Magnitude of Preoperative C-Reactive Protein Elevation Is Associated With De Novo Crohn's Disease After Ileal Pouch-Anal Anastomosis in Patients With Severe Colitis.

BACKGROUND: Total proctocolectomy with ileal pouch-anal anastomosis has become the standard procedure for patients with medically refractory ulcerative colitis, although a subset will develop de novo Crohn's disease. OBJECTIVE: In this study, we investigated the association of preoperative C-reactive protein levels with the development of de novo Crohn's disease after ileal pouch-anal anastomosis. DESIGN: A prospectively maintained database of patients undergoing ileal pouch-anal anastomosis was reviewed. PATIENTS: Preoperative C-reactive protein levels were compared between patients who developed de novo Crohn's disease and those who did not. De novo Crohn's disease was defined as small-bowel inflammation proximal to the ileal pouch or perianal disease identified more than 3 months after ileostomy closure. To minimize the heterogeneity of the timing of preoperative C-reactive protein measurement and the severity of ulcerative colitis, only hospitalized patients who had proctocolectomy for severe ulcerative colitis were included in the study. MAIN OUTCOME MEASURES: Development of de novo Crohn's disease was analyzed. RESULTS: Of 105 patients, 23 (22%) developed de novo Crohn's disease. Having C-reactive protein in the third tertile significantly increased the risk of developing de novo Crohn's disease (HR 3.44, 95% CI 1.10- 10.70, p = 0.03) compared to in the first tertile. In a multivariable model, a C-reactive protein in the third or second tertile vs the first tertile and younger age was associated with the development of de novo Crohn's disease. LIMITATIONS: Limited to only hospitalized patients with severe ulcerative colitis. CONCLUSIONS: In hospitalized patients undergoing ileal pouch-anal anastomosis for medically refractory ulcerative colitis, higher preoperative C-reactive protein levels appear to increase the risk of developing de novo Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B750.LA MAGNITUD DE LA ELEVACIÓN PREOPERATORIA DE LA PROTEÍNA C REACTIVA SE ASOCIA CON APARICIÓN DE UNA ENFERMEDAD DE CROHN DE NOVO DESPUÉS DE UNA ANASTOMOSIS DE BOLSA ILEAL AL ANO EN PACIENTES CON COLITIS SEVERAANTECEDENTES:La proctocolectomía total con anastomosis bolsa ileal-anal se ha convertido en el procedimiento estándar para los pacientes con colitis ulcerativa refractaria al tratamiento médico, aunque un subgrupo desarrollará una enfermedad de Crohn de novo.OBJETIVO:En este estudio investigamos la asociación de los niveles de proteína C reactiva preoperatoria con el desarrollo de la enfermedad de Crohn de novo, después de la anastomosis bolsa ileal-anal.DISEÑO:Se revisó una base de datos recolectada en forma prospectiva, de pacientes sometidos a anastomosis bolsa ileal-anal.PACIENTES:Se compararon los niveles de proteína C reactiva preoperatoria entre los pacientes que desarrollaron la enfermedad de Crohn de novo y los que no la desarrollaron. La enfermedad de Crohn de novo se definió como una inflamación del intestino delgado proximal a la bolsa ileal o una enfermedad perianal identificada más de 3 meses después del cierre de la ileostomía. Para minimizar la heterogeneidad del momento de la medición de la proteína C reactiva preoperatoria y la gravedad de la colitis ulcerativa, solo se incluyeron en el estudio los pacientes hospitalizados que se sometieron a una proctocolectomía por colitis ulcerativa grave.PRINCIPALES MEDIDAS DE RESULTADO:se analizó el desarrollo de la enfermedad de Crohn de novo.RESULTADOS:De 105 pacientes, 23 (22%) desarrollaron enfermedad de Crohn de novo. Tener una proteína C reactiva en el tercer tercil aumentó significativamente el riesgo de desarrollar la enfermedad de Crohn de novo (HR 3,44, IC del 95%: 1,10-10,70, p = 0,03) en comparación con el primer tercil. En un modelo multivariable, una proteína C reactiva en el tercer o segundo tercil frente al primer tercil y una edad más joven se asoció con el desarrollo de la enfermedad de Crohn de novo.LIMITACIONES:Limitado solo a pacientes hospitalizados con colitis ulcerativa grave.CONCLUSIONES:En pacientes hospitalizados sometidos a anastomosis bolsa ileal-anal por colitis ulcerativa refractaria al tratamiento médico, niveles más elevados de proteína C reactiva preoperatoria parecen aumentar el riesgo de desarrollar enfermedad de Crohn de novo. Consulte Video Resumen en http://links.lww.com/DCR/B750. (Traducción-Eduardo Londoño-Schimmer).

