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PubMed2005

Breaking an absolute species barrier: transgenic mice expressing the mink PrP gene are susceptible to transmissible mink encephalopathy.

Transmissible mink encephalopathy (TME) is a rare disease of the North American mink, which has never been successfully transmitted to laboratory mice. We generated transgenic mice expressing the mink prion protein (PrP) and inoculated them with TME or the mouse-adapted scrapie strain 79A. TME infected mink PrP-transgenic mice on a murine PrP knockout background. The absolute species barrier between the infectious agent of TME and mice was therefore broken. Following TME and 79A infection of mice carrying both mink and murine PrP(C), only proteinase-resistant PrP homologous to the incoming agent was detectable. The presence of the murine PrP(C) prolonged the incubation time of TME substantially.

Animals↗
PubMed2004

Transmission of transmissible mink encephalopathy to raccoons (Procyon lotor) by intracerebral inoculation.

To determine the transmissibility of transmissible mink encephalopathy (TME) agent to raccoons and to provide information about clinical course, lesions, and suitability of currently used diagnostic procedures for detection of transmissible spongiform encephalopathies (TSEs) in raccoons, 4 raccoon kits were inoculated intracerebrally with a brain suspension from mink experimentally infected with TME. One uninoculated raccoon kit served as a control. All 4 animals in the TME-inoculated group showed clinical signs of neurologic disorder and were euthanized between 21 and 23 weeks postinoculation (PI). Necropsy examinations revealed no gross lesions. Spongiform encephalopathy was observed by light microscopy, and the presence of protease-resistant prion protein (PrPres) was detected by immunohistochemistry and Western blot techniques. Scrapie-associated fibrils were observed by negative-stain electron microscopy in the brains of 3 of the 4 inoculated raccoons. These findings confirm that TME is experimentally transmissible to raccoons and that diagnostic techniques currently used for TSE in livestock detect prion protein in raccoon tissue. According to previously published data, the incubation period of sheep scrapie in raccoons is 2 years, whereas chronic wasting disease (CWD) had not shown transmission after 3 years of observation. Because incubation periods for the 3 US TSEs (scrapie, TME, and CWD) in raccoons appear to be markedly different, it may be possible to use raccoons for differentiating unknown TSE agents. Retrospective genotyping of raccoons using frozen spleens showed that the raccoon PrP gene is identical to the mink gene at codons 179 and 224. Further studies, such as the incubation periods of bovine spongiform encephalopathy and other isolates of scrapie, CWD, and TME in raccoons, are needed before the model can be further characterized for differentiation of TSE agents.

Animals↗
PubMed2026

A pan-cancer single-cell atlas uncovers the role of sex hormones and chromosomes in sex-divergent reprogramming of the tumor microenvironment.

BACKGROUND: Sex bias is pervasive in tumors; however, how sex chromosomes and hormone-responsive signaling shape the tumor microenvironment (TME) remains insufficiently characterized. Considering the critical impact of the TME on tumor progression and response to immunotherapy, a pan-cancer investigation of sex-specific and cancer-context-dependent TME features is warranted. METHOD: Based on stringent inclusion criteria, we constructed a high-resolution pan-cancer single-cell sequencing atlas by integrating 31 publicly available single-cell RNA-seq datasets, comprising a total of 1,831,436 cells by integrating 468 samples from eight types of non-sex-specific solid tumors (282 males and 186 females). After correcting for batch effects, we identified major and minor cellular subsets. Multiple computational approaches were applied to investigate sex-associated differences in cellular composition, gene expression, pathway activity, malignant cell states and intercellular communication. RESULTS: We systematically compared sex-specific TME features across eight common solid malignancies. Male-biased CD8+ T cell exhaustion emerged as a recurrent but non-uniform feature, with its magnitude varying across cancer types and being modified by tissue-specific contexts. This pattern was associated with androgen-response signature scores and expression-based loss of the Y chromosome (LOY) scores. M2-like macrophage polarization showed a more cancer-type-dependent pattern; although female-biased enrichment was observed in selected malignancies, it did not represent a uniform pan-cancer feature. Expression-based X chromosome inactivation (XCI)/XCI escape-related programs, estrogen-response signature scores and stromal components, including fibroblasts and endothelial cells, were associated with macrophage and immune-regulatory states in specific tumor contexts. Tumor cells of male origin displayed higher genomic instability and more aggressive phenotypes, with androgen-response signatures and LOY contributing to the development of a male biased malignant state. Furthermore, expression-based LOY scores in malignant cells were associated with CD8+ T cell exhaustion based on transcriptomic proxies. CONCLUSION: Our study uncovers extensive but heterogeneous sex-specific differences in the TME across multiple cancer types. We propose a regulatory framework linking sex chromosomes, hormone-responsive signaling and TME interactions, which is consistent with recurrent male-biased CD8⁺ T cell exhaustion and context-dependent M2-like macrophage polarization. Importantly, the magnitude and, in some cancers, the direction of these sex-biased features are modified by tissue-specific contexts. These findings underscore the need to include sex chromosome and hormone status as essential biological variables in studies of the tumor microenvironment and the design of immunotherapies.

