When is neoadjuvant chemotherapy indicated in rectal neuroendocrine tumors? An analysis of the National Cancer Database.

BACKGROUND: Rectal neuroendocrine tumors (rNET) are rare and challenging to manage. While most patients with small rNET can be definitively treated with local excision, the role of chemotherapy in general and neoadjuvant therapy particularly in managing advanced rNET has not been well established. Therefore, this study aimed to determine which patients with rNET may gain a survival benefit from neoadjuvant chemotherapy. METHODS: A retrospective cohort analysis of all patients who underwent surgical resection of rNET in the US National Cancer Database (NCDB) (2004-2019) was performed. First, univariate and multivariate Cox regression analyses were performed to determine the independent predictors of poor overall survival (OS) and define the high-risk groups. Afterward, stratified OS analyses were performed for each high-risk group to assess whether neoadjuvant chemotherapy had a survival benefit in each group. RESULTS: A total of 1837 patients (49.8% female; mean age 56.6 ± 12.3 years) underwent radical resection of a rNET. Tumors > 20 mm in size, clinical T4 tumors, poorly differentiated tumors, and metastatic disease were independent predictors of worse OS and were defined as high-risk groups. Neoadjuvant chemotherapy did not have a significant survival benefit in any of the high-risk groups, except for patients with high-grade rNETs where neoadjuvant therapy significantly improved OS to a mean of 30.9 months compared with 15.9 months when neoadjuvant therapy was not given (p = 0.006). CONCLUSIONS: Neoadjuvant chemotherapy improved the OS of patients with high-grade rNET by 15 months and may be indicated for this group.

A network meta-analysis of surgical treatments of complete rectal prolapse.

PURPOSE: Surgical treatment of complete rectal prolapse can be undertaken via an abdominal or a perineal approach. The present network meta-analysis aimed to compare the outcomes of different abdominal and perineal procedures for rectal prolapse in terms of recurrence, complications, and improvement in fecal incontinence (FI). METHODS: A PRISMA-compliant systematic review of PubMed, Scopus, and Web of Science was conducted. Randomized clinical trials comparing two or more procedures for the treatment of complete rectal prolapse were included. The risk of bias was assessed using the ROB-2 tool. The main outcomes were recurrence of full-thickness rectal prolapse, complications, operation time, and improvement in FI. RESULTS: Nine randomized controlled trials with 728 patients were included. The follow-up ranged between 12 and 47 months. Posterior mesh rectopexy had significantly lower odds of recurrence than did the Altemeier procedure (logOR, - 12.75; 95% credible intervals, - 40.91, - 1.75), Delorme procedure (- 13.10; - 41.26, - 2.09), resection rectopexy (- 11.98; - 41.36, - 0.19), sponge rectopexy (- 13.19; - 42.87, - 0.54), and sutured rectopexy (- 13.12; - 42.58, - 1.50), but similar odds to ventral mesh rectopexy (- 12.09; - 41.7, 0.03). Differences among the procedures in complications, operation time, and improvement in FI were not significant. CONCLUSIONS: Posterior mesh rectopexy ranked best with the lowest recurrence while perineal procedures ranked worst with the highest recurrence rates.

Outcomes of gracilis muscle interposition for rectourethral fistulas caused by treatment of prostate cancer.

BACKGROUND: Gracilis muscle interposition (GMI) has been associated with favorable outcomes in treating complex perianal fistulas. Outcomes of GMI may vary according to the fistula etiology, particularly between rectovaginal fistulas in women and rectourethral fistulas (RUF) in men. The aim of this study was to assess the outcome of GMI to treat RUF acquired after prostate cancer treatment. METHODS: This retrospective cohort study included male patients treated with GMI for RUF acquired after prostate cancer treatment between January 2000 and December 2018 in the Department of Colorectal Surgery, Cleveland Clinic Florida. The primary outcome was the success of GMI, defined as complete healing of RUF without recurrence. Secondary outcomes were length of hospital stay and postoperative complications. RESULTS: This study included 53 male patients with a median age of 68 (range, 46-85) years. Patients developed RUF after treatment of prostate cancer with radiation (52.8%), surgery (34%), or transurethral resection of the prostate (TURP) (13.2%). Median hospital stay was 5 (IQR, 4-7) days. Twenty (37.7%) patients experienced 25 complications, the most common being wound infection and dehiscence. Primary healing after GMI was achieved in 28 (52.8%) patients. Fifteen additional patients experienced successful healing of RUF after additional procedures, for a total success rate of 81.1%. Median time to complete healing was 8 (range, 4-56) weeks. The only significant factor associated with outcome of GMI was wound dehiscence (p = 0.008). CONCLUSIONS: Although the initial success rate of GMI was approximately 53%, it increased to 81% after additional procedures. Complications after GMI were mostly minor, with wound complications being the most common. Perianal wound dehiscence was significantly associated with failure of healing of RUF after GMI.

