Postoperative three-dimensional endoanal ultrasound findings and relation to anal fistula plug failure.

OBJECTIVES: To explore the utilization of three-dimensional (3D) endoanal ultrasound (EAUS) for the follow-up of the anal fistula plug (AFP), describe morphological findings in postoperative 3D EAUS, and evaluate if postoperative 3D EAUS combined with clinical symptoms can predict AFP failure. MATERIALS AND METHODS: A retrospective analysis of 3D EAUS examinations performed during a single-centre study of prospectively included consecutive patients treated with the AFP between May 2006 and October 2009. Postoperative assessment by clinical examination and 3D EAUS was performed at 2 weeks, 3 months and 6-12 months ("late control"). Long-term follow-up was carried out in 2017. The 3D EAUS examinations were blinded and analysed by two observers using a protocol with defined relevant findings for different follow-up time points. RESULTS: A total of 95 patients with a total of 151 AFP procedures were included. Long-term follow-up was completed in 90 (95%) patients. Inflammation at 3 months, gas in fistula and visible fistula at 3 months and at late control, were statistically significant 3D EAUS findings for AFP failure. The combination of gas in fistula and clinical finding of fluid discharge through the external fistula opening 3 months postoperatively was statistically significant (p < 0.001) for AFP failure with 91% sensitivity and 79% specificity. The positive predictive value was 91%, while the negative predictive value was 79%. CONCLUSIONS: 3D EAUS may be utilized for the follow-up of AFP treatment. Postoperative 3D EAUS at 3 months or later, especially if combined with clinical symptoms, can be used to predict long-term AFP failure.ClinicalTrials.gov identifier NCT03961984.

Administration of probiotics to healthy volunteers: effects on reactivity of intestinal mucosa and systemic leukocytes.

BACKGROUND: Oral administration of health-promoting bacteria is increasingly used in clinical practise. These bacteria have anti-inflammatory characteristics and modulate the immune system without major reported side effects. The mechanisms of action are not yet fully defined. Our aim was to study systemic effects of probiotics by measurements of leukocytes as well as local effects on rectal mucosal biopsies after adding a standardized inflammatory stimulus in vitro. METHODS: Fourteen healthy subjects were randomized to receive 1010 colony forming units/day orally of the probiotic strain Lactiplantibacillus plantarum 299 (Lp299), n = 7, or Bifidobacterium infantis CURE21 (CURE21), n = 7, for six weeks. Rectal biopsies were taken before and after ingestion of either probiotic strain product, for stimulation in vitro with tumour necrosis factor alpha (TNF-α) at 10 and 100 ng/ml respectively up to 8 h. Blood tests were sampled before and after treatment. Lactate dehydrogenase (LDH) confirmed viable tissue. RESULTS: Composition of the intestinal microbiota was not changed. Systemic leukocytes decreased after administration of CURE21 (P<0.05) and Lp299 (P<0.01). Levels of the pro-inflammatory cytokine IL-6 in rectal mucosa after stimulation with TNF-α were attenuated after ingestion of Lp299. No effect was seen with CURE21. CONCLUSIONS: Administration of these probiotic strains to healthy humans show both a systemic and local reduction of inflammatory response by lowering leukocyte counts, and for Lp299 IL-6 levels in rectal mucosa. Probiotics may play an important role in the reduction of inflammatory responses expected after trauma during surgery or after pelvic irradiation. Trial registration Clinical Trials, registration number NCT01534572, retrospectively registered ( http://www.clinicaltrials.gov ).

The Comparative Effects of Mesenchymal Stem Cell Transplantation Therapy for Spinal Cord Injury in Humans and Animal Models: A Systematic Review and Meta-Analysis.

Animal models have been used in preclinical research to examine potential new treatments for spinal cord injury (SCI), including mesenchymal stem cell (MSC) transplantation. MSC transplants have been studied in early human trials. Whether the animal models represent the human studies is unclear. This systematic review and meta-analysis has examined the effects of MSC transplants in human and animal studies. Following searches of PubMed, Clinical Trials and the Cochrane Library, published papers were screened, and data were extracted and analysed. MSC transplantation was associated with significantly improved motor and sensory function in humans, and significantly increased locomotor function in animals. However, there are discrepancies between the studies of human participants and animal models, including timing of MSC transplant post-injury and source of MSCs. Additionally, difficulty in the comparison of functional outcome measures across species limits the predictive nature of the animal research. These findings have been summarised, and recommendations for further research are discussed to better enable the translation of animal models to MSC-based human clinical therapy.

