Characteristics of pathologic complete response for locally advanced rectal cancer.

BACKGROUND: Neoadjuvant chemoradiation (NACRT) is the standard of care for locally advanced rectal cancers. The purpose of this study was to determine patient and tumor factors associated with a pathologic complete response (pCR). METHODS: The National Surgical Quality Improvement Program proctectomy-targeted database was utilized to identify all patients from 2016 to 2020 who underwent NACRT followed by proctectomy with curative intent for T3-4N0-2 rectal cancers. RESULTS: A total of 1891 patients were included, of which 253 (13.4%) demonstrated a pCR. Pretreatment N0 staging was associated with a higher rate of pCR (18.9%) when compared to N1 (6.7%) and N2 (6.7%) (p < 0.0001). Patients clinically staged at T3N0 had the highest rate of pCR (19.5%). Gender, age, race, weight, smoking status, and tumor height were not associated with pCR. CONCLUSIONS: Patients with cN0 disease were more likely to experience a pCR compared to cN1-2 patients. Tumor height relative to anal verge or patient demographics were not associated with pCR.

Evidence-based Prevention of Surgical Site Infection.

Surgical site infection (SSI) remains an important complication of surgery. SSI is estimated to affect 2% to 5% of all surgical patients. Local and national efforts have resulted in significant improvements in the incidence of SSI. Familiarity with evidence surrounding high-quality SSI-reduction strategies is desirable. There exists strong evidence for mechanical and oral antibiotic bowel preparation in colorectal surgery, smoking cessation before elective surgery, prophylactic antibiotics, chlorhexidine-based skin antisepsis, and maintenance of normothermia throughout the perioperative period to reduce SSI. Use of other practices should be determined by the operating surgeon and/or local hospital policy.

Opioid Prescribing Patterns After Anorectal Surgery.

BACKGROUND: Anorectal procedures are frequently performed and have the potential to be particularly painful. There are no evidence-based guidelines regarding opioid prescribing after anorectal surgery and limited data on how surgeons determine opioid prescriptions after anorectal procedures. We hypothesize significant variations in prescribing practices. The aim of this study is to determine current opioid prescribing patterns after anorectal surgery. METHODS: A survey was sent to members of the American Society of Colon and Rectal Surgeons. It included demographics, opioid prescribing habits after anorectal procedures, and factors influencing prescribing. Median morphine equivalents were calculated. Respondents prescribing higher than the median for >4 procedures were considered high prescribers. RESULTS: 519 surveys were completed (3160 sent). 38.6% of respondents were high prescribers, and 61.4% were low prescribers. There were significant differences by years in practice (P = 0.049), hospital type (P = 0.037), region (P < 0.001), and procedures performed per month (P < 0.001). 73% prescribed a standard quantity of opioids for each procedure. The mean milligrams of ME prescribed overall was 129 (SD 82); by procedure the quantities were as follows: hemorrhoidectomy 188 (111), condyloma treatment 149 (105), fistulotomy 146 (98), advancement flap 144 (97), LIFT 140 (93), abscess drainage 107 (91), sphincterotomy 105 (85), chemodenervation 64 (34). Nearly, all (98%) surgeons used local anesthesia. 91% typically prescribed adjunctive medications. In multivariable analysis, performing <10 anorectal procedures per month or practicing in the Northeast or outside the US was associated with low prescribers. High prescribers were more likely to be in practice for >10 y, report >25% of patients request refills, or significantly consider patient satisfaction or phone calls when prescribing. CONCLUSIONS: Opioid prescribing patterns are highly variable after anorectal procedures. Creating opioid prescribing guidelines for anorectal surgery is important to improve patient safety and quality of care.

Ileal Pouch Complications.

Complications after ileal pouch surgery can result in poor pouch function and can have a significant negative impact on a patient's quality of life. Timely diagnosis and appropriate management of complications allows for the best chance of pouch salvage. Many complications require a multimodal approach. As with any reoperative surgery, the success of surgical revision or redo of an ileal pouch is highly dependent on the skill, judgment, and experience of the surgeon and requires an extremely motivated patient.

Reoperative Surgery in Complex Crohn's Disease.

This article provides a structured approach to the technical aspects of reoperative surgery for Crohn's disease. Specific indications for surgery including repeat ileocolic resection, Crohn's complications of ileal pouch anal anastomosis and continent ileostomy, completion proctectomy, and the role of small bowel transplant will be discussed.

Prolonged non-operative management of clostridium difficile colitis is associated with increased mortality, complications, and cost.

