Leukocyte dysfunction and reduced CTLA-4 expression are associated with perianal Crohn's disease.

Although perianal Crohn's disease (PCD) is highly associated with the exacerbated inflammation, the molecular basis and immunological signature that distinguish patients who present a history of perianal lesions are still unclear. This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for the detection of plasma cytokines and lipopolysaccharides (LPS). Peripheral blood mononuclear cells (PBMCs) were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3/anti-CD28 antibodies. Our results show that CD patients had augmented plasma interleukin (IL)-6 and LPS. However, their PBMC was characterized by decreased IL-6 production, while patients with a history of PCD produced higher IL-6, IL-8, and interferon-γ, along with decreased tumor necrosis factor alpha (TNF). CD patients had augmented FoxP3 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulatory markers, though the PCD subjects presented a significant reduction in CTLA-4 expression. CTLA-4 as well as IL-6 and TNF responses were able to distinguish the PCD patients from those who did not present perianal complications. In conclusion, IL-6, TNF, and CTLA-4 exhibit a distinct expression pattern in CD patients with a history of PCD, regardless of disease activity. These findings clarify some mechanisms involved in the development of the perianal manifestations and may have a great impact on the disease management.

Long-term effectiveness and safety of ustekinumab in bio-naïve and bio-experienced anti-tumor necrosis factor patients with Crohn's disease: a real-world multicenter Brazilian study.

BACKGROUND: The effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD) has been demonstrated in the pivotal Phase 3 UNITI 1 and 2 and IM-UNITI studies in both anti-TNF-naïve and anti-TNF-exposed patients. Given the selective nature of pivotal trial designs, real-world effectiveness and safety studies are warranted. We report our experience with UST treatment in a large, real-world multicenter cohort of Brazilian patients with CD. METHODS: We performed a retrospective multicenter study including patients with CD, predominantly biologically refractory CD, who received UST. The primary endpoint was the proportion of patients in clinical remission at weeks 8, 24 and 56. Possible predictors of clinical and biological response/remission and safety outcomes were also assessed. RESULTS: Overall, 245 CD (mean age 39.9 [15-87]) patients were enrolled. Most patients (86.5%) had been previously exposed to biologics. According to nonresponder imputation analysis, the proportions of patients in clinical remission at weeks 8, 24 and 56 were 41.0% (n = 98/239), 64.0% (n = 153/239) and 39.3% (n = 94/239), respectively. A biological response was achieved in 55.4% of patients at week 8, and 59.3% were in steroid-free remission at the end of follow-up. No significant differences in either clinical or biological remission were noted between bio-naïve and bio-experienced patients. Forty-eight patients (19.6%) presented 60 adverse events during the follow-up, of which 8 (13.3%) were considered serious adverse events (3.2% of 245 patients). Overall, a proximal disease location, younger age, perianal involvement, and smoking were associated with lower rates of clinical remission over time. CONCLUSIONS: UST therapy was effective and safe in the long term in this large real-life cohort of Brazilian patients with refractory CD, regardless of previous exposure to other biological agents.

ETV4 plays a role on the primary events during the adenoma-adenocarcinoma progression in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause of death in the world and the third in Brazil. Mutations in the APC, DCC, KRAS and TP53 genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition. METHODS: Ten paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene expression analysis. In addition, mutations in APC, KRAS and TP53 genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients. RESULTS: Gene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change> 2, p< 0.05), between the adenoma and adenocarcinoma paired samples analyzed. Gene pathway analysis using the 689 DEG identified important cancer pathways such as remodeling of the extracellular matrix and epithelial-mesenchymal transition. Among these DEG, the ETV4 stood out as one of the most expressed in the adenocarcinoma samples, further confirmed in the adenocarcinoma set of samples from the TCGA database. Subsequent in vitro siRNA assays against ETV4 resulted in the decrease of cell proliferation, colony formation and cell migration in the HT29 and SW480 colorectal cell lines. DNA sequencing analysis revealed KRAS and TP53 gene pathogenic mutations, exclusively in the adenocarcinomas samples. CONCLUSION: Our study identified a set of genes with high potential to be used as biomarkers in CRC, with a special emphasis on the ETV4 gene, which demonstrated involvement in proliferation and migration.

