ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections.

Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not the only, approach to clinical scenarios.

Increased Postoperative Morbidity Associated With Prolonged Laparoscopic Colorectal Resections Is Not Increased by Resident Involvement.

BACKGROUND: Although longer operative times are associated with increased postoperative morbidity, the influence of surgical residents on this association is unclear. OBJECTIVE: The purpose of this study was to evaluate whether morbidity associated with operative times in laparoscopic colorectal surgery is increased by resident training. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted using a national database. PATIENTS: Laparoscopic ileocolectomies, partial colectomies, and low anterior resections were identified in the National Surgical Quality Improvement Project (2005-2012). This cohort was stratified by the presence of resident involvement (postgraduate clinical year ≤5) and then divided into tertiles of operative time (low, medium, and high), allowing comparisons of cases by duration with resident involvement with cases of similar length without resident involvement. MAIN OUTCOME MEASURES: Postoperative morbidity (infectious and noninfectious), length of hospital stay, and unplanned reoperations were the primary study outcomes. RESULTS: A total of 20,785 procedures were identified. In aggregate, prolonged operative time was associated with both infectious (OR = 1.49, p < 0.001 with residents; OR = 1.38, p < 0.001 without residents) and noninfectious complications (OR = 1.51, p < 0.001 with residents; OR = 1.48, p < 0.001 without residents) when compared with short cases without residents. Longer hospital stay was observed both within the highest (additional 1.2 days (p < 0.001) with residents; 1.1 days (p < 0.001) without residents) and middle (additional 0.4 days (p < 0.001) with residents; 0.4 days (p = 0.001) without residents) tertiles of operative time. Within the highest tertile of operative length, there was no statistically significant difference in complication rates between cases with and without resident participation. LIMITATIONS: The study was limited by its retrospective design and inability to define the complexity of case and extent of resident involvement. CONCLUSIONS: Although longer operative times confer increased postoperative morbidity, there was no significant difference in complication rates within the highest tertile between cases with and without resident participation. Resident involvement does not appear to add to the risk of morbidity associated with longer and more complicated surgeries. See Video Abstract at http://links.lww.com/DCR/A440.

Advances in therapeutic bacterial antisense biotechnology.

Antisense therapeutics are a biotechnological form of antibiotic therapy using chemical analogues of short single-stranded nucleic acid sequences modified to form stable oligomers. These molecules are termed antisense oligonucleotides (ASOs) because their sequence is complementary, via Watson-Crick specific base pairing, to their target messenger RNA (mRNA). ASOs modify gene expression in this sequence-dependent manner by binding to its complementary mRNA and inhibiting its translation into protein through steric blockage and/or through RNase degradation of the ASO/RNA duplex. The widespread use of conventional antibiotics has led to the increasing emergence of multiple drug-resistant pathogenic bacteria. There is an urgent need to develop alternative therapeutic strategies to reduce the morbidity and mortality associated with bacterial infections, and until recently, the use of ASOs as therapeutic agents has been essentially limited to eukaryotic cells, with ASOs as antibacterials having been largely unexplored primarily due to the poor uptake efficiency of antisense molecules by bacteria. There are conceptual advantages to bacterial antisense antibiotic therapies, including a sequence-dependent approach that allows for a rational design to multiple specific molecular targets. This review summarizes the current knowledge of antisense bacterial biotechnology and highlights the recent progress and the current obstacles in their development for therapeutic applications.

Adjuvant Chemotherapy Improves Overall Survival of Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy Regardless of Pathologic Nodal Status.

