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.
We examined the immune microenvironment of primary colorectal cancer using immunohistochemistry, laser capture microdissection/qRT-PCR, flow cytometry, and functional analysis of tumor-infiltrating ...lymphocytes. A subset of colorectal cancer displayed high infiltration with activated CD8(+) cytotoxic T lymphocyte (CTL) as well as activated Th1 cells characterized by IFNγ production and the Th1 transcription factor TBET. Parallel analysis of tumor genotypes revealed that virtually all of the tumors with this active Th1/CTL microenvironment had defects in mismatch repair, as evidenced by microsatellite instability (MSI). Counterbalancing this active Th1/CTL microenvironment, MSI tumors selectively demonstrated highly upregulated expression of multiple immune checkpoints, including five-PD-1, PD-L1, CTLA-4, LAG-3, and IDO-currently being targeted clinically with inhibitors. These findings link tumor genotype with the immune microenvironment, and explain why MSI tumors are not naturally eliminated despite a hostile Th1/CTL microenvironment. They further suggest that blockade of specific checkpoints may be selectively efficacious in the MSI subset of colorectal cancer.
The findings reported in this article are the first to demonstrate a link between a genetically defined subtype of cancer and its corresponding expression of immune checkpoints in the tumor microenvironment. The mismatch repair-defective subset of colorectal cancer selectively upregulates at least five checkpoint molecules that are targets of inhibitors currently being clinically tested.
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 N1, N12-diacetylspermine in both biofilm-positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N1, N12-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.
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•Colonic mucosal biofilms alter the cancer metabolome•N1, N12-diacetylspermine was significantly upregulated in tissues with biofilms•Biofilms create conditions conducive to oncogenic transformation in colon cells•Global isotope metabolomics reveals the metabolite fate of N1, N12-diacetylspermine
Johnson et al. examine the metabolomics of bacterial communities called biofilms and human colon cancers. The host and bacterial polyamine metabolites are proposed to act together to promote biofilm formation and cancer growth, creating conditions conducive for normal to cancer cell transformation.
Hospital Readmission by Method of Data Collection Hechenbleikner, Elizabeth M., MD; Makary, Martin A., MD, MPH, FACS; Samarov, Daniel V., PhD ...
Journal of the American College of Surgeons,
06/2013, Letnik:
216, Številka:
6
Journal Article
Recenzirano
Background Hospital readmissions are increasingly used to pay hospitals differently. We hypothesized that readmission rates, readmissions related to index admission, and potentially unnecessary ...readmissions vary by data collection method for surgical patients. Study Design Using 3 different data collection methods, we compared 30-day unplanned readmission rates and potentially unnecessary readmissions among colorectal surgery patients at a single institution between July 2009 and November 2011. We compared the NSQIP clinical reviewer method, the University HealthSystem Consortium (UHC) administrative billing data method, and physician medical record review. Results Seven hundred and thirty-five colorectal surgery patients were identified with readmission rates as follows: NSQIP 14.6% (107 of 735) vs UHC 17.6% (129 of 735). The NSQIP method identified 9 readmissions not found in billing records because the readmission occurred at another hospital (n = 7) or due to a discrepancy in definition (n = 2). The UHC method identified 31 readmissions not identified by NSQIP because of a broader readmission definition (n = 20) or were missed by reviewers (n = 11). The NSQIP method identified 72% of readmissions as related to index admission and physician chart review identified 83%. The UHC method identified 51% of readmissions as related to index admission and physician chart review identified 86%. Sixty-six of 129 UHC readmissions (51%) were deemed potentially preventable; based on physician chart review, 112 of 129 readmissions (87%) were deemed clinically necessary at the time of presentation. Most readmissions were due to surgical site infections (46 of 129 36%) and dehydration (30 of 129 23%). With improved patient-care efforts, 41 of 129 (31.8%) complications might not have required readmission. Conclusions Readmission rates and unnecessary readmissions vary depending on data collection methodology. Reimbursements based on readmission should use standardized and fair methods to minimize perverse incentives that penalize hospitals for appropriate care of high-risk surgical patients.
