Elizabeth M. Hechenbleikner

Microbiota organization is a distinct feature of proximal colorectal cancers

Significance We demonstrate, to our knowledge for the first time, that bacterial biofilms are associated with colorectal cancers, one of the leading malignancies in the United States and abroad. Colon biofilms, dense communities of bacteria encased in a likely complex matrix that contact the colon epithelial cells, are nearly universal on right colon tumors. Most remarkably, biofilm presence correlates with bacterial tissue invasion and changes in tissue biology with enhanced cellular proliferation, a basic feature of oncogenic transformation occurring even in colons without evidence of cancer. Microbiome profiling revealed that biofilm communities on paired normal mucosa cluster with tumor microbiomes but lack distinct taxa differences. This work introduces a previously unidentified concept whereby microbial community structural organization exhibits the potential to contribute to disease progression. Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC.

The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients

BACKGROUND Enterotoxigenic Bacteroides fragilis (ETBF) produces the Bacteroides fragilis toxin, which has been associated with acute diarrheal disease, inflammatory bowel disease, and colorectal cancer (CRC). ETBF induces colon carcinogenesis in experimental models. Previous human studies have demonstrated frequent asymptomatic fecal colonization with ETBF, but no study has investigated mucosal colonization that is expected to impact colon carcinogenesis. METHODS We compared the presence of the bft gene in mucosal samples from colorectal neoplasia patients (cases, n = 49) to a control group undergoing outpatient colonoscopy for CRC screening or diagnostic workup (controls, n = 49). Single bacterial colonies isolated anaerobically from mucosal colon tissue were tested for the bft gene with touch-down polymerase chain reaction. RESULTS The mucosa of cases was significantly more often bft-positive on left (85.7%) and right (91.7%) tumor and/or paired normal tissues compared with left and right control biopsies (53.1%; P = .033 and 55.5%; P = .04, respectively). Detection of bft was concordant in most paired mucosal samples from individual cases or controls (75% cases; 67% controls). There was a trend toward increased bft positivity in mucosa from late- vs early-stage CRC patients (100% vs 72.7%, respectively; P = .093). In contrast to ETBF diarrheal disease where bft-1 detection dominates, bft-2 was the most frequent toxin isotype identified in both cases and controls, whereas multiple bft isotypes were detected more frequently in cases (P ≤ .02). CONCLUSIONS The bft gene is associated with colorectal neoplasia, especially in late-stage CRC. Our results suggest that mucosal bft exposure is common and may be a risk factor for developing CRC.

Metabolism Links Bacterial Biofilms and Colon Carcinogenesis

Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N(1), N(12)-diacetylspermine in both biofilm-positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N(1), N(12)-diacetylspermine levels to those seen in biofilm-negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression.

Acquired rectourethral fistulas in adults: a systematic review of surgical repair techniques and outcomes.

BACKGROUND: Rectourethral fistulas are uncommon. Retrospective studies and case reports have highlighted various approaches for surgical repair. Because clinical presentations and technical expertise vary widely, no single procedure has been universally adopted. OBJECTIVE: We sought to qualitatively analyze studies describing surgical techniques and outcomes in adult acquired rectourethral fistulas to outline universal approaches for evaluation and management. DATA SOURCES: MEDLINE (PubMed, Ovid) and the Cochrane Library were searched by using the terms rectourethral fistulas, recto-urethral fistulas, urethrorectal fistulas, and prostatourethral-rectal fistulas. STUDY SELECTION: All studies were retrospective, in English, and reported at least 4 cases. Any series with >50% congenital cases or <50% adults (19+ years) was excluded. Of the 569 records identified, 26 articles were included. INTERVENTION: The intervention was surgical repair of rectourethral fistula. MAIN OUTCOME MEASURES: The main outcome measures were successful fistula closure, fistula recurrence or persistence, and permanent fecal and/or urinary diversion. RESULTS: Four hundred sixteen patients were identified, including 169 (40%) who had previous pelvic irradiation and/or ablation. Most patients (90%) underwent 1 of 4 categories of repair: transanal (5.9%), transabdominal (12.5%), transsphincteric (15.7%), and transperineal (65.9%). Tissue interposition flaps, predominantly gracilis muscle, were used in 72% of repairs. The fistula was successfully closed in 87.5%. Overall permanent fecal and/or urinary diversion rates were 10.6% and 8.3%. Most high-volume centers (≥25 patients) performed transperineal repairs with tissue flaps in 100% of cases. LIMITATIONS: This review was limited by the heterogeneity of repairs and bias toward preferred surgical approaches in single-center studies. CONCLUSIONS: Regardless of complexity, rectourethral fistulas have an initial closure rate approaching 90% when the transperineal approach is used. Permanent fecal and/or urinary diversion should be a last resort in patients with devastated, nonfunctional fecal and urinary systems.

Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria

Biofilms provide refuge for cancerous bacteria Familial adenomatous polyposis (FAP) causes benign polyps along the colon. If left untreated, FAP leads to a high incidence of colon cancer. To understand how polyps influence tumor formation, Dejea et al. examined the colonic mucosa of FAP patients. They discovered biofilms containing the carcinogenic versions of the bacterial species Escherichia coli and Bacteroides fragilis. Colon tissue from FAP patients exhibited greater expression of two bacterial genes that produce secreted oncotoxins. Studies in mice showed that specific bacteria could work together to induce colon inflammation and tumor formation. Science, this issue p. 592 Bacterial biofilms are linked to colon cancer. Individuals with sporadic colorectal cancer (CRC) frequently harbor abnormalities in the composition of the gut microbiome; however, the microbiota associated with precancerous lesions in hereditary CRC remains largely unknown. We studied colonic mucosa of patients with familial adenomatous polyposis (FAP), who develop benign precursor lesions (polyps) early in life. We identified patchy bacterial biofilms composed predominately of Escherichia coli and Bacteroides fragilis. Genes for colibactin (clbB) and Bacteroides fragilis toxin (bft), encoding secreted oncotoxins, were highly enriched in FAP patients’ colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with E. coli (expressing colibactin), and enterotoxigenic B. fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacterial strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.