Tumor Microenvironment↗
PubMed2025

Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with the tumor microenvironment (TME) playing a pivotal role in its progression and therapeutic resistance. The ubiquitin-proteasome system (UPS), a central regulator of intracellular protein degradation, is increasingly recognized for its involvement in cancer pathogenesis, though its specific role in modulating the CRC TME remains to be fully elucidated. This review aims to systematically summarize current evidence on how the UPS influences the immunosuppressive network within the CRC TME and to evaluate its potential as a therapeutic target. METHODS: We conducted a comprehensive literature search in PubMed, Web of Science, and Scopus databases for original research articles and reviews published between January 2010 and August 2025, using keywords including "ubiquitin-proteasome system," "colorectal cancer," "tumor microenvironment,""immune escape,"and "targeted therapy." Studies were selected based on their relevance to UPS-mediated regulatory mechanisms in CRC TME remodeling, immune cell function, and treatment response. RESULTS: Our analysis of preclinical and clinical evidence reveals that the UPS critically regulates immune evasion in CRC through multiple mechanisms: (1) USP14 stabilizes indoleamine 2,3-dioxygenase 1 (IDO1), enhancing tryptophan catabolism and kynurenine accumulation, which suppresses T-cell activity; (2) E3 ligases including SPOP, C-Cbl, KLHL22, and FBW7 modulate PD-L1/PD-1 protein stability via ubiquitination, thereby influencing immune checkpoint signaling; and (3) ZFP91 facilitates K63-linked ubiquitination of PP2Ac, impairing mTORC1-mediated glycolysis in T cells and reinforcing regulatory T-cell immunosuppression. Additionally, the UPS intersects with key oncogenic pathways such as Wnt/β-catenin, NF-κB, and p53, further shaping the immunosuppressive landscape of CRC. CONCLUSIONS: Targeting the UPS represents a promising strategy to reverse immunosuppression and overcome therapy resistance in CRC. The primary advantage of this approach lies in its ability to simultaneously disrupt multiple immunosuppressive pathways within the TME, offering a potential solution to the limitations of single-target therapies. Current approaches include proteasome inhibitors, E3 ligase modulators, and deubiquitinating enzyme inhibitors, with combination regimens-such as UPS inhibitors with immune checkpoint blockade-showing synergistic efficacy in preclinical models. Future efforts should focus on enhancing the selectivity of UPS-targeting agents, minimizing off-target effects, and integrating genomic profiling to guide personalized treatment. While current evidence strongly supports the therapeutic potential of UPS targeting, its establishment as a reliable alternative therapy in the clinic will depend on overcoming these challenges and validating efficacy in human trials. This review underscores the UPS as a central regulator of the CRC TME and provides a rational basis for novel therapeutic development.

Humans↗
PubMed2004

Clinical nature and prognosis of locally recurrent rectal cancer after total mesorectal excision with or without preoperative radiotherapy.