Randomized Clinical Trial Comparing Laparoscopic Versus Ultrasound-Guided Transversus Abdominis Plane Block in Minimally Invasive Colorectal Surgery.

BACKGROUND: Transversus abdominis plane block may improve analgesia after colorectal surgery; however, techniques remain unstandardized and results are conflicting. OBJECTIVE: The purpose of this study was to compare laparoscopic and ultrasound-guided transversus abdominis plane block with no block in minimally invasive colorectal surgery. DESIGN: This was a randomized controlled trial. SETTINGS: The study was conducted at an urban teaching hospital. PATIENTS: Patients undergoing laparoscopic colorectal surgery were included. INTERVENTIONS: The intervention included 2:2:1 randomization to laparoscopic, ultrasound-guided, or no transversus abdominis plane block. MAIN OUTCOME MEASURES: Morphine use in the first 24 hours after surgery was measured. RESULTS: The study cohort included 107 patients randomly assigned to laparoscopic (n = 41), ultrasound-guided (n = 45), or no transversus abdominis plane block (n = 21). Mean age was 50.4 years (SD ± 18 y), and 50 patients (47%) were men. Laparoscopic transversus abdominis plane block was superior to ultrasound-guided (p = 0.007) and no transversus abdominis plane block (p = 0.007), with median (interquartile range) total morphine used in the first 24 hours postoperatively of 17.6 mg (6.6-33.9 mg), 34.0 mg (16.4-44.4 mg), and 31.6 mg (18.4-44.4 mg). At 48 hours, laparoscopic transversus abdominis plane block remained superior to ultrasound-guided (p = 0.03) and no transversus abdominis plane block (p = 0.007) with median (interquartile range) total morphine used at 48 hours postoperatively of 26.8 mg (15.5-45.8 mg), 44.0 mg (27.6-70.0 mg), and 60.8 mg (34.8-78.8 mg). Mean hospital stay was 5.1 ± 3.1 days without any intergroup differences. Overall complications were similar between groups. LIMITATIONS: Treatment teams were not blinded and there was operator dependence of techniques and variable timing of the blocks. CONCLUSIONS: Laparoscopic transversus abdominis plane block is superior to ultrasound-guided and no transversus abdominis plane block in achieving pain control and minimizing opioid use in the first 24 hours after colorectal surgery. A large, multicenter, randomized trial is needed to confirm our findings. See Video Abstract at http://links.lww.com/DCR/A822.

A prospective, randomized, noninferiority trial of steroid dosing after major colorectal surgery.

OBJECTIVE: To evaluate the safety of perioperative low-dose steroids (LDS) versus high-dose steroids (HDS) in steroid-treated patients with inflammatory bowel disease (IBD) undergoing major colorectal surgery. BACKGROUND: Corticosteroid-treated patients undergoing major colorectal surgery are commonly prescribed HDS to prevent perioperative adrenal insufficiency and cardiovascular collapse. There is little evidence to support this practice. METHODS: We performed a single-blinded noninferiority trial to compare perioperative hemodynamic instability in 92 steroid-treated IBD patients undergoing major colorectal surgery. Patients were randomly assigned to receive perioperative high-dose corticosteroids (HDS; hydrocortisone, 100 mg, intravenously 3 times daily, followed by taper) or low-dose corticosteroids (LDS; intravenous hydrocortisone equivalent to presurgical oral dosing, followed by taper). The primary outcome was the absence of postural hypotension on postoperative day 1, defined as a decrease in systolic blood pressure by 20 mm Hg after sitting from a supine position. RESULTS: The primary outcome, absence of postural hypotension on postoperative day 1, occurred in 95% of those randomized to receive high doses of corticosteroids compared with 96% of those who received low doses (noninferiority 95% confidence interval=-0.08 to 0.09; P=0.007). CONCLUSIONS: In IBD patients undergoing abdominal surgery, the incidence of postural hypotension or adrenal insufficiency is similar among those receiving high doses or low doses of corticosteroids in the perioperative period. To reduce complications associated with unnecessarily high doses of steroids, steroid-treated IBD patients undergoing major colorectal surgery should be treated with low doses of steroids in the perioperative period. (Clinicaltrials.gov ID# NCT01559675).

A prospective randomized controlled trial of sugared chewing gum on gastrointestinal recovery after major colorectal surgery in patients managed with early enteral feeding.