Outcomes of graciloplasty in the treatment of fecal incontinence: a systematic review and meta-analysis of the literature.

BACKGROUND: Patients with refractory fecal incontinence symptoms can be treated with several surgical procedures including graciloplasty. Reported outcomes and morbidity rates of this procedure are highly variable. The aim of this study was to assess continence rate and safety of dynamic and adynamic graciloplasty. METHODS: PubMed and Google Scholar databases were systematically searched from inception until January 2022 according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Reviews, animal studies, studies with patients < 18 years or < 10 patients, with no success rate reported or non-English text, were excluded. Main outcome measures were overall continence and morbidity rates of each technique. RESULTS: Fourteen studies were identified, incorporating a total of 450 patients (337 females), published between 1980 and 2021. Most common etiology of incontinence (35.5%-n = 160) was obstetric trauma followed by anorectal trauma (20%-n = 90). The weighted mean rate of continence after dynamic graciloplasty was 69.1% (95% CI 0.53-0.84%, I2 = 90%) compared to 71% (95% CI 0.54-0.87, I2 = 82.5%) after adynamic. Although the weighted mean short-term complication rate was lower in the dynamic group (26% versus 40%), when focusing on complications requiring intervention under general anesthesia, there was a much higher incidence (43.4% versus 10.5%) in the dynamic group. The weighted mean rate of long-term complications was 59.4% (95% CI 0.13-1.04%, I2 = 97.7%) in the dynamic group, almost twice higher than in the adynamic group [30% (95% CI - 0.03 to 0.63), I2 = 95.8%]. Median follow-up ranged from 1 to 13 years. CONCLUSIONS: Our data suggest that graciloplasty may be considered for incontinent patients. Dynamic graciloplasty may harbor higher risk for reoperation and complications compared to adynamic. The fact that the functional results between adynamic and dynamic graciloplasty are equivalent and the morbidity rate of adynamic graciloplasty is significantly lower reinforce the graciloplasty as an option to treat appropriately selected patients with fecal incontinence.

Biological therapy prior to repeat ileocolic resection in Crohn's disease can reduce the postoperative complication rate.

BACKGROUND: The aim of this study was to assess the effect of preoperative biologic therapy on the surgical outcome of Crohn's disease (CD) patients undergoing repeat ileocolic resection. METHODS: This was a retrospective analysis of all CD patients who underwent repeat ileocolic resection at Cleveland Clinic Florida between January 2011 and April 2021. Patients were divided into two groups: treatment biologic therapy prior to surgery and controls. RESULTS: Sixty-five patients (31males, median age 54 [range 23-82] years) were included in the study. Twenty nine (44.6%) were treated with biologic therapy prior to repeat ileocolic resection. No demographic differences were found between the biologic therapy and control groups. In addition, no differences were found in mean time from index ileocolic resection (p = 0.9), indication for surgery (p = 0.11), and preoperative albumin (p = 0.69). The majority of patients (57; 87.7%) were operated on laparoscopically, and mean overall operation time was 225 (SD 49.27) min. Overall, the postoperative complication rate was 43.1% (28 patients) and median length of stay was 5 (range 2-21) days. Postoperative complications were more common in the control group, compared to the biologic therapy group (55.6 vs 27.5%; p = 0.04). Conversion rate (35.7 vs 20.7%; p = 0.24), operation time (223 vs 219 min; p = 0.75), length of stay (5.2 vs 5.9 days; p = 0.4), and readmission (16.6 vs 11.1%; p = 0.72) were similar between the two groups. Multivariate analysis of risk factors for postoperative complications showed that biologic treatment was correlated with a lower risk (HR -0.28, CI 95% -0.5596 to -0.01898, p = 0.03). CONCLUSIONS: Patients treated with biologic therapy for CD who underwent repeat ileocolic resection had fewer postoperative complications.