PURPOSE: To document the clinical nature and prognosis of locally recurrent rectal cancer after total mesorectal excision (TME) with or without 5 x 5 Gy preoperative radiotherapy (PRT) and to identify patient-, disease-, and treatment-related factors associated with differences in prognosis after local recurrence. PATIENTS AND METHODS: For 96 Dutch patients with a local recurrence who participated in a multicenter randomized clinical trial, data on treatments and follow-up were gathered from surgeons and radiation and medical oncologists. Twenty-three patients (24%) had previously been treated with PRT plus TME, and 73 patients (76%) had been treated with TME alone. Eighty-one patients (84%) were followed until death; median follow-up time of the alive patients after local recurrence was 21 months (range, 5 to 48 months). RESULTS: Survival after local recurrence in the PRT + TME group was significantly shorter than in the TME group (median survival, 6.1 v 15.9 months; hazard ratio for death, 2.1; P =.008). Patients with a local recurrence in the PRT + TME group had distant metastases more often (74% v 40%; P =.004), underwent surgical resection of local recurrence less often (17% v 35%; P =.11), and received radiotherapy for local recurrence at a total dose >/= 45 Gy less often (4% v 42%; P =.001) than patients without PRT. In a multivariate analysis, the difference in survival after local recurrence between randomization groups was no longer statistically significant (hazard ratio for death of PRT, 1.53; P =.16). CONCLUSION: The clinical nature and prognosis of patients with locally recurrent rectal cancer has changed since the introduction of PRT. The majority of patients who present with a local recurrence after previous PRT have simultaneous distant metastases, and median survival has decreased to 6 months.

Colectomy↗
PubMed1997

Studies on Alismatis rhizoma. I. Anti-allergic effects of methanol extract and six terpene components from Alismatis rhizoma (dried rhizome of Alisma orientale).

Methanol and aqueous extracts (TMe-ext and TAq-ext) from dried rhizomes of Alisma orientale have been screened for activity in experimental models of type I-IV allergies. In the type III allergic model, TMe-ext at oral doses of 50, 200 mg/kg showed an inhibitory effect on the direct passive Arthus reaction (DPAR) in rats, while TAq-ext did not. Four triterpenes (alisol A, alisol B, alisol A monoacetate and alisol B monoacetate) and two sesquiterpenes (alismol and alismoxide) isolated from TMe-ext also exhibited this inhibitory effect. In a type I allergic model, TMe-ext inhibited 48-h homologous passive cutaneous anaphylaxis (PCA) in rats. In a type II allergic model, it was found that TMe-ext inhibits reversed cutaneous anaphylaxis (RCA) in rats. Furthermore, in a type IV allergic model, TMe-ext had an inhibitory effect on the induction phase in picryl chloride-induced contact dermatitis (PC-CD) in mice. These results indicate that Alismatis Rhizoma not only inhibits antibody-mediated allergic reactions but also influences cell reactions and should be recognized as a material for the treatment of allergic reactions, and the anti-type III allergic components are partially attributable to the terpenes mentioned above.

Animals↗
PubMed1981

An evaluation of the nitrogen correction in the true metabolizable energy assay.

This paper examined the effect of N-correction on the true metabolizable energy (TME) values of mixed diets and single ingredients using mature White Leghorn roosters. The N-corrected TME (TMEn) values were consistently higher than the corresponding TME values, the results being significant (P less than .05) in about one-half of the samples tested. This indicated a net loss in body N in the birds during the experiments. The correlations between N input and N correction were highly (P less than .01) significant. This, however, explained only 46 to 48% of the variation in the TMEn data as being due to differences in the amount of N input. In view of the present results and the abnormal condition (fasted birds) in the TME assay, it is doubtful that birds would retain enough N from a single feeding to revert to a positive body N equilibrium. Therefore, positive N retention in such an assay would be indicative of incomplete feed passage through the birds. This appears to be the only valid reason for applying N correction to TME values. However, the variations associated with N correction of TME data raise some doubt concerning the validity of this assay as compared with the conventional apparent metabolizable energy assay.