Background Minority-serving hospitals have greater readmission rates after operative procedures including colectomy; however, little is known about the contribution of hospital factors to readmission ...risk and mortality in this setting. This study evaluated the impact of hospital factors on readmissions and inpatient mortality after colorectal resections at minority-serving hospitals in the context of patient- and procedure-related factors. Methods More than 168,000 patients who underwent colorectal resections in 374 California hospitals (2004–2011) were analyzed using the State Inpatient Database and American Hospital Association Hospital Survey data. Sequential logistic regression analyses were performed to determine the associations between minority-serving hospital status and 30-day, 90-day, and repeated readmissions. Results Thirty-day, 90-day, and repeated readmission rates were 11.2%, 16.9%, and 2.9%, respectively. Odds for 30-day, 90-day, and repeated readmissions after colorectal resections were 19%, 20%, and 38% more likely at minority-serving hospitals versus non-minority-serving hospitals, respectively ( P < .01), after controlling for age, sex, comorbidities, year, and procedure type. Patient factors accounted for up to 65% of the observed increase in odds for readmission at minority-serving hospitals while hospital-level factors contributed roughly 40%. Inpatient mortality was significantly greater at minority-serving hospitals versus non-minority-serving hospitals (4.9% vs 3.8%; P < .001). Risk factors significantly associated with readmissions and inpatient mortality included Medicaid/Medicare primary insurance, emergent operation, and ostomy creation. Low procedure volume was significantly associated with increased odds for inpatient mortality. Conclusion Patient-level factors seemed to dominate the increased readmission risk after colorectal resections at minority-serving hospitals while hospital factors were less contributory. These findings need to be further validated to shape quality improvement interventions to decrease readmissions.
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
and
Genes for colibactin (
) and
toxin (
), encoding secreted oncotoxins, were highly enriched in FAP patients' colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with
(expressing colibactin), and enterotoxigenic
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.
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.
We sought to qualitatively analyze studies describing surgical techniques and outcomes in adult acquired rectourethral fistulas to outline universal approaches for evaluation and management.
MEDLINE (PubMed, Ovid) and the Cochrane Library were searched by using the terms rectourethral fistulas, recto-urethral fistulas, urethrorectal fistulas, and prostatourethral-rectal fistulas.
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.
The intervention was surgical repair of rectourethral fistula.
The main outcome measures were successful fistula closure, fistula recurrence or persistence, and permanent fecal and/or urinary diversion.
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.
This review was limited by the heterogeneity of repairs and bias toward preferred surgical approaches in single-center studies.
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 undergoing sleeve gastrectomy (SG) experience transformative changes in eating-related experiences that include eating-related symptoms, emotions, and habits. Long-term assessment of these ...endpoints with rigorous patient-reported outcome measures (PROMs) is limited. We assessed patients undergoing SG with the Body-Q Eating Module PROMs.BACKGROUNDPatients undergoing sleeve gastrectomy (SG) experience transformative changes in eating-related experiences that include eating-related symptoms, emotions, and habits. Long-term assessment of these endpoints with rigorous patient-reported outcome measures (PROMs) is limited. We assessed patients undergoing SG with the Body-Q Eating Module PROMs.All patients evaluated at the Emory Bariatric Center were given the Body-Q Eating Modules questionnaire at preoperative/postoperative clinic visits. Rasch scores and prevalence of relevant endpoints were assessed across six time-points of interest: preoperatively, post-operative months 0-6, 7-12, 12-24, 24-36, and over 36. Student's t-test and Chi-square test were used for analysis.METHODSAll patients evaluated at the Emory Bariatric Center were given the Body-Q Eating Modules questionnaire at preoperative/postoperative clinic visits. Rasch scores and prevalence of relevant endpoints were assessed across six time-points of interest: preoperatively, post-operative months 0-6, 7-12, 12-24, 24-36, and over 36. Student's t-test and Chi-square test were used for analysis.Overall, 1,352 questionnaires were completed pre-operatively and 493 postoperatively. Survey compliance was 81%. Compared to the pre-operative group, the post-operative group had lower BMI (39.7 vs. 46.4, p < 0.001) and higher age (46.3 vs. 44.9, p = 0.019). Beginning one year after SG, patients experience more frequent eating-related pain, nausea and constipation compared to pre-operative baseline (p < 0.05). They also more frequently experience eating-related regurgitation and dumping syndrome-related symptoms beginning post-operative year two (p < 0.05). In the first year after SG, patients more rarely feel eating-related embarrassment, guilt, and disappointment compared to pre-operative baseline (p < 0.05). These improvements disappear one year after SG, after which patients more frequently experience feeling out of control, unhappy, like a failure, disappointed, and guilty (p < 0.05). In the first year after SG, patients experience an increased frequency in positive eating behaviors (ate healthy foods, showed self-control, stopped before full; (p < 0.05). Only two eating-related behavior improvements persist long-term: feeling in control and eating the right amount (p < 0.05).RESULTSOverall, 1,352 questionnaires were completed pre-operatively and 493 postoperatively. Survey compliance was 81%. Compared to the pre-operative group, the post-operative group had lower BMI (39.7 vs. 46.4, p < 0.001) and higher age (46.3 vs. 44.9, p = 0.019). Beginning one year after SG, patients experience more frequent eating-related pain, nausea and constipation compared to pre-operative baseline (p < 0.05). They also more frequently experience eating-related regurgitation and dumping syndrome-related symptoms beginning post-operative year two (p < 0.05). In the first year after SG, patients more rarely feel eating-related embarrassment, guilt, and disappointment compared to pre-operative baseline (p < 0.05). These improvements disappear one year after SG, after which patients more frequently experience feeling out of control, unhappy, like a failure, disappointed, and guilty (p < 0.05). In the first year after SG, patients experience an increased frequency in positive eating behaviors (ate healthy foods, showed self-control, stopped before full; (p < 0.05). Only two eating-related behavior improvements persist long-term: feeling in control and eating the right amount (p < 0.05).Patients undergoing SG may experience more frequent eating-related symptoms, distress, and behavior in the long-term. These findings can enhance the pre-operative informed consent and guide development of a more tailored approach to postoperative clinical management such as more frequent visits with the dietician.CONCLUSIONSPatients undergoing SG may experience more frequent eating-related symptoms, distress, and behavior in the long-term. These findings can enhance the pre-operative informed consent and guide development of a more tailored approach to postoperative clinical management such as more frequent visits with the dietician.