Long-term outcome of the Surgisis® (Biodesign® ) anal fistula plug for complex cryptoglandular and Crohn's fistulas.

AIM: To evaluate the long-term success rate of treatment with the Surgisis® (Biodesign® ) anal fistula plug for complex anal fistulas, assess fistula plug failure over time and compare success rates for fistula plug between a group of patients with cryptoglandular fistula and another group with Crohn's fistula. METHOD: This is a single-centre study of consecutive patients treated with the Surgisis® (Biodesign® ) anal fistula plug between May 2006 and October 2009. All patients had complex anal fistulas in need of surgical treatment. The patients were assessed preoperatively by physical examination and three-dimensional (3D) endoanal ultrasound, and treated with a loose seton. Postoperative assessment by clinical examination and 3D endoanal ultrasound was performed at 2 weeks, 3 months and 6-12 months. Long-term follow-up was carried out in 2017 using a questionnaire, and clinical examination combined with 3D endoanal ultrasound was performed if the questionnaire indicated any signs of fistula recurrence. RESULTS: A total of 95 patients were included; 30 had quiescent Crohn's disease. Overall, 151 plug procedures were performed. Long-term follow-up was undertaken in 90 (95%) patients; the results showed that after a median period of 110 months, the overall healing rate after one to five plug procedures was 38%. No statistically significant difference in success rate was found between the cryptoglandular fistula group and the Crohn's fistula group (P = 0.37). No further healing was observed after the use of three plugs. CONCLUSION: Considering its low morbidity in a complex disease with high recurrence rates over time, the anal fistula plug may still be considered as one of the first-line treatments for patients with complex anal fistulas.

An In Vitro Comparison of the Neurotrophic and Angiogenic Activity of Human and Canine Adipose-Derived Mesenchymal Stem Cells (MSCs): Translating MSC-Based Therapies for Spinal Cord Injury.

The majority of research into the effects of mesenchymal stem cell (MSC) transplants on spinal cord injury (SCI) is performed in rodent models, which may help inform on mechanisms of action, but does not represent the scale and wound heterogeneity seen in human SCI. In contrast, SCI in dogs occurs naturally, is more akin to human SCI, and can be used to help address important aspects of the development of human MSC-based therapies. To enable translation to the clinic and comparison across species, we have examined the paracrine, regenerative capacity of human and canine adipose-derived MSCs in vitro. MSCs were initially phenotyped according to tissue culture plastic adherence, cluster of differentiation (CD) immunoprofiling and tri-lineage differentiation potential. Conditioned medium (CM) from MSC cultures was then assessed for its neurotrophic and angiogenic activity using established cell-based assays. MSC CM significantly increased neuronal cell proliferation, neurite outgrowth, and ßIII tubulin immunopositivity. In addition, MSC CM significantly increased endothelial cell migration, cell proliferation and the formation of tubule-like structures in Matrigel assays. There were no marked or significant differences in the capacity of human or canine MSC CM to stimulate neuronal cell or endothelial cell activity. Hence, this study supports the use of MSC transplants for canine SCI; furthermore, it increases understanding of how this may subsequently provide useful information and translate to MSC transplants for human SCI.

Percutaneous tibial nerve stimulation (PTNS): an alternative treatment option for chronic therapy resistant anal fissure.

BACKGROUND: The aim of the present study was to evaluate percutaneous tibial nerve stimulation (PTNS) for treatment resistant chronic anal fissure. METHODS: Consecutive patients with chronic anal fissure were treated with neuromodulation via the posterior tibial nerve between October 2013 and January 2014. Patients had PTNS for 30 min on 10 consecutive days. All patients had failed conventional medical treatment. The visual analogue scale (VAS) score, St. Marks score, Wexner's constipation score, Brief Pain Inventory (BPI-SF), bleeding and mucosal healing were evaluated before treatment, at termination, after 3 months, and then yearly for 3 years. RESULTS: Ten patients (4 males and 6 females; mean age 49.8 years) were identified but only 9 were evaluated as one patient's fissure healed before PTNS was started. At 3-year follow-up, fissures had remained completely healed in 5 out of 9 patients. All patients stopped bleeding and were almost completely pain-free at 3 years (VAS p = 0.010) and pain relief improved from 50% at completion to 90% at 3 years. The patients' Wexner constipation scores improved significantly (p = 0.007). CONCLUSIONS: In this small series, PTNS enhanced healing of chronic anal fissure and reduced pain and bleeding with an associated improvement in bowel function.