Animal Feed↗
PubMed2006

[Total mesorectal excision and preservation of autonomic nerves].

The procedure of total mesorectal excision (TME) becomes a gold standard for the treatment of rectal cancer. The reason is the marvelously low incidence of local recurrence after TME even without other adjuvant treatment, which has been reported by several independent groups. Although controversy still exists about the role of TME in upper rectal cancer, it is now widely accepted for cancers of the middle and lower third. There are number of histopathological evidences that cancer cells can spread distally several centimeters from the lower margin of cancer, and cancer bearing lymph nodes are found in the distal portion of the mesorectal tissues far from the cancer. Therefore, the distal clearance of mesorectum should be performed downwardly to the level of pelvic diaphragm (puborectalis) and the rectum is divided within a few centimeters from the pelvic floor musculature. TME defines an en-bloc procedure, along the plane between parietal and visceral pelvic fasciae. If the dissection plane is breached, the chance of visceral pelvic fascia tearing is raised and mesorectal tissue might reside in the pelvis. There are problems in auditing the procedure. As many surgeons agree, this procedure requires a learning curve. Theoretically, the autonomic nerves run between the visceral and parietal pelvic fasciae since the nerves must be preserved to make visceral fascial envelop. Any patient who become incontinent or impotent after the surgery should have received decorticating surgery other than TME. Thus, the high quality of TME should fulfill two clinical measurements: absence of impotence or incontinence and at least single digit, 5-year, cumulative recurrence rate regardless of adjuvant therapy.

Autonomic Pathways↗
PubMed1997

Anatomical basis and rationale of total mesorectal excision.

The concept of TME for cancer of the mid rectum has been introduced by Heald in 1982. Since then the evidence in favor of routinely applying TME in all operable cases of mid and low rectal cancer has kept growing. TME has been shown to reduce the number of R1 resections and increase the number of R0 resections, resulting in a significantly reduced recurrence rate compared to traditional surgical technique. The authors have produced a video which illustrates the anatomical basis and technical details of TME. TME is the resection of the rectum together with the fatty and lymphatic tissue contained within the visceral sheet of the pelvic fascia. This paper details the anatomical basis of TME, describing the fascial structures and fibrous spaces along which the dissection must proceed.

Adipose Tissue↗
PubMed2000

Total mesorectal excision for surgical treatment of rectal cancer.

BACKGROUND AND OBJECTIVES: The aim of our study was to retrospectively evaluate the results of 2 groups of patients admitted and treated for rectal cancer. METHODS: One hundred and fifty-one patients were available for evaluation. Eighty (group A) were radically operated with the standard technique; 71 (group B) underwent total mesorectal excision (TME). Groups were similar according to demographics, staging, and pathological data. Mean follow-up was 73.5 months. RESULTS: No operative mortality was observed. Complications were 15% in group A and 32% in group B. Local recurrence rates were 41.2% in group A and 12.6% in group B. Distant metastases occurred in 21.2% and 7.6%, respectively, in groups A and B. Cancer-related mortality was 62.5% in the non-TME group and 19.5% in the TME group. Overall 5-year survival rates were 32.4% in group A and 70.5% in group B. Disease-free survival rates were 25% in group A and 62.3% in group B. CONCLUSIONS: TME appears to lower the incidence of cancer-related mortality, with a higher incidence of postoperative complications. Further studies need to be done to assess the real benefits of TME in the surgical treatment of rectal cancer.

Female↗
PubMed2005

Impact of a surgical training programme on rectal cancer outcomes in Stockholm.