Treatment of enterocutaneous fistula: a systematic review and meta-analysis.

BACKGROUND: Enterocutaneous fistula (ECF) is an abnormal communication between the gastrointestinal tract and skin, with a myriad of etiologies and therapeutic options. Management is influenced by etiology and specifics of the ECF, and patient-related factors. The aim of this study was to assess overall success, recurrence, and mortality rates of treatment for ECF. MATERIALS: A systematic search of PubMed and Google Scholar was performed through October 2021 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Case reports, reviews, animal studies, studies not reporting outcomes, had no available English text, included patients < 16 years old or those assessing other abdominocutaneous/internal fistulas were excluded. RESULTS: Fifty-three studies, between 1975 and 2020, incorporating 3078 patients were included. Patient age ranged between 16 and 87 years with a male:female ratio of 1.14:1. ECF developed postoperatively in 89.4%. Other common etiologies were inflammatory bowel disease, trauma, malignancy, and radiation. At least 28% of patients had complex fistulae (reported in 18 studies). Most common fistula site was small bowel. In 34 publications, 62.4% (n = 1371) patients received parenteral nutrition. In 45 publications, 72.5% underwent surgery to treat the fistula. Meta-analysis revealed an 89% healing rate; recurrence rate after initial successful treatment was 11.1%, and mortality rate was 8.5%. In a subgroup of patients who underwent combined ECF takedown and abdominal wall reconstructions (n = 315), 78% achieved fascial closure, mesh was used in 72%, hernia, and fistula recurrence rates were 19.7% and 7.6%, respectively. CONCLUSIONS: Treatment of ECF must be individualized according to specific etiology and location of the fistula and the patient's associated conditions.

External sphincter-sparing anal fistulotomy (ESSAF): a simplified technique for the treatment of fistula-in-ano.

BACKGROUND: Fistula-in-ano due to cryptoglandular disease is a common condition. While a simple anal fistula can be treated successfully by a fistulotomy, the risk of potential damage to the anal sphincters and subsequent poor functional outcomes persist in a large portion of patients with complex fistulae. Several sphincter-preserving treatment procedures have been described for complex fistulae over the past 3 decades, with variable results and complication rates, and no procedure is proven to be superior to the others. We developed external sphincter-sparing anal fistulotomy (ESSAF), a reproducible simple modification of the ligation of intersphincteric fistula tract (LIFT) technique for the treatment of complex fistula-in-ano.. The aim of the present study was to describe the technique and our outcomes. METHODS: This was a retrospective review of all patients who underwent ESSAF for a complex anal fistula at our institution from January 2014 to December 2019. The primary outcome measure of this study was the primary fistula healing rate. Secondary outcome measures included fecal and/or gas incontinence and postoperative complications. During the ESSAF procedure, the mucosa and skin overlying the fistula tract are incised to allow complete exposure of the sphincter complex. Then the internal sphincter muscle fibers overlying the tract are divided and the tract is meticulously curetted and debrided. Next, the internal opening of the tract traversing the external sphincter muscle is suture-ligated with absorbable sutures. Then, a minimal amount of mucosa is advanced and the incision is partially closed with absorbable sutures, while its external portion is left open for drainage. RESULTS: Fifty-nine patients [43 males, median age was 50 years (range 36-63 years)] underwent ESSAF for complex anal fistula during the study period. Mean follow-up was 12 ± 14.7 months. Of the 59 patients, 42 (71.2%) experienced fistula closure, with a median healing time of 8 weeks (IQR 4-16 weeks). None of the patients developed significant anal incontinence following the procedure. One patient (1.7%) suffered from soiling and another patient (1.7%) developed postoperative bleeding. There were no infectious complications. Of the 17 patients (28.8%) who failed to heal successfully, 9 (15.2%) did not heal primarily and 8 (16%) experienced recurrence after complete healing. Thirteen (76%) of these patients underwent reoperation with complete recovery after ESSAF (n = 4), fistulotomy (n = 8) or endorectal advancement flap (ERAF) (n = 1). Overall ESSAF initiated recovery in 93.2% of the patients. CONCLUSIONS: ESSAF is a feasible, safe, reproducible and effective sphincter-sparing procedure for the treatment of complex anal fistulae.