Increased HLA-G Expression in Tissue-Infiltrating Cells in Inflammatory Bowel Diseases.

BACKGROUND: Since HLA-G is an immune checkpoint molecule and since Crohn's disease (CD) and ulcerative colitis (UC) exhibit deregulated immune-mediated mechanisms, we aimed to evaluate intestinal HLA-G expression and soluble HLA-G (sHLA-G) levels in CD/UC patients stratified according to the CD phenotype/localization and UC extension. METHODS: HLA-G tissue expression was assessed by immunohistochemistry in biopsies collected from 151 patients (90 CD, 61 UC) and in surgical resection specimens (28 CD, 12 UC). Surgical material from 24 healthy controls was also assessed. Plasma sHLA-G levels (97 CD, 81 UC, and 120 controls) were evaluated using ELISA. RESULTS: HLA-G expression was similarly observed in the intestinal epithelial cells of control and CD/UC specimens. However, in biopsies, the plasma cells/lymphocytes infiltrating the lamina propria in CD/UC presented (1) increased HLA-G expression compared to controls (P < 0.0001), (2) greater cell staining in UC cells than in CD cells irrespective of disease extent (P = 0.0011), and (3) an increased number of infiltrating cells in the inflammatory CD phenotype compared to that in the stenosing and fistulizing phenotypes (P = 0.0407). In surgical specimens, CD/UC patients exhibited higher infiltrating cell HLA-G expression in lesion areas than in margins. sHLA-G levels were higher in UC/CD patients (P < 0.0001) than in controls, but no difference was observed between diseases. CONCLUSIONS: Increased infiltrating cell HLA-G expression associated with increased sHLA-G levels in CD/UC patients may reflect ongoing host strategies to suppress chronic inflammation.

A novel technique for superficial complicated stomas using the Dacron vascular prosthesis.

BACKGROUND AND PURPOSE: Despite the advances achieved in surgical techniques in recent years, an intestinal stoma is still needed in many patients undergoing colorectal surgery. However, the intestinal stoma may be associated with serious complications and the need for a second surgical procedure. In extreme cases, when it is not possible to access the abdominal cavity, the management of a complicated stoma is challenging. The purpose of this study was to describe the use of a Dacron vascular prosthesis (DVP) in patients with intestinal stoma complications. METHODS: In patients with a shallow, superficial stoma or mucocutaneous separation (MCS), we sutured the prosthesis in the intestinal loop (at the edge of an intestinal fistula) to create a device to direct the fecal content to the collection bag. RESULTS: We included 9 patients in this series (colorectal cancer, n = 5; Crohn's disease, n = 2; giant abdominal hernia and morbid obesity, n = 2). The results obtained were promising since they showed good evolution in patients with severe intestinal complications and an impossibility of surgical correction of the stoma. Five patients presented complete healing, and two patients presented partial healing. There were two deaths caused by sepsis, which were not related to the surgical procedure. With this technique, there was a reduction in the leakage of intestinal contents into the peritoneal cavity and an increase in the healing of the peristomal dermatitis in most of the patients. The DVP could possibly represent a surgical alternative in selected patients with complicated stomas when surgical correction may not be a suitable option. CONCLUSIONS: The authors recommend this technique for selected complex cases of stoma complications after unsuccessful attempts to adapt collecting equipment. The placement of the DVP allowed the peristomal skin to heal and improved the contamination of the peritoneal cavity.

Experimental Model of Rectal Carcinogenesis Induced by N-Methyl-N-Nitrosoguanidine in Mice with Endoscopic Evaluation.