BACKGROUND: We aim to investigate the effects of delaying surgery on outcomes and cost in patients admitted with severe clostridium difficile infection (CDI). METHODS: The Vizient database was queried for patients with CDI who underwent open total abdominal colectomy (TAC). Patients operated on the day of admission were excluded. Chi-square, Fisher's exact, student T-test, and logistic regression were performed with α = 0.05. RESULTS: Logistic regression analyses using days from admission to surgery (DATO), age, race, and gender demonstrated that increased DATO was associated with higher 30-day mortality (OR 1.022, 95% CI 1.001-1.044, p = 0.040), overall complications (OR 1.034, 95% CI 1.014-1.054, p = 0.001), and infectious complications (OR 1.040, 95% CI 1.018-1.062, p < 0.001) compared to age for all three outcomes. Total length of stay (LOS), intensive care unit LOS, and direct cost increased in conjunction with DATO (p < 0.001). CONCLUSIONS: Early surgical intervention in appropriately selected patients should be considered when there is a high suspicion for prolonged non-operative treatment.

No survival advantage exists for patients undergoing loop ileostomy for clostridium difficile colitis.

BACKGROUND: We aim to compare outcomes between loop ileostomy (LI) and total abdominal colectomy (TAC) for clostridium difficile infection (CDI) and hypothesize that LI is associated with fewer complications. METHODS: The 2011-2016 ACS-NSQIP database was queried for patients undergoing LI or TAC for CDI. Patients with high outlying age, LOS, and operative time were excluded. Statistics were performed using IBM-SPSS and NCSS PASS-11. RESULTS: Of 457 patients identified, 47 underwent LI. Predicted morbidity was higher in the TAC cohort (62% vs. 37%, p < 0.001). Patients in the LI cohort experienced fewer complications (72% vs. 87%, p = 0.021); however, mortality did not differ between LI (36%) and TAC (31%). Blood transfusions were more than twice as frequent in the TAC cohort (54% vs. 19%, p < 0.001). Four patients in the LI cohort required reoperation; however, none required colectomy. CONCLUSIONS: No mortality difference was observed between LI and TAC. Prospective studies are required to determine the utility of LI. SUMMARY: An analysis of the ACS-NSQIP database was performed and demonstrates that no survival benefit exists for patients who undergo loop ileostomy for C difficile infection compared to those who undergo total colectomy; however, patients who undergo loop ileostomy are likely to retain their colon with low risk of requiring subsequent colectomy.

Application of a simple, affordable quality metric tool to colorectal, upper gastrointestinal, hernia, and hepatobiliary surgery patients: the HARM score.

BACKGROUND: Quality is the major driver for both clinical and financial assessment. There remains a need for simple, affordable, quality metric tools to evaluate patient outcomes, which led us to develop the HospitAl length of stay, Readmission and Mortality (HARM) score. We hypothesized that the HARM score would be a reliable tool to assess patient outcomes across various surgical specialties. METHODS: From 2011 to 2015, we identified colorectal, hepatobiliary, upper gastrointestinal, and hernia surgery admissions using the Vizient Clinical Database. Individual and hospital HARM scores were calculated from length of stay, 30-day readmission, and mortality rates. We evaluated the correlation of HARM scores with complication rates using the Clavien-Dindo classification. RESULTS: We identified 525,083 surgical patients: 206,981 colorectal, 164,691 hepatobiliary, 97,157 hernia, and 56,254 upper gastrointestinal. Overall, 53.8% of patients were admitted electively with a mean HARM score of 2.24; 46.2% were admitted emergently with a mean HARM score of 1.45 (p < 0.0001). All HARM components correlated with patient complications on logistic regression (p < 0.0001). The mean length of stay increased from 3.2 ± 1.8 days for a HARM score < 2 to 15.1 ± 12.2 days for a HARM score > 4 (p < 0.001). In elective admissions, for HARM categories of < 2, 2-< 3, 3-4, and > 4, complication rates were 9.3, 23.2, 38.8, and 71.6%, respectively. There was a similar trend for increasing HARM score in emergent admissions as well. For all surgical procedure categories, increasing HARM score, with and without risk adjustment, correlated with increasing severity of complications by Clavien-Dindo classification. CONCLUSIONS: The HARM score is an easy-to-use quality metric that correlates with increasing complication rates and complication severity across multiple surgical disciplines when evaluated on a large administrative database. This inexpensive tool could be adopted across multiple institutions to compare the quality of surgical care.

Combination of Oral Antibiotics and Mechanical Bowel Preparation Reduces Surgical Site Infection in Colorectal Surgery.

