Vaginal microbial profile of cervical cancer patients receiving chemoradiotherapy: the potential involvement of Lactobacillus iners in recurrence.

The vaginal microbiome is an immune defense against reproductive diseases and can serve as an important biomarker for cervical cancer. However, the intrinsic relationship between the recurrence and the vaginal microbiome in patients with cervical cancer before and after concurrent chemoradiotherapy is poorly understood. Here, we analyzed 125 vaginal microbial profiles from a patient cohort of stage IB-IVB cervical cancer using 16S metagenomic sequencing and deciphered the microbial composition and functional characteristics of the recurrent and non-recurrent both before and after chemoradiotherapy. We demonstrated that the abundance of beneficial bacteria and stability of the microbial community in the vagina decreased in the recurrence group, implying the unique characteristics of the vaginal microbiome for recurrent cervical cancer. Moreover, using machine learning, we identified Lactobacillus iners as the most important biomarker, combined with age and other biomarkers (such as Ndongobacter massiliensis, Corynebacterium pyruviciproducens ATCC BAA-1742, and Prevotella buccalis), and could predict cancer recurrence phenotype before chemoradiotherapy. This study prospectively employed rigorous bioinformatics analysis and highlights the critical role of vaginal microbiota in post-treatment cervical cancer recurrence, identifying promising biomarkers with prognostic significance in the context of concurrent chemoradiotherapy for cervical cancer. The role of L. iners in determining chemoradiation resistance in cervical cancer warrants further detailed investigation. Our results expand our understanding of cervical cancer recurrence and help develop better strategies for prognosis prediction and personalized therapy.

Live attenuated bacterium limits cancer resistance to CAR-T therapy by remodeling the tumor microenvironment.

The tumor microenvironment (TME) is characterized by the activation of immune checkpoints, which limit the ability of immune cells to attack the growing cancer. To overcome immune suppression in the clinic, antigen-expressing viruses and bacteria have been developed to induce antitumor immunity. However, the safety and targeting specificity are the main concerns of using bacteria in clinical practice as antitumor agents. In our previous studies, we have developed an attenuated bacterial strain (Brucella melitensis 16M ∆vjbR, henceforth Bm∆vjbR) for clinical use, which is safe in all tested animal models and has been removed from the select agent list by the Centers for Disease Control and Prevention. In this study, we demonstrated that Bm∆vjbR homed to tumor tissue and improved the TME in a murine model of solid cancer. In addition, live Bm∆vjbR promoted proinflammatory M1 polarization of tumor macrophages and increased the number and activity of CD8+ T cells in the tumor. In a murine colon adenocarcinoma model, when combined with adoptive transfer of tumor-specific carcinoembryonic antigen chimeric antigen receptor CD8+ T cells, tumor cell growth and proliferation was almost completely abrogated, and host survival was 100%. Taken together, these findings demonstrate that the live attenuated bacterial treatment can defeat cancer resistance to chimeric antigen receptor T-cell therapy by remodeling the TME to promote macrophage and T cell-mediated antitumor immunity.

Disruption of the oral microbiota is associated with a higher risk of relapse after allogeneic hematopoietic stem cell transplantation.

Intestinal microbiota (IM) diversity and composition regulates host immunity and affects outcomes after allogeneic stem cell transplantation (allo-HSCT). We evaluated if the oral mucosa microbiota (OM) could impact the outcomes in patients who underwent allo-HSCT. Samples from the oral mucosa of 30 patients were collected at three time points: before the conditioning regimen, at aplasia, and at engraftment. We analyzed the associations of OM diversity and composition with allo-HSCT outcomes. Lower OM diversity at preconditioning was associated with a higher risk of relapse at 3 years (68% versus 33%, respectively; P = 0.04). Dominance (relative abundance ≥ 30%) by a single genus at preconditioning was also associated with a higher risk of relapse (63% versus 36% at 3 years, respectively; P = 0.04), as well as worse progression-free survival (PFS; 19% versus 55%, respectively; P = 0.01), and overall survival (OS) at 3 years (38% versus 81%, respectively; P = 0.02). In our study we observed that OM dysbiosis is associated with a higher risk of relapse and worse survival after allo-HSCT.

Lower airway bacterial microbiome may influence recurrence after resection of early-stage non-small cell lung cancer.