BACKGROUND: After neoadjuvant chemoradiotherapy for rectal cancer, the interpretation of surgical pathology poses difficulties in deciding the need for adjuvant chemotherapy (AC). The aim of this study was to determine whether there is a survival benefit to providing AC in patients with node-negative disease on surgical pathology. METHODS: Patients with clinical stage II and III rectal adenocarcinoma who received neoadjuvant chemoradiation and definitive surgical resection from 2006 to 2012 were identified in the National Cancer Data Base. Patients were stratified by both receipt of AC and nodal status on surgical pathology. Propensity score matching was used to form two cohorts (AC vs. no AC) with otherwise balanced characteristics. Overall survival was compared by Kaplan-Meier analysis, and multivariable survival analysis was performed by a Weibull model. RESULTS: After propensity score matching, 4172 patients who received adjuvant therapy (2645 node negative and 1527 node positive) and 4172 patients who did not receive adjuvant therapy (3063 node negative and 1109 node positive) were identified. Among patients with either node-negative or node-positive disease, the use of AC was associated with a significant improvement in overall survival. These results were also observed after using a multivariable survival model to control for clinical stage as well as patient- and facility-related characteristics. CONCLUSIONS: In both patients with node-negative and node-positive disease on surgical pathology, the use of AC is associated with a survival benefit. In the absence of contraindications, AC should continue to be routinely recommended to patients after neoadjuvant chemoradiotherapy for locally advanced rectal cancers.

Squamous Cancers of the Rectum Demonstrate Poorer Survival and Increased Need for Salvage Surgery Compared With Squamous Cancers of the Anus.

BACKGROUND: Squamous cell cancers of the anus are rare GI malignancies for which neoadjuvant chemoradiation is the first-line treatment for nonmetastatic disease. Squamous cancers of the rectum are far less common, and it is unclear to what degree chemoradiotherapy improves their outcomes. OBJECTIVE: The purpose of this study was to compare stage-specific survival for anal and rectal squamous cancers stratified by treatment approach. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at Commission on Cancer designated hospitals. PATIENTS: Patients (2006-2012) identified in the National Cancer Database with pretreatment clinical stage I to III cancers who underwent chemoradiotherapy, with and without subsequent salvage surgical resection (low anterior resection or abdominoperineal resection), ≥12 weeks after chemoradiotherapy were included in the study. MAIN OUTCOME MEASURES: Overall survival and the need for salvage surgery were measured. RESULTS: Anal cancers (n = 11,224) typically presented with stage II (45.7%) or III (36.3%) disease, whereas rectal cancer stages (n = 1049) were more evenly distributed (p < 0.001). More patients with rectal cancer underwent low anterior or abdominoperineal resections 12 weeks or later after chemoradiotherapy versus those undergoing abdominoperineal resection for anal cancer (3.8% versus 1.2%; p < 0.001). Stage I and II rectal cancer was associated with poorer survival compared with anal cancer (stage I, p = 0.017; stage II, p < 0.001); survival was similar for stage III disease. Salvage surgery for anal cancer was associated with worse survival for stage I to III cancers; salvage surgery did not significantly affect survival for rectal cancer. LIMITATIONS: This was a retrospective study without cancer-specific survival measures. CONCLUSIONS: Squamous rectal cancers are associated with significantly worse survival than squamous cancers of the anus for clinical stage I and II disease. Despite both cancers exhibiting squamous histology, rectal cancers may be less radiosensitive than anal cancers, as suggested by the greater incidence of salvage surgery that does not appear to significantly improve overall survival. See Video Abstract at http://links.lww.com/DCR/A422.

A Surgical Clostridium-Associated Risk of Death Score Predicts Mortality After Colectomy for Clostridium difficile.