Background and purpose: The discovery of chemical substances with carcinogenic properties has allowed the development of several experimental models of colorectal cancer (CRC). Classically, experimental models of CRC in mice have been evaluated through clinical or serial euthanasia. The present study aims to investigate the role of low endoscopy in the analysis of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Methods: Thirty C57BL6 mice were divided into two groups: a control group with fifteen animals that underwent rectal instillation of saline solution on day 0 and a carcinogen group with fifteen animals that underwent a 100 mg/kg MNNG rectal instillation on day 0. In both groups, low endoscopies were performed on weeks 4 and 8. We used a validated endoscopic scoring system to evaluate the severity of colitis and colorectal tumor. Euthanasia was carried out at week 12. Results: We observed higher inflammation scores (p <0.001) and a higher number of tumors (p <0.05) in the MNNG group than the control group, both at weeks 4 and 8. A worsening of inflammation scores from the first to the second endoscopy was also noticeable in the MNNG group. There were no bowel perforations related to the procedure, and there was one death in the control group. Conclusion: Low endoscopy in experimental animals allows safe macroscopic evaluation of colorectal carcinogenesis without the need for euthanasia.

Effect of Zinc Supplementation on Serological Response to Vaccination Against Streptococcus Pneumoniae in Patients Undergoing Chemotherapy for Colorectal Cancer.

The aim of the study was to evaluate the effect of zinc supplementation on the antibody titer and the 23-valent pneumococcal seroconversion after vaccination in patients undergoing chemotherapy for colorectal cancer. The study included 25 patients undergoing postsurgery chemotherapy for colorectal adenocarcinoma (chemo group). Subjects were assessed in the perioperative period (prevaccination), before chemotherapy (4th wk) and after 3 cycles of chemotherapy (16th wk). Thirty-two healthy volunteers (control group) were included in the study. Participants received the 23-valent pneumococcal conjugate vaccine, and capsules containing zinc (Zn) sulfate (70 mg daily) or identical placebo capsules (containing wheat starch with no added Zn) for 16 wk and were randomly allocated on one of the following groups: chemo-Zn (n = 10), chemo-placebo (n = 15), control-Zn (n = 21), and control-placebo (n = 11). The antipneumococcal antibody titer against 6 polysaccharides was analyzed by ELISA and compared using linear mixed models. The seroconversion rate was compared using Fisher's exact test. An immune response to the vaccination against pneumococcus was observed in all participants. In the 16th wk, the polysaccharide 6 concentration was lower in the chemo-Zn group [2.96 (1.74-5.03) µg/mL] compared with the Chemo-Placebo group [10.75 (5.37-21.54) µg/mL] and the seroconversion rate was lower in the chemo-placebo (36%) compared with the control-placebo (85%) (P = 0.027). Zinc supplementation did not change the antibody titer after vaccination. However, the lower seroconversion rate observed in the chemo-placebo suggests an influence of zinc in the vaccinal protection.

Access to High-Cost Biological Agents: Perceptions of Brazilian Patients with Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: Brazilian patients with inflammatory bowel diseases (IBD) requiring therapy with biological agents usually have access to medicines through the National Unified Health Care System (SUS). This study aimed to analyze Brazilian IBD patient perception regarding access (availability and provision quality) to high-cost drugs in the public health care system. METHODS: A questionnaire-based survey was carried out in an IBD referral center in Brazil. All adult patients with an established diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) that use biological therapy were invited to participate. Data were collected on the biological in use, lack of distribution (number of absences, average time to regularization, impairment in patient treatment), and difficulties reported by patients in obtaining the drugs. RESULTS: Overall, 205 patients met the inclusion criteria and answered the questionnaire. Most of the patients had CD (n = 161, 78.5%), nearly half of them (n = 104, 50.7%) were female; 87 patients (42.4%) were unemployed, and of these, 40 patients (19.5%) had government assistance as the main source of income. Regarding the medications used, infliximab (n = 128, 62.5%) was the most used medication, followed by adalimumab (n = 39, 19.0%). Most patients (n = 172, 83.9%) reported at least one failed delivery of biological medicine in the last year, with a single shortage in forty-two patients (24.4%), at least two shortages in forty-seven patients (27.3%), and three or more shortages in seventy-eight patients (45.3%). The average time to regularize the distribution was up to 1 month in 44 cases (25.6%), up to 2 months in 64 cases (37.2%), and more than 3 months in 56 patients (32.6%). Among patients who reported delays, 101 patients (58.7%) felt that it may have impaired their treatment. CONCLUSION: Brazilian IBD patients reported high rates of failure to dispense biological drugs by the national healthcare system within one year. Our data highlight the need for improvement in this system for the correct supply of medication to avoid treatment failure and relapse.