MMP7 Modulation by Short- and Long-term Radiotherapy in Patients with Rectal Cancer.

BACKGROUND/AIM: Matrix metalloproteinase 7 (MMP7) expression is highly associated with colorectal cancer and modulates tumour growth and invasion. Radiation injury induces inflammation with increases in MMP7 and in transforming growth factor beta (TGFß). The aim of this study was to investigate the effect on MMP7 and TGFß. expression in patients with rectal cancer undergoing different regimens of neoadjuvant radiotherapy (RT). PATIENTS AND METHODS: We studied 53 patients in three RT treatment groups receiving RT of 25 Gy, long-term RT 50 Gy and controls receiving no RT. Three biopsies were obtained from each patient during the treatments: before RT, after RT and after surgery. Tissue samples were formalin fixed, paraffin embedded and tissue microarrays were constructed and stained for MMP7 and TGFß. Mann-Whitney U-tests and Wilcoxon Z-tests were used to determine differences between patients before and after RT, and after surgery, as well as between the RT groups. RESULTS: In all three patient groups, increases of MMP7 and TGFß expression were observed after surgery. MMP7 expression was significantly increased in patients receiving short-term RT but TGFß expression was not affected by RT. CONCLUSION: 50 Gy Irradiation of rectal cancer gives less tumour activation of MMP7, whilst it is up-regulated by 25 Gy and surgery regardless of RT.

Timing and extension of lymphadenectomy in medullary thyroid carcinoma: A case series from a single institution.

BACKGROUND: Medullary thyroid carcinoma is an aggressive tumor and presents with significant morbidity and mortality and a high rate of lymph node metastases. The combination of total thyroidectomy and cervical lymphadenectomy is the essential treatment for those patients presenting with cervical lymph node metastases. MATERIALS AND METHODS: A retrospective analysis of 117 patients operated for medullary thyroid carcinoma over a period of 15 years at a single institution. Surgical complications and calcitonin levels were noted. RESULTS: Nodal metastases were detected in the central compartment in 72.6% patients. Positive lymph nodes were detected in the lateral compartment of 34 patients who had undergone ipsilateral dissection and in all 10 patients of those with bilateral surgery. We found 3 cases of unilateral transient recurrent laryngeal nerve palsy, 15 cases of temporary hypoparathyroidism, a permanent accessory nerve lesion and a case of chylous fistula. Normalization of post-operative calcitonin was found in 82.6% and of patients who underwent total thyroidectomy and central neck dissection alone compared to 35.4% in those with ipsilateral and bilateral neck dissection. CONCLUSIONS: Total thyroidectomy and cervical lymphadenectomy planned on the ultrasound preoperative study and on the calcitonin level represent the standard of treatment for medullary thyroid carcinoma.

Current Indications for Surgical Treatment of Primary Hyperparathyroidism in the Elderly.

This study presents the results of surgery in the elderly for primary hyperparathyroidism (PHPT) from a single institution's experience. We retrospectively analyzed 898 cases of surgically treated PHPT, divided into two groups: 135 elderly patients (A) and 763 patients younger than 65 years (B). PHPT was symptomatic in 68.8 per cent patients in group A and in 81.6 per cent in group B. Unilateral temporary recurrent laryngeal nerve palsy was observed in 0.9 per cent in group A and 0.1 per cent in group B (P > 0.05). No cervical hematomas, mortality or major cardiovascular, neurological, respiratory or metabolic postoperative complications were registered. All the patients evaluated at one year had improvement in the quality of life, with increase of bone mineral density (BMD) in 85.6 per cent and 79.8 per cent of patients in groups A and B, with no significant differences between symptomatic and asymptomatic patients. Parathyroidectomy in elderly PHPT patients is safe, with rate of morbidity similar to what observed in younger individuals. Further investigations are recommended to confirm the role of surgery as an effective approach in elderly PHPT patients.

Laparoscopic hepatectomy for HCC in elderly patients: risks and feasibility.