Intraoperative radiation therapy (IORT) is a minimally invasive radiation option for select patients with early stage breast cancer. This prospective, single institution, pilot study summarizes ...patient-reported quality of life (QoL) outcomes and clinician-reported toxicity following IORT following breast conservation therapy.
Forty-nine patients were enrolled in a prospective study from 2013 until 2015 to assess QoL and toxicity following breast conservation therapy and IORT. Nine patients did not meet criteria for IORT alone on final pathology and required whole breast irradiation afterwards. These patients were evaluated separately. Validated QoL questionnaires were provided to patients at 1-week, 1-month, and subsequent 6-month intervals for 2 years. Radiation-related toxicity symptoms were evaluated by clinicians at the same time intervals. Likert scale responses were converted to continuous variables to depict patient-reported and clinician-reported outcomes.
Outcomes were analyzed as weighted averages of the Likert scale for each symptom. Responses for negative QoL symptoms ranged largely from 0 (none) to 2 (moderate). Responses for positive QoL symptoms ranged largely from 3 (quite a bit) to 4 (very much). Seventy-five percent of patients developed a toxicity; however, 99% of the toxicities were grades 1 and 2. All toxicities demonstrated a downward trend over time, with the exception of breast fibrosis and nodularity, which increased over time. There were no local recurrences upon 2-year follow up.
Early stage breast cancer treated with IORT yields favorable QoL outcomes and minimal toxicity profiles with adequate short-term local control.
Assessment of surgical resident technical performance is an integral component of any surgical training program. Timely assessment delivered in a structured format is a critical step to enhance ...technical skills, but residents often report that the quality and quantity of timely feedback received is lacking. Moreover, the absence of written feedback with specificity can allow residents to seemingly progress in their operative milestones as a junior resident, but struggle as they progress into their postgraduate year 3 and above. We therefore designed and implemented a web-based intraoperative assessment tool and corresponding summary "dashboard" to facilitate real-time assessment and documentation of technical performance.
A web form was designed leveraging a cloud computing platform and implementing a modified Ottawa Surgical Competency Operating Room Evaluation instrument; this included additional, procedure-specific criteria for select operations. A link to this was provided to residents via email and to all surgical faculty as a Quick Response code. Residents open and complete a portion of the form on a smartphone, then relinquish the device to an attending surgeon who then completes and submits the assessment. The data are then transferred to a secure web-based reporting interface; each resident (together with a faculty advisor) can then access and review all completed assessments.
The Assessment form was activated in June 2021 and formally introduced to all residents in July 2021, with residents required to complete at least one assessment per month. Residents with less predictable access to operative procedures (night float or Intensive Care Unit) were exempted from the requirement on those months. To date a total of 559 assessments have been completed for operations performed by 56 trainees, supervised by 122 surgical faculty and senior trainees. The mean number of procedures assessed per resident was 10.0 and the mean number per assessor was 4.6. Resident initiation of Intraoperative Assessments has increased since the tool was introduced and scores for technical and nontechnical performance reliably differentiate residents by seniority.
This novel system demonstrates that an online, resident-initiated technical assessment tool is feasible to implement and scale. This model's requirement that the attending enter performance ratings into the trainee's electronic device ensures that feedback is delivered directly to the trainee. Whether this aspect of our assessment ensures more direct and specific (and therefore potentially actionable) feedback is a focus for future study. Our use of commercial cloud computing services should permit cost-effective adoption of similar systems at other training programs.
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