BACKGROUND: A Clostridium difficile-associated risk of death score was recently developed and validated by using a national cohort of both nonsurgical and surgical patients admitted with C difficile infection. However, risk scores specifically derived from surgical cohorts and designed for patients with C difficile infection are currently unavailable. OBJECTIVE: The aim of this study was to develop a risk of death score for patients with C difficile infection who are being considered for total abdominal colectomy because of the failure of medical therapy. DESIGN: This is a retrospective cohort study. SETTINGS: This study was conducted with the use of a national database. PATIENTS: All patients undergoing total colectomy for C difficile infection were identified in the National Surgical Quality Improvement Program database from 2005 to 2014. MAIN OUTCOME MEASURES: Variables similar to the original scoring system were used in multivariable analyses to determine the risk of 30-day mortality for patients, and a model was constructed to estimate the predicted probability of mortality after surgery. RESULTS: Of 532 patients who underwent surgery, 32.7% experienced 30-day postoperative mortality. Patient covariates associated with significantly increased mortality included age greater than 80 years (OR 5.5, p = 0.003), need for preoperative mechanical ventilation (OR 3.1, p < 0.001), chronic steroid use (OR 2.9, p < 0.001), underlying cardiopulmonary disease (OR 2.0, p = 0.001), and acute renal failure (OR=1.7, p = 0.03). These and other comorbidities, including hepatic disease, a cancer diagnosis, and both insulin- and noninsulin-dependent diabetes mellitus, were used to construct a model to estimate the predicted probability of mortality, which ranged from 8.0% to 96.1% based on individual comorbidity profiles. These estimates differed substantially when compared with those obtained using the National Surgical Quality Improvement Program risk calculator, which estimated the risk of mortality among surgical patients as being consistently lower. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: Our surgical scoring system allows preoperative risk stratification for patients being evaluated for colectomy for C difficile infection, potentially helping to avoid futile surgery. See Video Abstract at http://links.lww.com/DCR/A434.

Palliative therapy for stage IV rectal adenocarcinoma: how frequently is it used?

BACKGROUND: Palliative care is associated with decreased cost and improved quality of life, although its use in stage IV rectal cancer is understudied. MATERIALS AND METHODS: Stage IV rectal cancer patients (2004-2011) who did not undergo surgery with curative intent were identified within the National Cancer Database. Patients receiving palliative therapy were stratified by the type of intervention, as were patients undergoing chemotherapy that was not designated as palliative. Logistic regression was used to identify factors associated with the receipt of palliative therapy. RESULTS: A total of 11,245 patients were analyzed, of which 2314 (20.6%) received palliative therapy. Use of palliative therapy as a category of treatments did not change significantly from 2004-2012 (19.4%-23.0%; P = 0.14), but the use of palliative chemotherapy nearly doubled (4.7%-8.7%; P < 0.001). Factors associated with the use of palliative therapy included age >60 y and increasing chronic comorbidities; these subgroups also had lower odds of receiving chemotherapy that was not designated as palliative. Differences in gender and race were not associated with variations in the receipt of palliative therapy. CONCLUSIONS: For stage IV rectal cancers managed without curative intent, use of palliative therapies remains consistently low, with a preference for sicker patients.

Inpatient infliximab is ineffective at preventing colectomy for steroid refractory extensive colitis.

BACKGROUND: Despite data suggesting safety and efficacy in ulcerative colitis patients treated with inpatient infliximab, prior studies did not focus on patients with extensive colitis, the group at highest risk for requiring surgery. METHODS: This was a single center, retrospective study (2008-2015) of consecutive patients who required admission because of severe extensive ulcerative colitis defined by preoperative symptoms and computed tomography scans and postoperative histology. Patients admitted for high-dose steroids were compared with steroid refractory inpatients provided with one or two infusions of infliximab. The primary study outcome was colectomy rates; secondary outcomes included mean length of stay and 60-d complication rates. RESULTS: A total of 174 patients required admission with steroids for extensive ulcerative colitis. Of these, 19 (10%) also received infliximab. Among the subjects treated with infliximab, 15 (78%) required total colectomy during that admission versus 81 (52%) who received steroids alone (P = 0.03). Postoperative readmission rates, surgical-site infections, return to the operating room, and all-complication rates were similar between the cohorts (P > 0.05). CONCLUSIONS: For steroid refractory extensive ulcerative colitis, inpatient infliximab did not lower colectomy rates or increase postoperative complications compared with patients treated with steroids alone.

Clostridium difficile Infection Is Associated With Lower Inpatient Mortality When Managed by GI Surgeons.