The effect of hyperbaric oxygenation on the distal intestine of rats subjected to ionizing radiation.

The current study was to test an experimental model of actinic lesions in the distal intestine of rats and to determine the possible protective effect of hyperbaric oxygen therapy (HBO2) in radio-induced lesions when concomitantly applied with ionizing radiation. Twenty-four Wistar rats were divided into four groups: G1 (control group); G2 (animals irradiated); G3 (animals irradiated plus HBO2); G4 (only HBO2). The animals were evaluated for 28 days after the end of treatment and then euthanized. The distal intestine was resected for macroscopic and microscopic evaluation and immunohistochemistry. The animals in the G3 group lost weight during the treatment; all of the animals in the G2 group presented macroscopic mucosal lesions up until 28 days; the animals in the other three groups did not present macroscopic lesions. Microscopic mucosal lesions were observed in the specimens of the animals treated with ionizing radiation; in the animals from the G3 and G4 groups the lesions were less intense. For the immunohistochemical analysis, we observed the specimens taken from G3 group animals had more CD34+ cells. The experimental model proved to be useful in causing radio-induced lesions, and concomitantly applied HBO2 is capable of reducing late actinic lesions.

COVID-19 quarantine measures are associated with negative social impacts and compromised follow-up care in patients with inflammatory bowel disease in Brazil.

BACKGROUND: COVID-19 has affected the entire world. We aimed to determine the impact of COVID-19 containment measures on the daily life and follow up of patients with inflammatory bowel disease (IBD). METHODS: During May 2020, we evaluated 179 (79.6%) patients with Crohn's disease (CD) and 46 (20.4%) with ulcerative colitis (UC) by telephone, using a structured questionnaire to gather information on social impact and IBD follow up. RESULTS: Some kind of social distancing measure was reported by 95.6% of our patients, self-quarantine (64.9%) being the most frequent. Depressive mood was the most prevalent social impact (80.2%), followed by anxiety/fear of death (58.2%), insomnia (51.4%), daily activity impairment (48%), sexual dysfunction (46.2%), and productivity impairment (44%). The results were similar when we compared patients with active disease to those in remission and patients with UC to those with CD. Analysis of IBD follow up showed that 83.1% of all patients missed an IBD medical appointment, 45.5% of the patients missed laboratory tests, 41.3% missed the national flu vaccination program, 31.3% missed any radiologic exam, 17.3% missed colonoscopy, and 16.9% failed to obtain biologic therapy prescriptions. Biologics were discontinued by 28.4% of the patients. UC patients had higher rates of missed vaccination than CD patients (56.5% vs. 37.4%, P=0.02) and more failures to obtain a biologic prescription (28.3% vs. 14.0%, P=0.02). CONCLUSIONS: Our study reveals alarming social impacts and declining follow-up care for IBD patients during the COVID-19 outbreak. These findings may have implications for disease control in the near future.

Hyperbaric oxygen on the healing of ischemic colonic anastomosis--an experimental study in rats.

The aim of the present study was to evaluate the effect of hyperbaric oxygen therapy (HBO2) on the healing process of ischemic colonic anastomoses in rats. Forty Wistar rats were divided into four groups: control (Group I), control and HBO2 (Group II), ischemia (Group III), ischemia and HBO2 (Group IV). Ischemia was achieved by clamping four centimeters of the colonic arcade. On the eighth therapy day, the anastomotic region was removed for quantification of hydroxyproline and immunohistochemical determination of metalloproteinases 1 and 9 (MMP1, MMP9). The immunohistochemical studies showed significantly larger metalloproteinase-labeled areas in Group IV compared with Group III for both MMP1 and MMP9 (p < 0.01). This finding points to a higher remodeling activity of the anastomoses in this experimental group. Additionally, animals subjected to hyperbaric oxygen therapy showed both a reduction in interstitial edema and an increase in hydroxyproline concentrations [at the anastomotic site]. Therefore, we conclude that HBO2 is indeed beneficial in anastomotic ischemia.

Preoperative rectal tumor embolization as an adjunctive tool for bloodless abdominoperineal excision: A case report.