OBJECTIVE: The lower airway bacterial microbiome influences carcinogenesis and response to immunotherapy in non-small cell lung cancer (NSCLC). We investigated the association of this microbiome with recurrence in early NSCLC. METHODS: Microbiomes of presurgery bronchoalveolar lavage (BAL) and saliva, and resected stage I NSCLC tumor and adjacent lung tissues of 48 patients were examined by 16S gene sequencing. Tumor gene expression was measured by RNA sequencing. RESULTS: Spatial relationships of the different biospecimen types was reflected in their microbiomes, with microbiomes of BAL intermediate to those of saliva and lung tissue. BAL and saliva microbiomes were less dissimilar in patients with high α-amylase levels in BAL, indicating oral aspiration as a source of lower airway microbiota. BAL microbiomes of patients with recurrence within 32 months of surgery differed from those without recurrence during ≥32 months of follow-up (n = 18 each), despite no difference for age, sex, smoking history, and tumor histology and grade. The recurrence-associated BAL microbiome signature was present in 16 of the 18 recurrence cases but in only two of the others. Signature presence was associated with shorter recurrence-free survival (log-rank test P < .001; hazard ratio = 14.5), and greater expression in tumors of genes for cell proliferation and epithelial mesenchymal transition. Immune cellular composition of the tumor microenvironment was not different between patients with and without the signature. CONCLUSIONS: Presurgery composition of lower airway microbiome may be associated with recurrence of early NSCLC. This association may reflect an influence of the microbiome on tumor biology.

The relationship between post-surgery infection and breast cancer recurrence.

Breast cancer is the second most prevalent form of cancer in women worldwide, with surgery remaining the standard treatment. The adverse impact of the surgery remains controversial. It has been suggested that systemic factors during the postoperative period may increase the risk of recurrence, specifically surgical site infection (SSI). The aim of this review was to critically appraise current published literature regarding the influence of SSIs, after primary breast cancer surgery, on breast cancer recurrence, and to delve into potential links between these. This systematic review adopted two approaches: to identify the incidence rates and risk factors related to SSI after primary breast cancer surgery; and, secondly, to examine breast cancer recurrence following SSI occurrence. Ninety-nine studies with 484,605 patients were eligible in the SSI-focused searches, and 53 studies with 17,569 patients for recurrence-focused. There was a 13.07% mean incidence of SSI. Six-hundred and thirty-eight Gram-positive and 442 Gram-negative isolates were identified, with methicillin-susceptible Staphylococcus aureus and Escherichia coli most commonly identified. There were 2077 cases of recurrence (11.8%), with 563 cases of local recurrence, 1186 cases of distant and 25 cases which recurred both locally and distantly. Five studies investigated the association between SSI and breast cancer recurrence with three concluding that an association did exist. In conclusion, there is association between SSI and adverse cancer outcomes, but the cellular link between them remains elusive. Confounding factors of retrospective study design, surgery type and SSI definition make results challenging to compare and interpret. A standardized prospective study with appropriate statistical power is justified.

Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes.

Colorectal cancer (CRC) is a multifaceted disease influenced by both environmental and genetic factors. A large body of literature has demonstrated the role of gut microbes in promoting inflammatory responses, creating a suitable microenvironment for the development of skewed interactions between the host and the gut microbiota and cancer initiation. Even if surgery is the primary therapeutic strategy, patients with advanced disease or cancer recurrence after surgery remain difficult to cure. Therefore, the gut microbiota has been proposed as a novel therapeutic target in light of recent promising data in which it seems to modulate the response to cancer immunotherapy. The use of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics, and fecal microbiota transplantation, is therefore considered to support current therapies in CRC management. In this review, we will discuss the importance of host-microbe interactions in CRC and how promoting homeostatic immune responses through microbe-targeted therapies may be useful in preventing/treating CRC development.

Correlation between healing type of lesion and recurrence in gastric neoplastic lesions after endoscopic submucosal dissection.