BACKGROUND: A number of small prospective studies with conflicting results have evaluated the effect of sugar-free chewing gum on postoperative GI recovery in patients initially maintained nil per os after major colorectal surgery. OBJECTIVE: We sought to evaluate the effect of sugared chewing gum in combination with early enteral feeding on recovery of GI function after major colorectal surgery to ascertain any additive effects of this combination. DESIGN: This was a randomized prospective study. SETTING: This study was conducted at a single-institution tertiary referral center. PATIENTS: Patients undergoing major colorectal surgery were included. INTERVENTIONS: Patients were randomly assigned to sugared chewing gum (Gum) (instructed to chew 3 times daily; 45 minutes each time for 7 days postoperatively) or No Gum after major colorectal surgery. MAIN OUTCOME MEASURES: The primary outcome measured was time to tolerating low residue diet without emesis for 24 hours. The secondary outcomes measured were time to flatus, time to bowel movement, postoperative hospital stay, postoperative pain, nausea, and appetite. RESULTS: One hundred fourteen patients (60 No Gum; 54 Gum) were included in our analysis after randomization. There was no significant difference in time to tolerating a low-residue diet, time to flatus, time to bowel movement, length of postoperative hospital stay, postoperative complications, postoperative pain, nausea, or appetite between patients assigned to Gum or No Gum. There was an increased incidence of bloating, indigestion, and eructation in the Gum group (13%) in comparison with the No Gum group (2%) (p = 0.03). LIMITATIONS: Study subjects and investigators were not blinded. Multiple types of operations may cause intergroup variability. CONCLUSIONS: There does not appear to be any benefit to sugared chewing gum in comparison with no gum in patients undergoing major colorectal surgery managed with early feeding in the postoperative period. There may be increased incidence of bloating, indigestion, and eructation, possibly related to swallowed air during gum chewing.

It Is Not Just Cosmesis: Straight Laparoscopy with Stoma Site Extraction Improves Outcomes in Ulcerative Colitis Patients Undergoing Total Colectomy.

Minimally invasive approaches to total abdominal colectomy (TAC) in ulcerative colitis (UC) patients include straight laparoscopy (SL), hand-assisted laparoscopic surgery (HALS), and robotics. In this study, short-term outcomes of patients undergoing SL and HALS TAC were compared. Prospectively collected data on UC patients undergoing TAC were tabulated. The study cohort included 36 (27%) patients in the SL group and 95 (73%) patients in the HALS group. The groups were comparable in terms of preoperative characteristics and demographics. The mean operative time was 151 (range, 73-225) minutes in the SL group versus 164 (range, 103-295) minutes in the HALS group (P = 0.09). Total 48-hour IV morphine use was 30 (range, 0-186) mg in the SL group compared with 56 (0-275) mg in the HALS group (P < 0.01). Although overall morbidity was comparable between the groups, Clavien-Dindo Class III complications did not occur in any of the SL group patients versus 11 (11%) of the HALS group patients (P = 0.03). The postoperative length of stay was 3 (3-21) days in the SL group versus 5 (3-15) days in the HALS group (P < 0.01). Compared with HALS, SL is associated with lower postoperative narcotic use and hospital length of stay in UC patients undergoing TAC.

Synthesis and in vitro Biological Evaluation of Novel Thymidine Analogs Containing 1H-1,2,3-Triazolyl, 1H-Tetrazolyl, and 2H-Tetrazolyl Fragments.

3'-Azidothymidine (AZT) reacts with 1-propargyl-5-R-1H- and 2-propargyl-5-R-2H-tetrazoles (R = H, Me, CH2COOEt, CH2CON(CH3)2, Ph, 2-CH3-C6H4, or 4-NO2-C6H4) via the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition to give 3'-modified thymidine analogs incorporating 1H-1,2,3-triazolyl, 1H-, and 2H-tetrazolyl fragments in 41-76% yield. The structures of the obtained compounds have been elucidated by means of HRESI+-MS, 1H and 13 C{1H} NMR, and single crystal X-ray diffraction {for 3'-[4-(1H-5-N,N-dimethylaminocarbonylmethyltetrazol-1-yl)-1H-1,2,3-triazol-1-yl]thymidine 10d}. In vitro biological evaluation of the prepared compounds has been performed; they have exhibited low activity against phenotypic HIV-1899A. Moderate anti-influenza activity against influenza virus A/Puerto Rico/8/34 (H1N1) strain has been observed in the cases of 3'-(4-(1H-tetrazol-1-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 10a (IC50 39.6 µg/mL), 3'-(4-(2H-5-ethoxycarbonyltetrazol-2-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 11c (IC50 31.6 µg/mL), and 3'-(4-(2H-5-(4-nitrophenyl)-tetrazol-2-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 11g (IC50 46.4 µg/mL). The tested compounds possess very low cytotoxicity towards MDCK and MT4 cells as well as tumor human cervical carcinoma HeLa and promyelocytic leukemia HL-60 cells.