BACKGROUND: Laparoscopic liver resection (LLR) appears to be safe and effective as open liver resection (OLR) for hepatocellular carcinoma (HCC). However, studies comparing LLR with ORL in elderly patients are limited. The purpose of this study is to compare the clinical outcomes of LLR versus OLR for HCC in elderly patients. METHODS: A retrospective analysis was made comparing laparoscopic (n = 11) and open (n = 18) liver resections in elderly patients performed at the University of Naples "Federico II" between January 2010 and December 2014. Demographic data, operative and postoperative outcomes were analyzed. RESULTS: Demographic and tumor characteristics of laparoscopic and OLRs were similar. There were also no significant differences in operating room time. Patients undergoing OLR had increased rate of minor complications (33 vs. 0%), longer lengths of stay (6 vs. 3 days) and higher blood loss (310 ± 84 vs. 198 ± 34 ml). There were no significant differences in major complication rates or 90-day mortality. DISCUSSION: LLR is safe and feasible as OLR for treatment of HCC in selected elderly patients.

Surgical treatment of secondary hyperparathyroidism in elderly patients: an institutional experience.

BACKGROUND: Secondary hyperparathyroidism in elderly fragile patients presents clinical difficulties due to severity of symptoms and related comorbidity. The optimal surgical approach for this group of patients is still debated. AIM: The aim of the study was to define the optimal technique of parathyroidectomy in elderly patients with secondary hyperparathyroidism. METHODS: Retrospective analysis in a series of 253 patients including 35 elderly individuals at a single institution was carried out. Postoperative parathyroid hormone decrease, surgical complications and symptoms control were analyzed for all patients in relation to the types of parathyroidectomy performed. RESULTS: In elderly patients, total parathyroidectomy was the most used approach. Subtotal parathyroidectomy was mostly reserved for younger patients suitable for kidney transplantation. No elderly patients treated with total parathyroidectomy were autotransplanted. No significant difference in surgical complications was observed between younger and elderly patients and considering the different procedures. Adequate symptom control after surgery was achieved in almost 90% of patients. A limited rate of recurrence requiring repeat surgery was observed only after subtotal parathyroidectomy. DISCUSSION: Considering the features of all types of parathyroidectomy, very low recurrence rate, contained postoperative hypocalcemia and limited complications following total parathyroidectomy, might represent specific advantages for elderly patients. CONCLUSIONS: Total parathyroidectomy without parathyroid transplantation is safe for elderly patients with secondary hyperparathyroidism and a good alternative to the well-established total parathyroidectomy with autografting.

Laparoscopic distal pancreatectomy in elderly patients: is it safe?

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) appears to be safe and effective as open distal pancreatectomy (ODP) for benign or borderline malignant lesion. However, studies comparing LDP with ODP in elderly patients are limited. The purpose of this study is to compare the clinical outcomes of these two several approaches in elderly patients. METHODS: A retrospective analysis was carried out by comparing laparoscopic (n = 7) and open (n = 15) distal pancreatectomy in elderly patients performed at the University of Naples "Federico II" and University of Perugia between January 2012 and December 2015. Demographic data, operative and postoperative outcomes were analyzed. RESULTS: Demographic and tumor characteristics of laparoscopic and ODP were similar. There were also no significant differences in operating room time. Patients undergoing LDP had lower blood loss, first flatus time, diet start time and postoperative hospital stay. There were no significant differences in complication rates or 90-day mortality. DISCUSSION: LDP is safe and feasible as ODP in selected elderly patients.

An open prospective study evaluating efficacy and safety of a new medical device for rectal application of activated carbon in the treatment of chronic, uncomplicated perianal fistulas.

PURPOSE: It has been proposed that biological/chemical substances in the intestine might play a role in the occurrence and deterioration of perianal fistulas. Elimination of such unidentified factors from the lower gastrointestinal tract might offer a new strategy for the management of anal fistulas. The aim of this study was to evaluate the clinical effects on non-Crohn's disease perianal fistula healing, and the safety and tolerability of a new medical device that applies high-purity, high-activity granular activated carbon locally into the rectum twice daily of patients with perianal fistulas without any concomitant medication. METHODS: An open, single-arm, prospective study with active treatment for 8 weeks and an optional follow-up until week 24 ( ClinicalTrial.gov identifier NCT01462747) among patients with chronic, uncomplicated perianal fistulas scheduled for surgery was conducted. RESULTS: Of 28 patients included, 10 patients (35.7%) showed complete fistula healing (closed, no discharge on palpation) after 8 weeks; seven of these patients, corresponding to 25% of the enrolled patients, remained in remission for up to 31 weeks. At week 8, there was a statistically significant reduction in the discharge visual analog scale (p = 0.04), a significant improvement in the patient-perceived quality of life for the category of embarrassment (p = 0.002), and a trend toward improvement in the other assessment categories. CONCLUSIONS: The treatment was well tolerated, and patient acceptance was high. The results support the efficacy and safety of locally administered activated carbon for the treatment of patients with chronic uncomplicated perianal fistulas not receiving any other medication for fistula problems.