BACKGROUND: Surgical site infections (SSI) are a common complication after colorectal surgery. An infection prevention bundle (IPB) was implemented to improve outcomes. STUDY DESIGN: A standardized IPB that included the administration of oral antibiotics with a mechanical bowel preparation, preoperative shower with chlorhexidine, hair removal and skin preparation in holding, antibiotic wound irrigation, and a "clean-closure" protocol was implemented in January 2013. Data from the American College of Surgeons NSQIP were analyzed at a single academic institution to compare pre-IPB and post-IPB SSI rates. In January 2014, a prospective database was implemented to determine compliance with individual IPB elements and their effect on outcomes. RESULTS: For the 24 months pre-IPB, the overall SSI rate was 19.7%. During the 30 months after IPB implementation, the SSI rate decreased to 8.2% (p < 0.0001). A subset of 307 patients was identified in both NSQIP and our prospective compliance databases. Elements of IPB associated with decreased SSI rates included preoperative shower with chlorhexidine (4.6% vs 16.2%; p = 0.005), oral antibiotics (3.4% vs 15.4%; p < 0.001), and mechanical bowel preparation (4.4% vs 14.3%; p = 0.008). Patients who received a full bowel preparation of both oral antibiotics and a mechanical bowel preparation had a 2.7% SSI rate compared with 15.8% for all others (p < 0.001). On multivariate analysis, full bowel preparation was independently associated with significantly fewer SSI (adjusted odds ratio 0.2; 95% CI 0.1 to 0.9; p = 0.006). CONCLUSIONS: Implementation of an IPB was successful in decreasing SSI rates in colorectal surgery patients. The combination of oral antibiotics with a mechanical bowel preparation was the strongest predictor of decreased SSI.

Disruption of retinoblastoma protein expression in the intestinal epithelium impairs lipid absorption.

We previously demonstrated increased villus height following genetic deletion, or knockout, of retinoblastoma protein (Rb) in the intestinal epithelium (Rb-IKO). Here we determined the functional consequences of augmented mucosal growth on intestinal fat absorption and following a 50% small bowel resection (SBR). Mice with constitutively disrupted Rb expression in the intestinal epithelium (Rb-IKO) along with their floxed (wild-type, WT) littermates were placed on a high-fat diet (HFD, 42% kcal fat) for 54 wk. Mice were weighed weekly, and fat absorption, indirect calorimetry, and MRI body composition were measured. Rb-IKO mice were also subjected to a 50% SBR, followed by HFD feeding for 33 wk. In separate experiments, we examined intestinal fat absorption in mice with conditional (tamoxifen-inducible) intestinal Rb (inducible Rb-IKO) deletion. Microarray revealed that the transcriptional expression of lipid absorption/transport genes was significantly reduced in constitutive Rb-IKO mice. These mice demonstrated greater mucosal surface area yet manifested paradoxically impaired intestinal long-chain triglyceride absorption and decreased cholesterol absorption. Despite attenuated lipid absorption, there were no differences in metabolic rate, body composition, and weight gain in Rb-IKO and WT mice at baseline and following SBR. We also confirmed fat malabsorption in inducible Rb-IKO mice. We concluded that, despite an expanded mucosal surface area, Rb-IKO mice demonstrate impaired lipid absorption without compensatory alterations in energy homeostasis or body composition. These findings underscore the importance of delineating structural/functional relationships in the gut and suggest a previously unknown role for Rb in the regulation of intestinal lipid absorption.

Operative management of rib fractures in the setting of flail chest: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of studies comparing operative to nonoperative therapy in adult FC patients. Outcomes were duration of mechanical ventilation (DMV), intensive care unit length of stay (ICULOS), hospital length of stay (HLOS), mortality, incidence of pneumonia, and tracheostomy. BACKGROUND: Flail chest (FC) results in paradoxical chest wall movement, altered respiratory mechanics, and frequent respiratory failure. Despite advances in ventilatory management, FC remains associated with significant morbidity and mortality. Operative fixation of the flail segment has been advocated as an adjunct to supportive care, but no definitive clinical trial exists to delineate the role of surgery. METHODS: A comprehensive search of 5 electronic databases was performed to identify randomized controlled trials and observational studies (cohort or case-control). Pooled effect size (ES) or relative risk (RR) was calculated using a fixed or random effects model, as appropriate. RESULTS: Nine studies with a total of 538 patients met inclusion criteria. Compared with control treatment, operative management of FC was associated with shorter DMV [pooled ES: -4.52 days; 95% confidence interval (CI): -5.54 to -3.50], ICULOS (-3.40 days; 95% CI: -6.01 to -0.79), HLOS (-3.82 days; 95% CI: -7.12 to -0.54), and decreased mortality (pooled RR: 0.44; 95% CI: 0.28-0.69), pneumonia (0.45; 95% CI: 0.30-0.69), and tracheostomy (0.25; 95% CI: 0.13-0.47). CONCLUSIONS: As compared with nonoperative therapy, operative fixation of FC is associated with reductions in DMV, LOS, mortality, and complications associated with prolonged MV. These findings support the need for an adequately powered clinical study to further define the role of this intervention.

Ret heterozygous mice have enhanced intestinal adaptation after massive small bowel resection.