BACKGROUND: Abdominoperineal excision (APE)-related hemorrhage can be challenging due to difficult access to pelvic organs and the risk of massive blood loss. The objective of the present study was to demonstrate the use of preoperative embolization (PE) as a strategy for blood preservation in a patient with a large low rectal tumor with a high risk of bleeding, scheduled for APE. CASE SUMMARY: A 56-year-old man presented to our institution with a one-year history of anal bleeding and rectal tenesmus. The patient was diagnosed with bulky adenocarcinoma limited to the rectum. As the patient refused any clinical treatment, surgery without previous neoadjuvant chemoradiation was indicated. The patient underwent a tumor embolization procedure, two days before surgery performed via the right common femoral artery. The tumor was successfully devascularized and no major bleeding was noted during APE. Postoperative recovery was uneventful and a one-year follow-up showed no signs of recurrence. CONCLUSION: Therapeutic tumor embolization may play a role in bloodless surgeries and increase surgical and oncologic prognoses. We describe a patient with a bulky low rectal tumor who successfully underwent preoperative embolization and bloodless abdominoperineal resection.

Neuroendocrine appendiceal tumor and endometriosis of the appendix: a case report.

INTRODUCTION: Endometriosis of the appendix is very uncommon, accounting for only about 1% of all cases of endometriosis. However, endometriosis is found in the appendix in approximately 8-13% of patients with deep infiltrating endometriosis and is particularly common in patients with severe forms of deep infiltrating endometriosis. Neuroendocrine tumors are the most common neoplasms of the appendix and may be misdiagnosed when there are multiple endometriosis lesions in the pelvis. CASE PRESENTATION: We describe a case of a Caucasian patient with deep infiltrating endometriosis with rectal involvement, retrocervical lesions, and a right ovarian endometrioma with no suspected lesions in the appendix. She underwent laparoscopy and, after a systematic intraoperative evaluation, suspected involvement of the appendix was observed. The patient underwent ovarian cystectomy, excision of the pelvic endometriosis lesions, appendectomy, and anterior stapler discoid resection. Histopathological analysis of the appendix revealed endometriosis and a well-differentiated neuroendocrine carcinoma at the appendix tip. DISCUSSION: Our patient's case emphasizes the need to approach these lesions carefully and strengthens the indication for appendectomy when the appendix is affected in the setting of endometriosis. Despite the more likely diagnosis of appendiceal endometriosis, neuroendocrine tumors cannot be ruled out by imaging examinations, and both conditions can occur in the same patient.

KRAS mutation associated with CD44/CD166 immunoexpression as predictors of worse outcome in metastatic colon cancer.

INTRODUCTION: Multiple stages of carcinogenesis in colon cancer encompass subpopulations of cancer stem cells (CSC), responsible for tumor cell transformation, growth and proliferation. CD44 and CD166 proteins are CSC markers associated with cell signaling, adhesion, migration, metastasis and lymphocytic response. The expression of CSC may be modulated by some factors, such as the KRAS gene mutation. OBJECTIVE: Correlate the expression of CD44 and CD166 markers in metastatic colon adenocarcinoma and KRAS mutation status (wild-type/mutated) with clinical pathological features and patients' outcome. MATERIAL AND METHODS: Fifty-eight samples of tumor tissue samples of metastatic colon adenocarcinoma were collected from patients treated with CapeOx at the HCFMRP-USP Clinical Oncology Service. Clinical and survival data were collected from medical records. KRAS status was determined by the polymerase chain reaction (PCR) technique, and analysis of immunohistochemical expression of CD44 and CD166 proteins was performed by tissue microarray. RESULTS: The expression of CD44 and CD166 were positive in 41% and 43% of patients, respectively, and mutated KRAS was detected in 48% of patients. A significant association was found between CD166 and CD44 expression (p= 0.016), mainly in the wild-type KRAS group (p= 0.042) and patients over 65 years (p= 0.001). CD44-positive patients had 3.7-fold and 5.3-fold greater risk of liver metastasis and lung metastasis, respectively (p< 0.01), compared with CD44-negative patients. CD166-negative patients had 2.7 greater risk of lymph node involvement (0.03), compared with CD166-positive patients. KRAS mutation increased the risk of liver metastasis by 8 times (p< 0.01), and the risk of lung metastasis by 5 times (p= 0.04) in CD44-positive patients. KRAS mutation increased the risk of lymph node involvement by 8 times in CD166-negative patients (p= 0.0007). CONCLUSION: An association between CD44 and CD166 expression was demonstrated in this study. Analysis of KRAS mutation combined with immunohistochemical expression of CD44 and CD166 identified subgroups of patients with colon adenocarcinoma at higher risk of lymph node involvement by the tumor and development of liver and lung metastasis.