Factorial Design of Experiments to Optimize Multiple Protein Delivery for Cardiac Repair.

Myocardial infarction (MI) is a major cardiovascular disease responsible for millions of deaths annually. Protein therapies can potentially repair and regenerate the infarcted myocardium. However, because of the short half-lives of proteins in vivo, their low retention at the target tissue, and the lack of spatiotemporal cues upon injection, the efficacy of protein therapy can be limited. This efficacy can be improved by utilizing controlled release systems to overcome shortcomings associated with a direct bolus injection. Equally important is the determination of an optimal combination of different proteins having distinct roles in cardiac function and repairs to prevent or reverse the multiple pathologies that develop after infarction. In this work, we used a rat MI model to test a combination of potentially complementary proteins: tissue inhibitor of metalloproteinases 3 (TIMP-3), interleukin-10 (IL-10), basic fibroblast growth factor (FGF-2), and stromal cell-derived factor 1 alpha (SDF-1α). To achieve controlled and timed release of the proteins per their physiologic cues during proper tissue repair, we used a fibrin gel-coacervate composite. TIMP-3 and IL-10 were encapsulated in fibrin gel to offer early release, while FGF-2 and SDF-1α were encapsulated in heparin-based coacervates and distributed in the same fibrin gel to offer sustained release. We utilized a powerful statistical tool, factorial design of experiments (DOE), to refine this protein combination based on its improvement of ejection fraction 4 weeks after MI. We found that TIMP-3, FGF-2, and SDF-1α demonstrated significant contributions toward improving the ejection fraction, while the IL-10's effect was insignificant. The results also suggested that the higher doses tested for TIMP-3, FGF-2, and SDF-1α had greater benefit on function than lower doses and that there existed slight antagonism between TIMP-3 and FGF-2. Taken together, we conclude that factorial DOE can guide the evolution of multiple protein therapies in a small number of runs, saving time, money, and resources for finding the optimal dose and composition.

MMP7 expression in colorectal tumours of different stages.

BACKGROUND/AIM: Matrix metalloproteinases (MMPs) are involved in cancer biology. Expression of MMP7 (matrilysin) in colorectal cancer is associated with metastatic disease even though it is expressed in most tumour states. In the present study, our purpose was to analyze MMP7 in bowel and lymph nodes of different tumour stages and to evaluate its expression as a cancer biomarker. PATIENTS AND METHODS: 28 patients surgically-treated for benign and malignant colorectal tumours were recruited and analyzed for MMP7 in tumoural tissue, lymph nodes and serum by histology, immunohistochemistry, ELISA and western blotting. RESULTS: Immunohistochemistry showed prevalent expression of MMP7 in advanced cancer. A significant increase (p<0.001) was evident in serum of stage III/IV cancers compared to both adenomas and non-metastatic disease. MMP7 was increased in cancer tissues with prevalence in stage I/II. Lymph nodes presented a significant increase of MMP7 (p<0.05 adenoma vs. stage I/II and p<0.001 vs. stage III/IV). CONCLUSION: MMP7 increases with dysplasia and cancer disease stage in tumour tissue as well as in the regional lymph nodes. It may be used as a complement in investigating suspected locally advanced cancer.

High nuclear RBM3 expression is associated with an improved prognosis in colorectal cancer.

PURPOSE: In this study, we investigated the prognostic impact of human RBM3 expression in colorectal cancer using tissue microarray-based immunohistochemical analysis. EXPERIMENTAL DESIGN: One polyclonal antibody and four monoclonal anti-RBM3 antibodies were generated and epitope mapped using two different methods. Bacterial display revealed five distinct epitopes for the polyclonal antibody, while the four mouse monoclonal antibodies were found to bind to three of the five epitopes. A peptide suspension bead array assay confirmed the five epitopes of the polyclonal antibody, while only one of the monoclonal antibodies could be mapped using this approach. Antibody specificity was confirmed by Western blotting and immunohistochemistry, including siRNA-mediated knock-down. Two of the antibodies (polyclonal and monoclonal) were subsequently used to analyze RBM3 expression in tumor samples from two independent colorectal cancer cohorts, one consecutive cohort (n=270) and one prospectively collected cohort of patients with cancer of the sigmoid colon (n=305). RBM3-expression was detected, with high correlation between both antibodies (R=0.81, p<0.001). RESULTS: In both cohorts, tumors with high nuclear RBM3 staining had significantly prolonged the overall survival. This was also confirmed in multivariate analysis, adjusted for established prognostic factors. CONCLUSION AND CLINICAL RELEVANCE: These data demonstrate that high tumor-specific nuclear expression of RBM3 is an independent predictor of good prognosis in colorectal cancer.

Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients.

BACKGROUND: We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI) in both tumour tissue (t-TATI) and in serum (s-TATI) are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT) on concentrations of t-TATI and s-TATI in patients with rectal cancer. METHODS: TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 × 5 Gy (short-term) preoperative RT and 21 patients 25 × 2 Gy (long-term) preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z) test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R) test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS) according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test. RESULTS: RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P < 0.001). T-TATI expression correlated with male gender (R = 0.406, P = 0.008). High t-TATI expression in surgical specimens was associated with a significantly shorter OS (P = 0.045). S-TATI concentrations in serum drawn at all time points were associated with an impaired OS (P = 0.035 before RT, P = 0.001 prior to surgery, P = 0.043 post surgery). At all time points, s-TATI correlated with higher age (P < 0.001-0.021) and with increased s-creatinine concentrations assessed prior to surgery (P = 0.041). CONCLUSIONS: The results presented here further validate the utility of t-TATI and s-TATI as prognostic biomarkers in patients with rectal cancer, independent of neoadjuvant RT.

SATB2 in combination with cytokeratin 20 identifies over 95% of all colorectal carcinomas.

The special AT-rich sequence-binding protein 2 (SATB2), a nuclear matrix-associated transcription factor and epigenetic regulator, was identified as a tissue type-specific protein when screening protein expression patterns in human normal and cancer tissues using an antibody-based proteomics approach. In this respect, the SATB2 protein shows a selective pattern of expression and, within cells of epithelial lineages, SATB2 expression is restricted to glandular cells lining the lower gastrointestinal tract. The expression of SATB2 protein is primarily preserved in cancer cells of colorectal origin, indicating that SATB2 could function as a clinically useful diagnostic marker to distinguish colorectal cancer (CRC) from other types of cancer. The aim of this study was to further explore and validate the specific expression pattern of SATB2 as a clinical biomarker and to compare SATB2 with the well-known cytokeratin 20 (CK20). Immunohistochemistry was used to analyze the extent of SATB2 expression in tissue microarrays with tumors from 9 independent cohorts of patients with primary and metastatic CRCs (n=1882). Our results show that SATB2 is a sensitive and highly specific marker for CRC with distinct positivity in 85% of all CRCs, and that SATB2 and/or CK20 was positive in 97% of CRCs. In conclusion, the specific expression of SATB2 in a large majority of CRCs suggests that SATB2 can be used as an important complementary tool for the differential diagnosis of carcinoma of unknown primary origin.

Matrilysin expression related to radiation and microflora changes in murine bowel.

BACKGROUND: Matrilysin (MMP-7) elevation after radiotherapy is shown in humans. Matrilysin regulates certain cytokines and the production of bactericidal proteins when the mucosa is exposed to bacterial antigens. We investigate the effect of irradiation on matrilysin and microflora in murine bowel, after modulation with antibiotics. METHODS: Animals were divided into two different groups a radiation group (72 animals) and sham radiation group (36 animals). Animals were divided into smaller groups of six according to radiation dose (19 or 38 Gy or sham). Seven days before radiotherapy ampicillin 500 mg/kg/d was administered intramuscularly, in the antibiotic groups. An exteriorized segment of ileum was subjected to single high dose radiation (19 or 38 Gy). Samples were collected 2, 24, and 48 h and analyzed for microflora, MIP-2, TGF-ß, and MMP-7. RESULTS: The combination of antibiotics and irradiation leads to an early significant reduction of bacteria, down-regulates MIP-2, up-regulates TGF-ß and elevation of MMP-7 to levels achieved by antibiotics or irradiation alone. Lactobacilli were reduced to non-existent levels after antibiotics. CONCLUSIONS: Pretreatment with Ampicillin before irradiation and laparotomy in a murine model leads to Matrilysin over-expression as achieved by radiotherapy alone. Microfloral regulation does not affect MMP-7 stimulation after surgical or radiological trauma. Radiotherapy overrides the effect of antibiotics leading to an up-regulation of MMP-7, TGF-ß and MIP-2 expression between 24 h and 48 h.