BACKGROUND/AIMS: To date, there are few reports on the clinical association between healing pattern of lesion and local recurrence after endoscopic resection (ER). We examined the risk factors associated with local recurrence after endoscopic submucosal dissection (ESD) and the correlation between healing type of lesion and recurrence. MATERIALS AND METHODS: We retrospectively analyzed medical records of 293 patients who underwent ESD of early gastric cancer or gastric adenoma between April 2010 and January 2012. We analyzed the relationship among factors such as age, location of lesion, size, pathologic diagnosis, presence of Helicobacter pylori (H. pylori), and healing types of ulcers in patients with local recurrence through follow-up endoscopic surveillance (1, 6, and 12 months after ESD). RESULTS: We analyzed 141 patients except for patients who had not undergone surveillance endoscopy, H. pylori test, and ambiguous healing patterns. There were no significant correlations between local recurrences concerning sex, age, tumor size, location, and pathologic diagnosis. When the healing type of the ulcer was divided into hypertrophic polypoid type (9 cases (6.4%)), scar type (122 cases (86.5%)), and nodular type (10 cases (7.1%)), the scar type was found to be most common. A total of eight patients (5.7%) developed local recurrence, of which five were of nodular type and statistically significant (p=0.000). CONCLUSION: The most common type of ulcer healing was scar type after ESD, but nodular type was associated with local recurrence. When we perform follow-up endoscopy after ESD, we should pay attention to the lesion that has nodular change of mucosal surface.

Transfusion of red blood cells does not impact progression-free and overall survival after surgery for ovarian cancer.

BACKGROUND: Allogeneic red blood cells (RBCs) have the potential to impact the immunosurveillance of the recipient and may therefore increase the risk of recurrence after cancer surgery. In this article the relationship between perioperative RBC transfusion and the risk of recurrence after ovarian cancer surgery is examined. STUDY DESIGN AND METHODS: This is a retrospective cohort analysis of a prospective database of patients who underwent surgery due to primary ovarian cancer between 2006 and 2014 and who had no residual disease after surgery. Patients who did and did not receive perioperative RBC transfusion were compared. The primary endpoint was progression-free survival (PFS). Propensity score matching (PSM) and Cox proportional hazards regression (CPH) was used to control for between-group differences of prognostic determinants. RESULTS: A total of 529 patients with a median follow-up of 51.4 months (95% CI, 46.1-56.5) were eligible for analysis. Of those, 408 patients (77.1%) received allogeneic, leukoreduced RBCs with a median of 4 units (IQR, 2-6) per patient. There was a strong selection bias of prognostic determinants between patients with and without transfusion. In unadjusted analysis, transfusion of RBCs was associated with an increased risk of cancer recurrence (hazard ratio [HR] of PFS 2.71 [95% CI, 1.94-3.77], p < 0.001). After bias reduction, transfusion of RBCs was no longer associated with an increased risk of cancer recurrence, neither in PSM-adjusted (HR 1.03 [95% CI, 0.59-1.80], p = 0.91), nor in multivariable CPH-adjusted analysis (HR 1.26 [95% CI, 0.85-1.86], p = 0.23). CONCLUSION: Perioperative transfusion of RBCs did not increase the risk of recurrence after ovarian cancer surgery.

Comparison of the Clinicopathological Characteristics and Genetic Alterations Between Patients with Gastric Cancer with or Without Helicobacter pylori Infection.

BACKGROUND: Helicobacter pylori (HP) can induce epithelial cells and intestinal metaplasia with genetic damage that makes them highly susceptible to the development of gastric cancer (GC). MATERIALS AND METHODS: Between 2005 and 2010, 356 patients with gastric cancer who received curative surgery were enrolled. Analysis of HP, Epstein-Barr virus (EBV) infection, PIK3CA amplification, and mutation analysis of 68 mutations in eight genes using a mass spectrometric single-nucleotide polymorphism genotyping technology was conducted. The clinicopathological characteristics of patients with or without HP infection were compared. RESULTS: Among the 356 patients, 185 (52.0%) had HP infection. For intestinal-type GC, patients with HP infection were more likely to be younger and had fewer PI3K/AKT pathway genetic mutations than those without HP infection. For diffuse-type GC, patients with HP infection were characterized by less male predominance, less lymphoid stroma, fewer microsatellite instability-high tumors, and fewer PI3K/AKT pathway genetic mutations than those without HP infection. Patients with HP infection had less tumor recurrence and a better 5-year overall survival (87.7% vs. 73.9%, p = .012) and disease-free survival (64.1% vs. 51.3%, p = .013) than those without HP infection, especially for intestinal-type GC. For EBV-negative GC, patients with HP infection had fewer PI3K/AKT pathway mutations and a better 5-year overall survival and disease-free survival than those without HP infection. Multivariate analysis demonstrated that HP infection was an independent prognostic factor regarding overall survival and disease-free survival. CONCLUSION: Patients with GC with HP infection were associated with fewer PI3K/AKT pathway genetic mutations and better survival than those without HP infection, especially for EBV-negative and intestinal-type GC. IMPLICATIONS FOR PRACTICE: Patients with gastric cancer with Helicobacter pylori (HP) infection had fewer PI3K/AKT pathway genetic mutations, less tumor recurrence, and better survival than those without HP infection, especially for Epstein-Barr virus (EBV)-negative and intestinal-type gastric cancer. HP infection is an independent prognostic factor regarding overall survival and disease-free survival. Future in vivo and in vitro studies of the correlation among HP infection, PI3K/AKT pathway, and EBV infection in gastric cancer are required.