Effect of Zinc Supplementation on Antioxidant Defenses and Oxidative Stress Markers in Patients Undergoing Chemotherapy for Colorectal Cancer: a Placebo-Controlled, Prospective Randomized Trial.

The study aimed to investigate the effect of oral zinc supplementation on antioxidant defenses and oxidative stress markers during chemotherapy for colorectal cancer. Twenty-four patients who had undergone surgical resection of colorectal cancer participated in this placebo-controlled, prospective randomized study. The supplementation was started in the perioperative period, in which 10 patients received 70 mg of zinc (zinc group, n = 10) and 14 patients received placebo (placebo group, n = 14) for 16 weeks. Approximately 45 days after surgical resection of tumor, all patients received a chemotherapeutic regimen (capecitabine, capecitabine combined with oxaliplatin or 5-fluorouracil). Vitamin C, vitamin E, antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), and lipid peroxidation markers malondialdehyde (MDA) and 8-isoprostane were determined before the first, second, third, and fourth chemotherapy cycles. Compared with the placebo group, the zinc group presented higher SOD values before the first, second, and fourth chemotherapy cycles and lower GPx values before the third cycle. There were no statistical differences between the study groups in vitamin C, vitamin E, MDA, or 8-isoprostane plasma values. Longitudinal analysis revealed decreased vitamin E concentration in the placebo group before the second and fourth cycles as compared with the initial values. Zinc supplementation during chemotherapy cycles increased SOD activity and maintained vitamin E concentrations. Although no effect of zinc supplementation on oxidative stress markers was observed, the increase in SOD activity indicates a production of stable free radicals, which may have a positive effect in cancer treatment.

Infliximab-associated fulminant hepatic failure in ulcerative colitis: a case report.

INTRODUCTION: Infliximab, an antibody against tumor necrosis factor alpha, is used to treat inflammatory bowel disease and has well-established efficacy and proven safety. Complications of this treatment are related to immunosuppression and include higher risk of serious infections and malignant neoplasia. Although extremely rare, fulminant liver damage related to infliximab therapy has been reported. CASE PRESENTATION: We present the case of a 38-year-old Afro-Brazilian woman with refractory ulcerative colitis who was started on infliximab. She had no previous history of liver disease, alcohol abuse, or infection. After the fifth dose of the medication, drug-induced liver injury was diagnosed. Treatment was discontinued but our patient's condition was aggravated by severe cholestasis and grade III/IV encephalopathy, requiring liver transplantation. CONCLUSION: Drug-induced liver injury is an uncommon complication of infliximab. Current consensus recommends screening for liver dysfunction prior to and during therapy. This case emphasizes the need for vigilance and highlights a rare and potentially lethal complication.

Hyperbaric oxygen therapy for primary sternal osteomyelitis: a case report.