BACKGROUND: Total mesorectal excision (TME) and use of adjuvant radiotherapy are major advances in the treatment of rectal cancer that have emerged in the past 20 years. The aim of this study was to evaluate the effects of an initiative to teach the TME technique on outcomes at 5 years after surgery. METHODS: TME-based surgery was introduced in Stockholm in 1994. The study population comprised all 447 patients who underwent abdominal operations for rectal cancer in Stockholm County during 1995 and 1996. Outcomes were compared with those in the Stockholm I (790 patients) and Stockholm II (542 patients) radiotherapy trials. RESULTS: The permanent stoma rate was reduced from 60.3 and 55.3 per cent in the Stockholm I and II trials respectively to 26.5 per cent in the TME project (P < 0.001). Five-year local recurrence rates decreased from 21.9 and 19.1 per cent to 8.2 per cent respectively (P < 0.001). Five-year cancer-specific survival rates increased from 66.0 and 65.7 per cent in the Stockholm trials to 77.3 per cent in the TME project (hazard ratio 0.62 (95 per cent confidence interval 0.49 to 0.80); P < 0.001). CONCLUSION: A surgical teaching programme had a major impact on rectal cancer outcome.

Adult↗
PubMed2004

Total mesorectal excision for middle and lower rectal cancer: a single institution experience with 337 consecutive patients.

BACKGROUND AND OBJECTIVES: There have been reports on improved prognosis after TME for middle and lower rectal cancer. No prospective randomized studies have yet been performed. This is a large single institution series evaluating its own results of TME. METHODS: This retrospective study analyses data of 337 patients with middle and lower rectal cancer, treated with either curative or palliative intention between 1990 and 1998. RESULTS: Of all patients, 212 had lower rectal and 125 middle rectal carcinomas. The rate of rectal resections with TME was 96%. A total of 223 patients were treated by anterior rectal resection; 92 patients had to undergo abdomino-perineal resection. Ten patients were operated by a Hartmann resection. Postoperative morbidity was 35% with a leakage rate of 9%. Postoperative mortality was 4%. The rate of local recurrence was 8.6%. The 5-year survival rate after curative resection was 69.3%. The multivariate analysis outlined the tumor stage as independent prognostic factor. CONCLUSIONS: In our experience, TME is feasible with acceptable postoperative morbidity and low mortality. The local recurrence rate can be decreased to lower than 10%. The almost 70% 5-year survival rate indicates a clear benefit for the patients. These findings recommend TME as standard procedure for middle and lower rectal cancer.

Adult↗
PubMed1981

[Plasma catecholamines, metabolic substrates, aerobic and anaerobic capacity during graduated treadmill and bicycle ergometer exercise (author's transl)].

Adrenaline, noradrenaline, glucose, lactate, free fatty acids, and glycerine in blood, as well as heart frequency and oxygen intake were examined in 6 healthy male subjects (28 +/- 2.6 years) before, during and after a graduated treadmill (TME) and bicycle ergometer (BE) test. Adrenaline, noradrenaline, the energy supplying substrates, and the oxygen-intake show no differences during TME and BE at given submaximal levels. Noradrenaline is 27% (0.10 less than p less than 0.05) higher, pulse rate is 6% (p less than 0.05) lower, oxygen intake 4% (greater than 0.05) lower, and the glycerine level 25% (0.10 less than p less than 0.05) lower during maximal BE exercise. The tendency toward a higher noradrenaline release during BE exercise can be influenced by a greater static-pressure stress opposed to a dynamic-circulatory stress during TME testing. An increased alphareceptor stimulation leads to a negative chronotropic effect, whose cause is assumed to be a baroreceptor stimulation. The TME induces a higher circulation and a more economic oxygen supplying of the muscles exercised, as well as a favourable fat oxidation, which is recognizable by a more rapid increase of glycerine (0.10 less than p less than 0.05). When referring to exercise acidification (a tendency toward a lower lactate production during submaximal TME testing shows here), oxygen intake capability, energy supplying substrates, and the catecholamines, both forms of ergometer testing are comparable one to another; a falsification appears only when plasma catecholamines and lactate levels are based on the heart frequency, as it is influenced by the form of exercise.

Adult↗
PubMed2005

Laparoscopic rectal resection with anal sphincter preservation for rectal cancer: long-term outcome.