BACKGROUND: Patients admitted with Clostridium difficile infection are managed in a variety of settings. If their care is inadequate, these patients can rapidly deteriorate. OBJECTIVE: The purpose of this study was to evaluate whether mortality for patients admitted with C difficile differed between medical and general/colorectal surgery services. DESIGN: This was a retrospective cohort study with multivariable logistic regression used to evaluate the effect of admitting service on in-hospital mortality rates, with propensity score matching used to validate this relationship. SETTINGS: The study was conducted at a single, tertiary care center. PATIENTS: Inpatients with a positive C difficile stool test within 24 hours of admission to medical or surgical services were identified (2005-2015) using institutional electronic data sources. MAIN OUTCOME MEASURE: We measured inpatient mortality rate. RESULTS: Of 1175 patients, 985 (83%) were admitted to medical services, whereas 190 (17%) were admitted by surgeons. Medical patients were older (63.9 vs 58.9 years; p = 0.001) and had a mean of 0.6 additional comorbidities (p < 0.001); cohorts were similar regarding vasopressors, peak white blood cell counts, and rate of intensive care unit admissions. Mortality was lower among surgery patients (2.6% vs 6.8%; p = 0.028), and logistic regression demonstrated lower odds of mortality for this group OR = 0.18 (95% CI, 0.05-0.58)). After propensity score matching for age, comorbidities, and severity of disease, this difference was confirmed (2.6% vs. 9.5%). A higher incidence of total colectomy for surgery patients (14.2% vs 0.4%) was a causal factor in their longer lengths of stay and higher total hospital costs. The time between orders for stool testing and metronidazole therapy was shorter in the surgery group (1.8 vs 3.8 hours; p = 0.002), although this trend was not observed with vancomycin therapy. LIMITATIONS: This was a retrospective study from a single institution, thereby limiting generalizability, with a lack of information regarding premorbid creatinine levels, ileus, or megacolon. CONCLUSIONS: In-hospital mortality rates for patients admitted with C difficile were lower on surgery services, perhaps in part related to higher colectomy rates.

Single-Site Laparoscopic Colorectal Surgery Provides Similar Clinical Outcomes Compared With Standard Laparoscopic Surgery: An Analysis of 626 Patients.

BACKGROUND: Compared with standard laparoscopy, single-site laparoscopic colorectal surgery may potentially offer advantages by creating fewer surgical incisions and providing a multifunctional trocar. Previous comparisons, however, have been limited by small sample sizes and selection bias. OBJECTIVE: The purpose of this study was to compare 60-day outcomes between standard laparoscopic and single-site laparoscopic colorectal surgery patients undergoing elective and urgent surgeries. DESIGN: This was an unselected, retrospective cohort study comparing patients who underwent elective and unplanned standard laparoscopic or single-site laparoscopic colorectal resections for benign and malignant disease between 2008 and 2014. Outcomes were compared using univariate analyses. SETTINGS: This study was conducted at a single institution. PATIENTS: A total of 626 consecutive patients undergoing laparoscopic colorectal surgery were included. MAIN OUTCOME MEASURES: Morbidity and mortality rates within 60 postoperative days were measured. RESULTS: A total of 318 (51%) and 308 patients (49%) underwent standard laparoscopic and single-site laparoscopic procedures. No significant differences were noted in mean operative time (standard laparoscopy, 182.1 ± 81.3 vs single-site laparoscopy, 177.0 ± 86.5; p = 0.30) or postoperative length of stay (standard laparoscopy, 4.8 ± 3.4 vs single-site laparoscopy, 5.5 ± 6.9; p = 0.14). Conversions to laparotomy and 60-day readmissions were also similar for both cohorts across all of the procedures performed. A significant difference was identified in the number of patients who developed postoperative complications (standard laparoscopy, 19.2% vs single-site laparoscopy, 10.7%; p = 0.004), especially with respect to surgical-site infections (standard laparoscopy, 11.3% vs single-site laparoscopy, 5.8%; p = 0.02). LIMITATIONS: This was a retrospective, single institution study. CONCLUSIONS: Single-site laparoscopic colorectal surgery demonstrates similar results to standard laparoscopic colorectal surgery with regard to operative time, length of stay, and readmissions. Single-site laparoscopic colorectal surgery may provide advantages in limiting the development of certain complications, such as superficial surgical-site infections.