Does caffeine enhance bowel recovery after elective colorectal resection? A prospective double-blinded randomized clinical trial.

BACKGROUND: Postoperative ileus is a common condition following abdominal surgery. Previous studies have shown the positive effects of coffee on gastrointestinal motility. The aim of this study was to assess whether caffeine is the stimulatory agent in coffee that triggers bowel motility and thus may reduce the duration of postoperative ileus. METHODS: This was a single-centered, prospective, randomized controlled, double-blinded clinical trial. Patients scheduled to undergo elective laparoscopic colectomy between November 2017 and March 2019 were randomly assigned to receive either oral caffeine (100 mg three times daily) or placebo following the procedure. Primary endpoints were time to first flatus and time to first bowel movement. Secondary endpoints were time to tolerate a solid, low-residue diet and length of hospital stay. Registration number: NCT03097900. RESULTS: Seventy patients were included, [35 males, median age 56 years (range 19-79 years)]. After the exclusion of 12 patients, there were 30 patients in the caffeine group and 28 patients in the placebo group. The first passage of stool in the caffeine group occurred 18 h earlier than in the placebo group (p = 0.012); other endpoints did not reach statistical significance. No caffeine-related adverse events were observed. CONCLUSION: Caffeine consumption following colectomy is safe, leads to a significantly shorter time to first bowel movement, and may thus potentially lead to a shorter postoperative hospital stay.

Microbial and Viral Communities and Their Antibiotic Resistance Genes Throughout a Hospital Wastewater Treatment System.

Antibiotic resistance poses a serious threat to global public health, and antibiotic resistance determinants can enter natural aquatic systems through discharge of wastewater effluents. Hospital wastewater in particular is expected to contain high abundances of antibiotic resistance genes (ARGs) compared to municipal wastewater because it contains human enteric bacteria that may include antibiotic-resistant organisms originating from hospital patients, and can also have high concentrations of antibiotics and antimicrobials relative to municipal wastewater. Viruses also play an important role in wastewater treatment systems since they can influence the bacterial community composition through killing bacteria, facilitating transduction of genetic material between organisms, and modifying the chromosomal content of bacteria as prophages. However, little is known about the fate and connections between ARGs, viruses, and their associated bacteria in hospital wastewater systems. To address this knowledge gap, we characterized the composition and persistence of ARGs, dsDNA viruses, and bacteria from influent to effluent in a pilot-scale hospital wastewater treatment system in Israel using shotgun metagenomics. Results showed that ARGs, including genes conferring resistance to antibiotics of high clinical relevance, were detected in all sampling locations throughout the pilot-scale system, with only 16% overall depletion of ARGs per genome equivalent between influent and effluent. The most common classes of ARGs detected throughout the system conferred resistance to aminoglycoside, cephalosporin, macrolide, penam, and tetracycline antibiotics. A greater proportion of total ARGs were associated with plasmid-associated genes in effluent compared to in influent. No strong associations between viral sequences and ARGs were identified in viral metagenomes from the system, suggesting that phage may not be a significant vector for ARG transfer in this system. The majority of viruses in the pilot-scale system belonged to the families Myoviridae, Podoviridae, and Siphoviridae. Gammaproteobacteria was the dominant class of bacteria harboring ARGs and the most common putative viral host in all samples, followed by Bacilli and Betaproteobacteria. In the total bacterial community, the dominant class was Betaproteobacteria for each sample. Overall, we found that a variety of different types of ARGs and viruses were persistent throughout this hospital wastewater treatment system, which can be released to the environment through effluent discharge.