BACKGROUND: Total mesorectal excision (TME) is the surgical gold standard treatment for middle and low third rectal carcinoma. Laparoscopy has gradually become accepted for the treatment of colorectal malignancy after a long period of questions regarding its safety. The purposes of this study were to examine prospectively our experience with laparoscopic TME and high rectal resections, to evaluate the surgical outcomes and oncologic adequacy, and to discuss the role of this procedure in the treatment of rectal cancer. METHODS: Between December 1992 and December 2004, all patients who underwent elective laparoscopic sphincter preserving rectal resection for rectal cancer were enrolled prospectively in this study. Data collection included preoperative, operative, postoperative and oncologic results with long-term follow-up. RESULTS: A total of 218 patients were operated on during the study period: 142 patients underwent laparoscopic TME and 76 patients underwent anterior resection. Of the TME patients, 122 patients were operated using the double-stapling technique, and 20 patients underwent colo-anal anastomosis with hand-sewn sutures. Mean operative time was 138 min (range, 107-205), and mean blood loss was 120 ml (range, 30-350). Conversion to open surgery occurred in 26 cases (12%). Mortality rate during the first 30 days was 1%. Anastomotic leaks were observed in 10.5% of the patients. Of these, 61.9% needed reoperation and diverting stoma, and the rest were treated conservatively. Three patients had postoperative bleeding requiring relaparoscopy. Other minor complications (infection and urinary retention) occurred in 9.1% of patients. Mean ambulation time and mean hospital stay were 1.6 days (range, 1-5) and 6.4 days (range, 3-28) , respectively. Patients were followed for a mean period of 57 months. No port site metastases were observed during follow-up. The recurrence rate was 6.8 %. Overall survival rate was 67% after 5 years and 53.5% after 10 years. CONCLUSION: Laparoscopic anterior resection and TME with anal sphincter preservation for rectal cancer is feasible and safe. The short- and long-term outcomes reported in this series are comparable with those of conventional surgery.

Adult↗
PubMed2004

Locally recurrent rectal cancer after curative resection.

BACKGROUND: To determine the incidence of local recurrence, after curative resection for rectal cancer, with the application of total mesorectal excision (TME). PATIENTS AND METHODS: During the last ten years, 120 patients underwent curative resection for rectal cancer. As a rule, except for the cases that underwent high anterior resection, TME was applied. In terms of local relapse, routine TME, preoperative radiotherapy, tumour's stage, differentiation grade and number of positive nodes were taken into account. RESULTS: Eight patients (6.7%) presented with local relapse. At 5 years, 91.9% of patients were free of local recurrence and the actuarial disease-free survival was 81%. A significant association between routine TME, tumour's stage, differentiation grade, lymph node invasion and local recurrence was observed. Conversely, preoperative radiotherapy appeared to play no protective role. CONCLUSIONS: The curative resection of rectal cancer, with the application of TME, has led to a very low incidence of local relapse during the last few years.

Adult↗
PubMed1991

Dissection of murine lymphocyte-endothelial cell interaction mechanisms by SV-40-transformed mouse endothelial cell lines: novel mechanisms mediating basal binding, and alpha 4-integrin-dependent cytokine-induced adhesion.

Lymph node-derived endothelial cells were immortalized by infection with SV40 virus and subclones expressing the marker MECA 325 specific for high-endothelial venules (HEV) were selected. These transformed mouse endothelial (TME-) cell lines grow permanently without requirement for special growth factors. Staining of the selected clones with endothelium-specific antibodies and with anti-von Willebrand factor antiserum and uptake of acetylated low-density lipoprotein provide evidence for their endothelial origin. The vascular addressins identified by mAbs MECA 79 and MECA 367 on HEV are not detectable, indicating that the phenotype of the cells differs from that of HEV-type endothelium. The TME cells display a constitutive capacity to bind lymphocytes. An additional binding component is induced by treatment of the TME cells with TNF alpha. Antibodies against the homing receptor LECAM-1 (lectin-related leucocyte-endothelial cell adhesion molecule 1), alpha 4-integrins, vascular addressins, LFA-1, or ICAM-1 known to block lymphocyte interaction with particular types of HEV were unable to inhibit the basal adhesion to TME cells, indicating that a further binding mechanism in mice is displayed by this cell type. The adhesion component induced by TNF alpha is mediated by alpha 4-integrins since enhanced binding could be blocked by an antibody against mouse alpha 4 (lymphocyte-Peyer's patch adhesion molecule 1/2). TME cell lines therefore seem to be a useful model for the dissection and analysis of hitherto poorly characterized murine lymphocyte/endothelial cell interaction mechanisms.