Gut microbiome influences on anastomotic leak and recurrence rates following colorectal cancer surgery.

BACKGROUND: The pathogenesis of colorectal cancer recurrence after a curative resection remains poorly understood. A yet-to-be accounted for variable is the composition and function of the microbiome adjacent to the tumour and its influence on the margins of resection following surgery. METHODS: PubMed was searched for historical as well as current manuscripts dated between 1970 and 2017 using the following keywords: 'colorectal cancer recurrence', 'microbiome', 'anastomotic leak', 'anastomotic failure' and 'mechanical bowel preparation'. RESULTS: There is a substantial and growing body of literature to demonstrate the various mechanisms by which environmental factors act on the microbiome to alter its composition and function with the net result of adversely affecting oncological outcomes following surgery. Some of these environmental factors include diet, antibiotic use, the methods used to prepare the colon for surgery and the physiological stress of the operation itself. CONCLUSION: Interrogating the intestinal microbiome using next-generation sequencing technology has the potential to influence cancer outcomes following colonic resection.

Bacteremia due to Capnocytophaga species during chemotherapy-induced neutropenia in patients with hematological malignancies.

The number of reported cases of infections due to Capnocytophaga species (spp.) is limited. We herein describe four cases developing bacteremia due to Capnocytophaga spp. during neutropenia after chemotherapy for hematological malignancies. At the onset of bacteremia, 3 of the 4 patients had oral mucositis, and 2 were co-infected with other bacteria. Two patients developed bacteremia while receiving fluoroquinolone as prophylaxis against bacterial infection. Bacteremia resolved with administration of antimicrobial agents in all patients and no recurrences were observed thereafter. The emergence of fluoroquinolone-resistant or beta-lactamase-producing Capnocytophaga spp. has recently been reported. Therefore, Capnocytophaga spp. could be causative pathogens in breakthrough and refractory infections under fluoroquinolone prophylaxis and empiric therapy, respectively, for febrile neutropenia. Capnocytophaga spp. should be recognized as one of the causative pathogens of febrile neutropenia. Furthermore, accumulation of cases and susceptibility data are required to establish an optimal treatment protocol.

Squamous cell carcinoma in chronic osteomyelitis: a case report and review of the literature.

BACKGROUND: Chronic osteomyelitis is a challenging problem, and malignant transformation is a rare occurrence. We report a case of a patient with squamous cell carcinoma arising from an osteomyelitic hotbed and discuss through a literature review the etiopathogenesis, diagnosis, and treatment of this lesion. CASE PRESENTATION: A 69-year-old Italian man had sustained an exposed tibial fracture 40 years ago during a road accident, for which he had undergone various surgical osteosynthesis treatments with multiple antibiotic therapies. He presented to our hospital because of recurrence of a fistula at the proximal third of the anterior region of the tibia. For 2 months, we treated the lesion with antibiotics, and local medication with curettage. We saw no evidence of lesion improvement, and we advised the patient to undergo a knee amputation, which he refused. The alternative we chose was a surgical toilet of the osteomyelitic hotbed and used bioglass as a bone substitute. After 2 months of follow-up, we noticed a fulminating, budding formation in the area of the surgical wound that turned out to be a squamous cell carcinoma on biopsy. The patient again refused the amputation and underwent a wide-margin surgical debridement. After 2 months, the carcinoma recurred, and an above-the-knee amputation was performed. CONCLUSIONS: Our experience with this case indicates that amputation is the most appropriate treatment for squamous carcinoma occurring in patients with chronic osteomyelitis. To avoid risks of lymphonodular and organ metastasization, this radical surgical procedure should not be delayed. Early diagnosis and timely therapy can prevent amputation only in selected cases. Surgeons who treat osteomyelitis and chronic wounds should be aware of the risk of tumor degeneration. Squamous cell carcinoma associated with chronic osteomyelitis has a low-grade malignancy, but implications of lymphonodular involvement and organ metastasis should not be excluded.

