience, basing on a previous series where Down-staging has been sought, comparing indicatively clinical and diagnostic data before neoadjuvant therapy and before surgery. D) List of open issues, not solved at present, is shown CONCLUSIONS: Neoadjuvant therapy may be considered a rational approach for treatment of curative rectal cancer; indeed, preliminary results seem to introduce a real advantage compared to adjuvant therapy, even if is mandatory to associate proper surgical procedure, as TME, to warrant low local recurrences. Targets, related to such therapy, may be noticed ideal even though outcomes don't come up always to statements. So, continuous efforts to ameliorate rates of free-disease series, as well mortality rates and toxical effects are advised.

Chemotherapy, Adjuvant↗

PubMed2004

[Colorectal cancer: what should be the management of primary tumour?].

Colon and rectal cancer are in France a challenging problem in public health, reaching the second place in cancer related deaths. Surgery is still the key of curative treatment. Crude survival increased from 33% to 55% during twenty years. Colonoscopy is the referent exam for positive diagnosis. In rectal cancer, endorectal ultrasound and MRI have optimised local staging. The quality of general staging is important since it could change therapeutic strategy. Spiral CT scan is now probably superior to conventional ultrasound in the detection of liver metastases. Laparotomy is still the standard surgical approach. Main prospective studies in the evaluation of laparoscopic approach are still ongoing. Rectal resection for cancer is today a standardised procedure: total mesorectal excision (TME) should be done for rectal tumours below peritoneal reflection; TME decreases both the risk of local recurrence and the frequency of urogenital sequelae. The quality of surgical resection for colorectal cancer should always be checked and particularly, the number of lymph nodes, the longitudinal and lateral margins for rectal cancer, and resection for fixed tumours. Adjuvant chemotherapy with 5 fluorouracil and folinic acid is a standard for UICC stage III patients, but with a clearer benefit for colon tumours. Preoperative irradiation for T3-T4 rectal tumours is an European standard, providing a better local control; irradiation could also improved survival. In the oncoming years, surgeon and hospital specialization will probably be the main factor of progress in the management of colorectal cancer in France.

Antimetabolites, Antineoplastic↗

PubMed2004

[Rectal cancer--review of methods and treatment results].

Rectal cancer poses a significant worldwide problem. Until the late 19 century surgeons were convinced that surgical attempts of treating rectal cancers were doomed to failure. Currently, surgery is associated with a poor prognosis, a high likelihood of permanent colostomy and a high rate of local recurrence in patients with regional disease. Functional changes such as bladder dysfunction and impotence remain distressingly common consequences of conventional surgery. An important understanding of rectal cancer pathology allied to modern surgical techniques such as intestinal stapling guns has led to an increased number of sphincter saving operations. The technique of sharp dissection along definable planes known as total mesorectal excision (TME) produces the complete resection of an intact package of the rectum and surrounding mesorectum, enveloped within the visceral pelvic fascia with uninvolved circumferential margins. As a result of TME, 5-year survival figures have risen from 45-50% to 78%, local recurrence rates have declined from 30% to 5-8%, sphincter preservation has risen by at least 20%, and the rates of bladder dysfunction and impotence have declined from 50-70% to 15%. In some selected cases transanal techniques with or without radiotherapy have improved the success of local excision. The value of laparoscopic surgery for rectal cancer in terms of cancer outcome can only be assessed by large clinical trials with sufficient follow-up.

Digestive System Surgical Procedures↗