Animals↗
PubMed1994

Recombinant soluble human thrombomodulin: a randomized, blinded assessment of prevention of venous thrombosis and effects on hemostatic parameters in a rat model.

UNLABELLED: Thrombomodulin is an endothelial surface receptor that binds thrombin and accelerates the activation of protein C. We compared the effects of a recombinant thrombomodulin analog (TME), recombinant hirudin (r-HIR), heparin sodium (HEP), and normal saline (Control) on thrombus formation, activated partial thromboplastin time (APTT), thrombin time (TT), platelet aggregation and tail transection bleeding time (BT) in a rat model of vena cava thrombosis. RESULTS: TME, r-HIR and HEP prevented venous thrombosis in this model in a dose-dependent manner. At the dose required to reduce vena cava thrombosis by 50% (ED50), TME did not prolong the APTT or TT as did HEP and r-HIR. Platelet aggregation in response to thrombin was not effected by TME but was inhibited by both r-HIR and HEP. BT did not differentiate the agents tested. CONCLUSION: TME inhibited venous thrombosis in a rat vena cava model with less effect on hemostatic variables than HEP or r-HIR.

Animals↗
PubMed2006

Efforts to improve local control in rectal cancer compromise survival by the potential morbidity of optimal mesorectal excision.

BACKGROUND: The technique of total mesorectal excision (TME) increases the risk of anastomotic leakage. The impact of postoperative morbidity of TME on longterm survival has never been described. We retrospectively analyzed factors that might influence survival after TME for rectal cancer, including postoperative morbidity. STUDY DESIGN: From 1994 to 2001, 300 patients (192 men and 108 women; mean age, 64 years) had TME for rectal cancer. Preoperative radiotherapy was given in 202 patients. Age, gender, tumor height, size and circular invasion of the tumor, pathologic tumor and nodal status, distal and circumferential margins, number of lymph nodes analyzed, type of surgery, postoperative pelvic sepsis, preoperative radiotherapy, and adjuvant chemotherapy were examined; their association with overall and disease-free survival was evaluated by the log-rank test in univariate analysis and by multivariable Cox proportional hazards analysis. RESULTS: Postoperative morbidity was 38% (113 of 300 patients) and included 18% (54 of 300 patients) pelvic sepsis. The local recurrence rate was 6% (18 of 300 patients), and the distant metastasis rate was 24% (73 of 300 patients). Recurrence was three times more frequent distally than locally, including patients with pelvic sepsis The 5-year overall and disease-free survival rates were 72% and 60%, respectively. Independent predictors of overall survival were age older than 64 years (odds ration [OR]=2.19, 95% CI 1.32 to 4.17), pelvic sepsis (OR=2.06, 95% CI 1.10 to 3.87), circumferential surgical margin (OR=3.19, 95% CI 1.67 to 6.09), pathologic tumor (OR=2.69, 95% CI1.23 to 5.88), and nodal status (OR=3.18, 95% CI 1.79 to 5.64). Independent predictors of disease-free survival were pelvic sepsis (OR=2.17, 95% CI 1.31 to 3.58), circumferential surgical margin (OR=2.61, 95 CI 1.52 to 4.49), pathologic tumor (OR=1.82, 95% CI 1.04 to 3.20), and nodal status (OR=2.67, 95% CI 1.68 to 4.23). Patients with pelvic sepsis had a 5-year disease-free survival of 39% compared with 65% without pelvic sepsis (p<0.001). CONCLUSIONS: After TME for rectal cancer, pelvic sepsis is a common complication that is associated with increased risk of distant recurrence and decreased longterm survival. Efforts are necessary to decrease postoperative morbidity in surgical treatment of rectal cancer.

Adenocarcinoma↗