Prospective multicenter study of a synthetic bioabsorbable anal fistula plug to treat cryptoglandular transsphincteric anal fistulas.

BACKGROUND: Although interest in sphincter-sparing treatments for anal fistulas is increasing, few large prospective studies of these approaches have been conducted. OBJECTIVE: The study assessed outcomes after implantation of a synthetic bioabsorbable anal fistula plug. DESIGN: A prospective, multicenter investigation was performed. SETTING: The study was conducted at 11 colon and rectal centers. PATIENTS: Ninety-three patients (71 men; mean age, 47 years) with complex cryptoglandular transsphincteric anal fistulas were enrolled. Exclusion criteria included Crohn's disease, an active infection, a multitract fistula, and an immunocompromised status. INTERVENTION: Draining setons were used at the surgeon's discretion. Patients had follow-up evaluations at 1, 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES: The primary end point was healing of the fistula, defined as drainage cessation plus closure of the external opening, at 6 and 12 months. Secondary end points were fecal continence, duration of drainage from the fistula, pain, and adverse events during follow-up. RESULTS: Thirteen patients were lost to follow-up and 21 were withdrawn, primarily to undergo an alternative treatment. The fistula healing rates at 6 and 12 months were 41% (95% CI, 30%-52%; total n = 74) and 49% (95% CI, 38%-61%; total n = 73). Half the patients in whom a previous treatment failed had healing. By 6 months, the mean Wexner score had improved significantly (p = 0.0003). By 12 months, 93% of patients had no or minimal pain. Adverse events included 11 infections/abscesses, 2 new fistulas, and 8 total and 5 partial plug extrusions. The fistula healed in 3 patients with a partial extrusion. LIMITATIONS: The study was nonrandomized and had relatively high rates of loss to follow-up. CONCLUSION: Implantation of a synthetic bioabsorbable fistula plug is a reasonably efficacious treatment for complex transsphincteric anal fistulas, especially given the simplicity and low morbidity of the procedure.

Determinants of 30-d readmission after colectomy.

BACKGROUND: Readmission after colectomy has become an important metric for measuring quality of care. Our aim was to investigate the impact of patient and hospital characteristics on 30-d readmission rates among patients undergoing colectomies in Pennsylvania. METHODS: Data were obtained from the Pennsylvania Health Care Cost Containment Council, which included all patients undergoing colectomy during 2011 (n = 10,155). Characteristics of non-readmitted and readmitted patients were compared with univariate tests. The primary outcome was 30-d readmission, which was modeled using multivariable logistic regression. RESULTS: Of the 10,155 patients who underwent colectomy, 1492 (14.7%) were readmitted within 30 d of discharge. Readmission was influenced by the underlying diagnosis (P < 0.001). Additionally, readmission was more likely with a Charlson comorbidity index ≥ 2 (odds ratio [OR] = 1.57, P < 0.001), emergent admission (OR = 1.26, P = 0.001), an in-hospital complication (OR = 1.46, P < 0.001), lowest quartile for surgeon volume (OR = 1.24, P = 0.01), and construction of an ileostomy (OR = 2.31, P < 0.001). Factors associated with decreased likelihood of readmission included laparoscopic surgery (OR = 0.73, P < 0.001). No association with hospital volume was found. CONCLUSIONS: A 30-d readmission after colectomy is influenced by numerous patient- and surgeon-related factors. Reducing in-hospital complications, and improving patient education after ileostomy construction, provide substantial targets for intervention. Our data also suggest that there may be a critical range of colectomies performed annually by surgeons, greater than which no additional benefit is conferred in reducing readmissions, but below which there is an increased risk of readmission. Further research is needed to determine the influence of laparoscopic surgery in reducing readmission in equally matched patient populations.