Subcutaneous phaeohyphomycosis caused by Exophiala spinifera in a European patient with lymphoma: a rare occurrence case report and literature review.

Exophiala spinifera is a dematiaceous fungus responsible for rare skin infections presenting as phaeohyphomycosis or chromoblastomycosis which has been primarily reported in tropical and subtropical areas (Asia, South and North America). We report the first case of E. spinifera phaeohyphomycosis in a European patient. The phaeohyphomycosis was limited to the skin, involving the finger of an immunocompromised patient presenting with a large B-cell lymphoma treated by R-mini-CHOP regimen. Remission was initially achieved by surgical excision; however, a local subcutaneous relapse required treatment with itraconazole. We performed a literature review of the 32 previously published cases of E. spinifera phaeohyphomycosis highlighting its clinical phenotype: disseminated infection with extracutaneous involvement and poor prognosis were reported in young patients, of whom some were recently associated with CARD9 mutations, whereas cases in older immunocompromised patients were limited to the skin and showed better prognosis. There is currently no standard treatment for E. spinifera phaeohyphomycosis; however, itraconazole, alone or in combination, allowed partial or complete response in 16 out of 20 cases.

Predictive Value of NRAMP1 and HGPX1 Gene Polymorphism for Maintenance BCG Response in Non-muscle-invasive Bladder Cancer.

AIM: To assess the potential predictive value of natural resistance-associated macrophage protein 1 (NRAMP1) and human glutathione peroxidase 1 (hGPX1) polymorphism in non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin (BCG) instillation, we conducted an original ancillary multicenter study. PATIENTS AND METHODS: We evaluated patients included in the multicenter URO-BCG 4 trial, who received three weekly instillations of one-third dose BCG every 6 months (group I) or two weekly instillations every 3 months (group II) for 3 years. For clinical evaluation we also evaluated tumor recurrence and muscle progression. NRAMP1 and hGPX1 polymorphism analyses were performed on blood DNA. NRAMP1 exon 15 and hGPX1 exon 1c were amplified using Type-it Microsatellite PCR Kit® for multiplex polymerase chain reaction. RESULTS: From June 2004 to April 2010, 146 randomized patients were included in this retrospective study. Blood samples were obtained from 107 patients. With 36 months of follow-up, 13.6% of patients had a tumor recurrence and muscle-invasive progression was observed in 4.3% of patients. Concerning NRAMP1 D543N polymorphism, patients with allele A had no tumor recurrence or muscle-invasive progression. No significant difference was observed in gene polymorphism distribution between groups I and II. Moreover, we did not observe any significant association of gene polymorphisms, tumor recurrence or muscle-invasive progression, event time and disease-free survival. CONCLUSION: Our results suggest that no significant difference was found for NRAMP1 and hGPX1 gene polymorphisms associated with recurrence time, muscle invasion frequency and disease-free survival, nevertheless, we observed that the NRAMP1 D543N GG genotype group had a shorter time to tumor recurrence.

Effect of Helicobacter pylori Eradication on Long-Term Survival after Distal Gastrectomy for Gastric Cancer.