Intestinal adaptation is an important compensatory response to massive small bowel resection (SBR) and occurs because of a proliferative stimulus to crypt enterocytes by poorly understood mechanisms. Recent studies suggest the enteric nervous system (ENS) influences enterocyte proliferation. We, therefore, sought to determine whether ENS dysfunction alters resection-induced adaptation responses. Ret+/- mice with abnormal ENS function and wild-type (WT) littermates underwent sham surgery or 50% SBR. After 7 days, ileal morphology, enterocyte proliferation, apoptosis, and selected signaling proteins were characterized. Crypt depth and villus height were equivalent at baseline in WT and Ret+/- mice. In contrast after SBR, Ret+/- mice had longer villi (Ret+/- 426.7 ± 46.0 µm vs. WT 306.5 ± 7.7 µm, P < 0.001) and deeper crypts (Ret+/- 119 ± 3.4 µm vs. WT 82.4 ± 3.1 µm, P < 0.001) than WT. Crypt enterocyte proliferation was higher in Ret+/- (48.8 ± 1.3%) than WT (39.9 ± 2.1%; P < 0.001) after resection, but apoptosis rates were similar. Remnant bowel of Ret+/- mice also had higher levels of glucagon-like peptide 2 (6.2-fold, P = 0.005) and amphiregulin (4.6-fold, P < 0.001) mRNA after SBR, but serum glucagon-like peptide 2 protein levels were equal in WT and Ret+/- mice, and there was no evidence of increased c-Fos nuclear localization in submucosal neurons. Western blot confirmed higher crypt epidermal growth factor receptor (EGFR) protein levels (1.44-fold; P < 0.001) and more phosphorylated EGFR (2-fold; P = 0.003) in Ret+/- than WT mice after SBR. These data suggest that Ret heterozygosity enhances intestinal adaptation after massive SBR, likely via enhanced EGFR signaling. Reducing Ret activity or altering ENS function may provide a novel strategy to enhance adaptation attenuating morbidity in patients with short bowel syndrome.

p38 MAPK regulates Bax activity and apoptosis in enterocytes at baseline and after intestinal resection.

Increased apoptosis in crypt enterocytes is a key feature of intestinal adaptation following massive small bowel resection (SBR). Expression of the proapoptotic factor Bax has been shown to be required for resection-induced apoptosis. It has also been demonstrated that p38-α MAPK (p38) is necessary for Bax activation and apoptosis in vitro. The present studies were designed to test the hypothesis that p38 is a key regulator of Bax activation during adaptation after SBR in vivo. Enterocyte expression of p38 was deleted by tamoxifen administration to activate villin-Cre in adult mice with a floxed Mapk14 (p38-α) gene. Proximal 50% SBR or sham operations were performed on wild-type (WT) and p38 intestinal knockout (p38-IKO) mice under isoflurane anesthesia. Mice were killed 3 or 7 days after operation, and adaptation was analyzed by measuring intestinal morphology, proliferation, and apoptosis. Bax activity was quantified by immunoprecipitation, followed by Western blotting. After SBR, p38-IKO mice had deeper crypts, longer villi, and accelerated proliferation compared with WT controls. Rates of crypt apoptosis were significantly lower in p38-IKO mice, both at baseline and after SBR. Levels of activated Bax were twofold higher in WT mice after SBR relative to sham. In contrast, activated Bax levels were reduced by 67% in mice after p38 MAPK deletion. Deleted p38 expression within the intestinal epithelium leads to enhanced adaptation and reduced levels of enterocyte apoptosis after massive intestinal resection. p38-regulated Bax activation appears to be an important mechanism underlying resection-induced apoptosis.

Regulation of retinoblastoma protein (Rb) by p21 is critical for adaptation to massive small bowel resection.

BACKGROUND: Adaptation following massive intestinal loss is characterized by increased villus height and crypt depth. Previously, we demonstrated that p21-null mice do not adapt after small bowel resection (SBR). As retinoblastoma protein (Rb) levels are elevated in p21-null crypt cells, we first sought to determine whether Rb is required for normal adaptation. Next, we tested whether Rb expression is responsible for blocked adaptation in p21-nulls. METHODS: Genetically manipulated mice and wild-type (WT) littermates underwent either 50% SBR or sham operation. The intestine was harvested at 3, 7, or 28 days later and intestinal adaptation was evaluated. Enterocytes were isolated and protein levels evaluated by Western blot and quantified by optical density. RESULTS: Rb-null mice demonstrated increased villus height, crypt depth, and proliferative rate at baseline, but there was no further increase following SBR. Deletion of one Rb allele lowered Rb expression and restored resection-induced adaptation responses in p21-null mice. CONCLUSION: Rb is specifically required for resection-induced adaptation. Restoration of adaptation in p21-null mice by lowering Rb expression suggests a crucial mechanistic role for Rb in the regulation of intestinal adaptation by p21.