Single nucleotide polymorphisms of the tcdC gene and presence of the binary toxin gene predict recurrent episodes of Clostridium difficile infection.

OBJECTIVE: To identify Clostridium difficile genotypes, which are associated with recurrent C difficile infection (RCDI). BACKGROUND: Reliable bacterial genetic factors predicting RCDI are currently lacking. METHODS: Inpatients and outpatients 18 years or older treated at our institution for C difficile infection (CDI) of any severity were consecutively enrolled. CDI was defined as symptoms of colitis with a positive PCR stool test. Each bacterial isolate was studied for virulence factors: tcdC mutations, including single nucleotide polymorphisms (SNPs) via PCR, the presence of genes for toxins A, B and binary toxin using restriction fragment length polymorphism, and identification of ribotype by PCR. χ tests, t tests, and logistic and linear regression were used to determine which virulence factors predicted RCDI and the need for hospital admission, with corrections made for multiple statistical comparisons. RESULTS: Seventy-three patients (male: 52%; mean age: 66 ± 15 years) were studied. Binary toxin gene (P = 0.03) was associated with at least 1 episode of RCDI, as was the presence of SNPs C184T (P = 0.006) and A117T (P = 0.003). The presence of the binary toxin gene with either of these tcdC SNPs increased RCDI by 80% (P = 0.0002) but did not predict the need for hospital admission. None of the other virulence factors, including ribotype 027, were predictive of RCDI. CONCLUSIONS: The presence of the binary toxin gene and tcdC SNPs C184T and A117T strongly predict RCDI. The presence of both tcdC SNPs and the binary toxin gene significantly increased the risk of RCDI, which might warrant longer antibiotic courses to eradicate the infection.

How do risk factors for mortality and overall complication rates following laparoscopic and open colectomy differ between inpatient and post-discharge phases of care? A retrospective cohort study from NSQIP.

BACKGROUND: Risk factors for complications differ between laparoscopic (LC) and open colectomy (OC) patients, given the selection bias between these groups. How risk factors for these outcomes differ between inpatient and post-discharge phases of care requires further study. METHODS: A retrospective cohort study (2005-2010) using NSQIP data was performed comparing OC and LC patients. Multivariable logistic regression was used to compare covariates associated with mortality and overall complication rates both before and after hospital discharge. RESULTS: Patients in the LC cohort were younger (64.2 vs. 62.5 years; P < 0.0001) with a lower incidence of comorbidities. OC was associated with a higher incidence of mortality compared to LC among inpatients (3.3 vs. 0.61%, P < 0.0001) and following discharge (0.88 vs. 0.29%, P < 0.0001). OC also demonstrated a higher incidence of overall complication rates for both inpatients (22.32 vs. 9.36%, P < 0.0001) and following discharge (8.83 vs. 7.24%, P < 0.0001). Risk factors (P < 0.05) for mortality following LC included age and emergency procedures for inpatients; pre-operative SIRS was associated with mortality occurring after discharge. For the OC cohort, risk for mortality was increased with smoking and contaminated/dirty wounds for inpatients; pre-operative weight loss was associated with death following discharge. Factors associated with increased risk of morbidity following LC included smoking history for inpatients and pre-operative steroid therapy following discharge. Following OC, morbidity was strongly associated with ASA scores for inpatients; pre-operative steroid therapy was a risk factor following discharge. Obesity was strongly associated with non-mortal complications in both cohorts following discharge. CONCLUSIONS: (1) LC is associated with a lower incidence of post-operative mortality and complications. (2) Risk factors associated with adverse post-operative outcomes change during the post-operative period; surveillance for these outcomes should be tailored by operative technique and phase of post-operative care (3) Obesity is an underappreciated risk for complications following discharge for both LC and OC.