Practice Changes in Postoperative Feeding after Elective Colorectal Surgery: From Prospective Randomized Study to Everyday Practice.

Early postoperative feeding is the standard of care after colorectal surgery and is associated with improved outcomes. A controlled study performed at our center demonstrated faster bowel function recovery and shorter hospital stay without an increase in postoperative morbidity for a solid versus clear-liquid diet on postoperative day (POD) 1 after colorectal surgery. The present study aims to evaluate the impact of these findings on the practice of diet advancement by board-certified general surgeons (GS) and colorectal surgeons (CRS) at an urban teaching hospital. Patients undergoing elective colorectal surgery were prospectively evaluated. Data were compared with that of a study cohort that underwent elective colorectal surgery reported in 2012. Early postoperative feeding in the more recent cohort statistically increased for all cases on POD 0 and POD 1. Diet advancement over time revealed significant changes in early feeding on POD 0 for patients operated on by CRS (0% vs 83%; P < 0.0001) but not GS (13% vs 13%; P = 1). Patients operated on by either CRS or GS and offered early feeding on POD 1 did not significantly differ between time periods. Despite well-documented evidence of the advantages of early feeding, GS, but not CRS, remain reluctant to administer early diets to patients after colorectal surgery.

Tumor-associated DNA mutation detection in individuals undergoing colonoscopy.

The majority of colorectal cancers (CRC) harbor somatic mutations and epigenetic modifications in the tumor tissue, and some of these mutations can be detected in plasma as circulating tumor DNA (ctDNA). Precancerous colorectal lesions also contain many of these same mutations. This study examined plasma for ctDNA from patients undergoing a screening or diagnostic colonoscopy to determine the sensitivity and specificity of the ctDNA panel for detecting CRC and precancerous lesions. Two hundred patients without a history of nonskin cancer had blood drawn before a colonoscopy. Plasma ctDNA was measured with a 96 mutation panel for nine cancer driver genes. The ctDNA results were correlated with the findings at colonoscopy. Of the 200 patients, 176 (88%) had wild-type DNA, 12 (6%) had mutations detected, and 12 (6%) had indeterminate results. Colonoscopy was normal in 80% of the patients and 20% were found to have polyps. No CRC was found in this study, precluding a determination of true-positive rate for CRC detection. Our ctDNA panel was positive in 13.2% of patients with colonic polyps found at colonoscopy, while 4.7% of patients with normal colonoscopy also had ctDNA detected, which may represent ctDNA released from a benign process, an occult tumor, or an acquired somatic mutation from clonal hematopoiesis.

Postoperative Outcomes in Ustekinumab-Treated Patients Undergoing Abdominal Operations for Crohn's Disease.

BACKGROUND: Ustekinumab, a monoclonal antibody targeting interleukins-12 and -23 is used to treat adults with Crohn's disease [CD]. We determined the 30-day postoperative infectious complication rate among CD patients who received ustekinumab within the 12 weeks prior to an abdominal operation as compared with patients who received anti-tumor necrosis factor [TNF] agents. METHODS: A retrospective chart review of adults with CD who underwent an abdominal operation between January 1, 2015 and May 1, 2017 was performed across six sites. Surgical site infection [SSI] was defined as superficial skin and soft tissue infection, intra-abdominal abscess, anastomotic leak, and mucocutaneous separation of the stoma. RESULTS: Forty-four patients received ustekinumab and 169 patients received anti-TNF therapy within the 12 weeks prior to surgery. The two groups were similar, except anti-TNF patients were more likely to have received combination therapy with an immunomodulator [P = 0.006]. There were no significant differences in postoperative SSI [13% in ustekinumab versus 20% in anti TNF-treated patients, p = 0.61] or hospital readmission rates [18% versus 10%, respectively, p = 0.14], but ustekinumab-treated patients had a higher rate of return to the operating room [16% versus 5%; P = 0.01]. There were no significant predictors identified on multivariable analysis. CONCLUSIONS: Of the 44 patients with CD who received ustekinumab within the 12 weeks prior to a major abdominal operation, 13% experienced a 30-day postoperative SSI, not statistically different from the 20% found in the anti-TNF cohort. Ustekinumab treatment within 12 weeks of surgery does not appear to increase the risk of postoperative SSI above that of CD patients treated with anti-TNF medications.