Increasing the Options for Management of Large and Complex Chronic Wounds With a Scalable, Closed-System Dressing for Maggot Therapy

As reconstructive specialists, burn surgeons are often involved in managing large wounds of various etiologies. Such wounds can pose a management challenge, especially if they are chronic or occur in the setting of critical illness or multiple medical comorbidities. Medical maggots are an effective, selective, and low-risk method for wound debridement. However, their use in large and geometrically complex wounds is limited by the lack of scalability in currently available dressings, which are appropriate for smaller wounds but become cumbersome and ineffective in larger ones. This report describes a novel dressing designed for application of maggot debridement therapy in large and complex wounds. The authors then discuss how use of this dressing may create new management strategies for such wounds by allowing maggots to mechanically debride big, infected wounds. They describe the construction of a maggot containment dressing based on modified components from a negative pressure wound therapy system and provide a case report highlighting its successful clinical use in a large contaminated chronic wound resulting from Fournier’s gangrene. In the case described, the novel dressing provided scalability, containment of maggots, control of secretions, and ease of use. The dressing created an environment suitable for maggot survival and allowed effective debridement of a heavily contaminated groin wound. The novel dressing described is shown to function appropriately, allowing controlled use of maggots for effective debridement of large, irregular wounds. Facilitating the use of maggots in such wounds may broaden the algorithm for their management.

Implementation of surgical quality improvement: auditing tool for surgical site infection prevention practices.

BACKGROUND: Surgical site infections are a potentially preventable patient harm. Emerging evidence suggests that the implementation of evidence-based process measures for infection reduction is highly variable. OBJECTIVE: The purpose of this work was to develop an auditing tool to assess compliance with infection-related process measures and establish a system for identifying and addressing defects in measure implementation. DESIGN: This was a retrospective cohort study using electronic medical records. SETTING: We used the auditing tool to assess compliance with 10 process measures in a sample of colorectal surgery patients with and without postoperative infections at an academic medical center (January 2012 to March 2013). PATIENTS: We investigated 59 patients with surgical site infections and 49 patients without surgical site infections. MAIN OUTCOME MEASURES: First, overall compliance rates for the 10 process measures were compared between patients with infection vs patients without infection to assess if compliance was lower among patients with surgical site infections. Then, because of the burden of data collection, the tool was used exclusively to evaluate quarterly compliance rates among patients with infection. The results were reviewed, and the key factors contributing to noncompliance were identified and addressed. RESULTS: Ninety percent of process measures had lower compliance rates among patients with infection. Detailed review of infection cases identified many defects that improved following the implementation of system-level changes: correct cefotetan redosing (education of anesthesia personnel), temperature at surgical incision >36.0°C (flags used to identify patients for preoperative warming), and the use of preoperative mechanical bowel preparation with oral antibiotics (laxative solutions and antibiotics distributed in clinic before surgery). Quarterly compliance improved for 80% of process measures by the end of the study period. LIMITATIONS: This study was conducted on a small surgical cohort within a select subspecialty. CONCLUSIONS: The infection auditing tool is a useful strategy for identifying defects and guiding quality improvement interventions. This is an iterative process requiring dedicated resources and continuous patient and frontline provider engagement.

Avoiding immortal time bias in the American College of Surgeons National Surgical Quality Improvement Program readmission measure.

Results | The age and sex distribution of the LAGB population analyzed is provided in the Figure. During the 3 years after LAGB, the rate of revisional surgery was 18.9 events per 100 patients, comprising 11.4 intra-abdominal and 7.5 subcutaneous surgical procedures. The majority of revisional procedures were repeated or revisional LAGB procedures (8.3 events per 100 patients) and repairs or revisions of the LAGB reservoir (7.5 events per 100 patients). Conversions to another bariatric procedure (1.3 events per 100 patients) and LAGB reversals (1.9 events per 100 patients) were uncommon (Table).

Medical Harm: Patient Perceptions and Follow-up Actions

Objectives Much research has been conducted to describe medical mistakes resulting in patient harm using databases that capture these events for medical organizations. The objective of this study was to describe patients’ perceptions regarding disclosure and their actions after harm. Methods We analyzed a patient harm survey database composed of responses from a voluntary online survey administered to patients by ProPublica, an independent nonprofit news organization, during a 1-year period (May 2012 to May 2013). We collected data on patient demographics and characteristics related to the acknowledgment of patient harms, the reporting of patient harm to an oversight agency, whether the patient or the family obtained the harm-associated medical records, as well as the presence of a malpractice claim. Results There were 236 respondents reporting a patient harm (mean age, 49.1 y). In 11.4% (27/236) of harms, an apology by the medical organization or the clinician was made. In 42.8% (101/236) of harms, a complaint was filed with an oversight agency. In 66.5% (157/236) of harms, the patient or the family member obtained a copy of the pertinent medical records. A malpractice claim was reported in 19.9% (47/236) of events. Conclusions In this sample of self-reported patient harms, we found a perception of inadequate apology. Nearly half of patient harm events are reported to an oversight agency, and roughly one-fifth result in a malpractice claim.

Ureteral Injury During Laparoscopic Colectomy: The Need for More Information: Comment on “Incidence of Iatrogenic Ureteral Injury After Laparoscopic Colectomy”

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