PURPOSE: Negative Helicobacter pylori status has been identified as a poor prognostic factor for survival in gastric cancer (GC) patients who underwent surgery. The aim of this study was to examine the effect of H. pylori eradication on long-term outcomes after distal gastrectomy for GC. MATERIALS AND METHODS: We analyzed the survival of 169 distal GC patients enrolled in a prospective randomized trial evaluating histologic changes of gastric mucosa after H. pylori eradication in the remnant stomach. The outcomes measured were overall survival (OS) and GC recurrence rates. RESULTS: The median follow-up duration was 9.4 years. In the modified intention-to-treat analysis including patients who underwent H. pylori treatment (n=87) or placebo (n=82), 5-year OS rates were 98.9% in the treatment group and 91.5% in the placebo group, and Kaplan-Meier analysis showed no significant difference in OS (p=0.957) between groups. In multivariate analysis, no difference in overall mortality was observed between groups (adjusted hazard ratio [aHR] for H. pylori treatment, 0.75; p=0.495) or H. pylori-eradicated status (aHR for positive H. pylori status, 1.16; p=0.715), while old age, male sex, and advanced stage ≥ IIIa were independent risk factors. Six patients in the treatment group (6.9%) and seven patients in the placebo group (8.5%) had GC recurrences, and GC recurrence rates were not different according to H. pylori treatment (5-year GC recurrence rates, 4.6% in the treatment group vs. 8.5% in the placebo group; p=0.652). CONCLUSION: H. pylori eradication for GC patients who underwent distal gastrectomy did not compromise long-term survival after surgery.

Helicobacter pylori Eradication Prevents Metachronous Gastric Neoplasms after Endoscopic Resection of Gastric Dysplasia.

PURPOSE: There is insufficient data about the role of eradication of H. pylori after endoscopic resection (ER) for gastric dysplasia. The aim was to investigate the benefit of H. pylori eradication after ER in patients with gastric dysplasia to prevent metachronous gastric neoplasms. MATERIALS AND METHODS: We retrospectively reviewed 1872 patients who underwent ER of gastric dysplasia. We excluded patients with a follow-up period of <2 years or who had not undergone tests for active H. pylori infection. A total of 282 patients were enrolled. The patients were categorized into those without active H. pylori infection (H. pylori-negative group, n = 124), those who successfully underwent H. pylori eradication (eradicated group, n = 122), and those who failed or did not undergo H. pylori eradication (persistent group, n = 36). RESULTS: Metachronous recurrence was diagnosed in 36 patients, including 19 in the H. pylori-negative group, 10 in the eradicated group, and 7 in the persistent group. The cumulative incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group in comparison with either of the H. pylori-persistent (non-eradicated or failed) groups (p = 0.039). Similarly, the incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group compared with the H. pylori-negative group (p = 0.041). CONCLUSION: Successful H. pylori eradication may reduce the development of metachronous gastric neoplasms after ER in patients with gastric dysplasia.

[HPV infection in oral, pharyngeal and laryngeal papillomas]. / HPV-Infektion in oralen, pharyngealen und laryngealen Papillomen.

BACKGROUND: HPV infections play a major role in the pathogenesis of squamous cell carcinomas of the head and neck. Regarding benign papillomas, the role of HPV is still uncertain. MATERIALS AND METHODS: To clarify this issue, 100 exophytic papillomas of the oral cavity, pharynx and larynx were subjected to histopathological and molecular pathological examination. Excision biopsies were taken from 62 male and 38 female patients with an age range of 18 to 87 years. Biopsies were tested for p16 expression by immunohistochemistry and analyzed for HPV subtypes 6/11 (low-risk), 16/18 and 31/33/53 (high-risk) by chromogenic in situ hybridization. RESULTS: HPV infections were verified molecularly in 34 % of biopsies; in all cases with the low-risk HPV subtypes 6/11. Only one case showed infection with both 6/11 and 31/33/53 subtypes, but not subtype 16/18; whereas expression of p16 was found in 67 %. The rate of positive molecular verification of HPV infection (in situ hybridization) was highest in the laryngeal lesions with 61.1 %, followed by the oral cavity with 52.9 %, and lowest in pharyngeal lesions (21.5 %). Recurrent papillomas were seen in 18 cases (18 %), of which 14 were molecularly positive for HPV (in situ hybridization). A correlation between inflammatory infiltration and HPV infection could be verified in 82 %. CONCLUSION: Our data demonstrate an important role of HPV infection for the development of benign papillomas of the head and neck region. Furthermore, there is a positive correlation between HPV infection and recurrent papillomas. Therefore, a molecular morphological HPV analysis of papillomas could provide important prognostic data.

Immunohistochemical detection of Helicobacter pylori without association of TLR5 expression in oral squamous cell carcinoma.