INTRODUCTION: Primary osteomyelitis of the sternum is a rare condition, which accounts for 0.3% of all cases of osteomyelitis reported in the literature. The diagnosis requires a high degree of suspicion and confirmation by percutaneous biopsy. The treatment consists of resection of the periosteum and affected bone. Despite reports of successful conservative treatment using antibiotics alone, early surgical intervention plus bacterial control is the definitive treatment; it reduces morbidity, and is the most cost-effective approach for the patient. We report a case of primary osteomyelitis surgically treated with debridement and antibiotics, followed by hyperbaric oxygen therapy. CASE PRESENTATION: A 39-year-old Brazilian man without a significant medical history presented with primary osteomyelitis. After a normal chest radiograph and normal laboratory test results, he was treated with 2 weeks of nonsteroidal anti-inflammatory drugs. One month later a presumptive diagnosis of Tietze syndrome was made and he was prescribed prednisolone (60mg/day) for 3 weeks. The following month he presented to our service with swelling, redness, and warmth in the area between his left third and fourth ribs. Subsequent magnetic resonance imaging revealed a large collection of liquid (8.8×6.8×20.2cm) in his chest wall, between the body and the manubrium of the sternum. An area of soft, friable tissue with a large amount of pus was found in his sternum during surgical debridement. Subsequent treatment consisted of antibiotic therapy using metronidazole and cefotaxime plus hyperbaric oxygen therapy. On postoperative day 10 the incision was sutured. The patient was discharged on postoperative day 15 on a regimen of oral ciprofloxacin, and completed hyperbaric oxygen therapy as an out-patient. CONCLUSIONS: The satisfying outcome of this patient reflects the quick action to promote surgical debridement and use of antibiotics, which are both recommended treatments. The closure of the wound in 10 days after debridement suggests that the hyperbaric oxygen therapy might have indirectly, but not conclusively, aided in the premature closure of the wound, avoiding a longer healing by second intention or muscle flap rotation closure.

Clinical-Pathological Correlation of KRAS Mutation Status in Metastatic Colorectal Adenocarcinoma.

BACKGROUND: KRAS gene mutations play an important role in the carcinogenesis of colorectal tumors. However, studies that have assessed the association between KRAS gene mutation status and disease characteristics report conflicting results. To assess KRAS gene status (mutated or wild-type) and its association with the clinical, epidemiological, and histopathological features of metastatic colorectal adenocarcinoma as well its association with clinical outcomes. METHODS: Cross-sectional descriptive study in which clinical and histopathological data were collected from the medical records of 65 patients diagnosed with metastatic colorectal adenocarcinoma at the Clinical Oncology Service of the Teaching Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo -HCFMRP-USP) between 2005 and 2012 and analyzed based on their KRAS gene status. RESULTS: KRAS gene mutations were found in 49.2% of the tumors, and G/A (25.5%) and Gly12Asp (34.37%) were the most frequent mutations. Among the investigated clinical features (gender, ECOG (Eastern Cooperative Oncology Group), histology, degree of cell differentiation, lymph node ratio, primary tumor site, staging, presence of synchronous metastasis, lung metastasis, and liver metastasis), the association between age less than 65 years with KRAS mutation was statistically significant (P = 0.046). KRAS mutation status did not exhibit a significant correlation with the overall survival of the patients (P = 0.078); however, the cases with KRAS mutation exhibited shorter survival. In the multivariate analysis, synchronous metastasis (P = 0.03) and liver metastasis (P = 0.008) behaved as independent factors of poor prognosis relative to the overall survival of the patients. CONCLUSION: The KRAS mutation status did not exhibit prognostic value in the investigated sample. Among the older patients (> 65 years old), wild-type KRAS was more frequently observed compared to mutated KRAS.

Effects of preoperative pelvic irradiation on colonic anastomosis healing. An experimental study in rats.

PURPOSE: Colorectal anastomosis is a constant worry-issue among surgeons because of high rates of complications, specially the dehiscence. The preoperative irradiation on cancer surgeries might interfere in the healing process, leading to an unfavorable outcome. METHODS: In the present study, two groups of rats were irradiated previously to a colorectal anastomosis surgery, with intervals of 4 and 8 weeks between the procedures. Seven days after the surgery, healing process was evaluated for dehiscence presence and histologic inflammatory characteristics. Also, levels of hydroxyproline, metalloproteinases and vascular endothelial growth factor were measured. RESULTS: Our results showed a higher incidence of dehiscences on the animals submitted to irradiation, compared to controls, with a reduced inflammatory activity in the healing tissue. DISCUSSION: Comparing both irradiated groups, those irradiated 8 weeks before surgery showed higher levels of hydroxyproline and metalloproteinases, indicating higher efficiency of the healing process. In conclusion, preoperative irradiation interferes with intestinal anastomosis healing and a larger time interval between both procedures is safer in terms of the healing quality.