BACKGROUND: Approximately 15% of human deaths from cancer are associated with chronic viral or bacterial infections. Helicobacter pylori (HP), a flagellated, Gram-negative, spiral, microaerophilic bacteria is considered to be the most common chronic bacterial infection in humans. Toll-like receptor 5 (TLR5) is involved in recognition of bacterial flagella and is thought to promote tumour growth through inflammation-dependent mechanisms in epithelial cells. METHODS: Expression of HP and TLR5 was analysed in OSCC specimen (n = 191) by immunohistochemistry. TLR5 expression specificity was conducted by Western blotting in cancer cell lines (BICR3, BICR56). TLR5-stained sections were scanned and digitally analysed using ImageJ and the immunomembrane plug-in. HP expression and TLR5 expression were associated with clinicopathological characteristics and impact on survival. RESULTS: Helicobacter pylori detection was significantly associated with recurrence of the tumour, whereas TLR5 expression was not. Multivariate analysis demonstrated HP expression as an independent prognostic factor (P = 0.0260). TLR5 specificity was confirmed by Western blot analysis. CONCLUSIONS: For the first time, this study provides evidence that immunohistochemically detected HP expression in OSCC is associated with reduced disease-free survival in a large patient cohort. Although TLR5 was not associated with any clinicopathological characteristics or impact on survival, investigation of the TLR family seems to be reasonable due to the possible existence of other pathogenic bacterial or viral compounds in oral cavity cancer.

Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk.

BACKGROUND: Metachronous gastric cancer (GC) can develop after endoscopic resection of GC and cannot be predicted based on clinical signature. Aberrant DNA methylation in noncancerous gastric mucosa is strongly implicated in gastric carcinogenesis and could be a useful biomarker of GC risk. We evaluated the clinical utility of DNA methylation as a biomarker of metachronous GC risk. METHOD: We carried out scheduled follow-up endoscopy in 129 patients after curative endoscopic resection of GC. Biopsy specimens were collected from noncancerous mucosa in the gastric antrum and body, after which quantitative methylation analysis of miR-34b/c, SFRP1, SFRP2, SFRP5, DKK2 and DKK3 was carried out using bisulfite pyrosequencing. The utility of the methylation for predicting the risk of metachronous GC development was assessed using Kaplan-Meier and Cox proportional hazards model analyses. RESULTS: During the follow-up period, 17 patients (13%) developed metachronous GCs. The cumulative incidence of metachronous GC was significantly higher among patients with elevated miR-34b/c, SFRP2 and DKK2 methylation in their gastric body. MiR-34b/c showed the strongest association with the risk of metachronous GC, and the cumulative incidence of metachronous GC was much higher in the high-miR-34b/c-methylation group than the low-methylation group. Multivariate analysis adjusted for age, sex, H. pylori status and pathological findings showed miR-34b/c methylation in gastric body to be an independent predictor of metachronous GC risk. CONCLUSION: Our results suggest that methylation of miR-34b/c in the mucosa of the noncancerous gastric body may be a useful biomarker for predicting the risk of metachronous GC.

Osteomyelitis of the femur mimicking bone tumors: a review of 10 cases.

BACKGROUND: The clinical symptoms and radiographic appearance of osteomyelitis can mimic those of bone tumors. METHODS: We reviewed 10 patients with osteomyelitis of the femur who were initially diagnosed as having bone tumors and were subsequently transferred to our institution. RESULTS: Nocturnal pain of moderate intensity occurred in seven patients, and all 10 patients had elevated C-reactive protein levels. The radiographic findings included the following: a permeative, moth-eaten osteolytic lesion in six patients, an osteolytic lesion with sclerotic borders in three patients, and cortical destruction with pathological fracture in one patient. Magnetic resonance imaging was performed for eight patients, and only one had a positive penumbra sign. All patients underwent a surgical biopsy to confirm the final diagnosis for histological analysis and cultures. Klebsiella pneumoniae was detected in six patients and Staphylococcus aureus, the most common organism in osteomyelitis, was detected in three. Recurrence of infection occurred in five patients following debridement surgery; of these three had a Klebsiella pneumoniae infection. All patients received antibiotic treatment for an average of 20.4 weeks (range, 4 to 44) and surgical treatment an average of 1.8 times (range, 1 to 4). At the final follow-up, all patients were fully recovered with no signs of infection. CONCLUSIONS: When used in combination, clinical examinations, laboratory data, and radiographic findings can reliably distinguishing osteomyelitis from bone tumors.