Feasibility Trial of Intensity Modulated Proton Therapy to Reduce Toxicity in Anal Cancer Patients.

PURPOSE: The purpose of this trial was to assess the patient and physician-reported toxicity in anal cancer patients undergoing definitive chemoradiation with intensity-modulated proton therapy (IMPT). METHODS: Patients with stage II and III anal cancer were treated with IMPT. All patients received 2 cycles of 5-fluorouracil and mitomycin concurrently with radiation. Toxicity was assessed at baseline, weekly during chemoradiation, and in follow-up using physician-graded common terminology criteria for adverse events (CTCAE) v 4.0 and PRO-CTCAE. The primary endpoint was to define point estimates and 95% CI for acute ≥ grade 2/3 gastrointestinal (GI), genitourinary (GU), dermatologic, and hematologic toxicity. The proportion of PRO-CTCAE questions scored ≥3 for each domain was compared with the baselinse. The proportion of ≥ grade 2 and ≥ grade 3 toxicities were compared with historic intensity-modulated radiotherapy patients treated on RTOG 0529. RESULTS: Fourteen patients were enrolled from 2017 to 2020. Rates of physician-reported GI, GU, dermatologic, and hematologic toxicity were not significantly different between patients treated with IMPT compared with patients treated with intensity-modulated radiotherapy. Rates of patient-reported dermatologic and GU toxicity were low at baseline with a peak at week 6 (91% and 58% PRO-CTCAE items ≥ grade 3, respectively) and normalization to baseline 3 months after IMPT. In contrast, the proportion of high-grade PRO-CTCAE GI scores was 40% at baseline, which persisted through 1-year posttreatment. CONCLUSIONS: Clinician-reported toxicity was not improved with IMPT in the context of this underpowered trial. High-grade GI symptoms persisted for 12 months and were similar to baseline. Additional measures are needed to minimize acute and chronic toxicity related to chemoradiation.

Use of fluorescence imaging and indocyanine green during colorectal surgery: Results of an intercontinental Delphi survey.

BACKGROUND: Fluorescence imaging with indocyanine green is increasingly being used in colorectal surgery to assess anastomotic perfusion, and to detect sentinel lymph nodes. METHODS: In this 2-round, online, Delphi survey, 35 international experts were asked to vote on 69 statements pertaining to patient preparation and contraindications to fluorescence imaging during colorectal surgery, indications, technical aspects, potential advantages/disadvantages, and effectiveness versus limitations, and training and research. Methodological steps were adopted during survey design to minimize risk of bias. RESULTS: More than 70% consensus was reached on 60 of 69 statements, including moderate-strong consensus regarding fluorescence imaging's value assessing anastomotic perfusion and leak risk, but not on its value mapping sentinel nodes. Similarly, although consensus was reached regarding most technical aspects of its use assessing anastomoses, little consensus was achieved for lymph-node assessments. Evaluating anastomoses, experts agreed that the optimum total indocyanine green dose and timing are 5 to 10 mg and 30 to 60 seconds pre-evaluation, indocyanine green should be dosed milligram/kilogram, lines should be flushed with saline, and indocyanine green can be readministered if bright perfusion is not achieved, although how long surgeons should wait remains unknown. The only consensus achieved for lymph-node assessments was that 2 to 4 injection points are needed. Ninety-six percent and 100% consensus were reached that fluorescence imaging will increase in practice and research over the next decade, respectively. CONCLUSION: Although further research remains necessary, fluorescence imaging appears to have value assessing anastomotic perfusion, but its value for lymph-node mapping remains questionable.

Omission of Adjuvant Chemotherapy in Rectal Cancer Patients with Pathologic Complete Response: a National Analysis.

BACKGROUND: An increasing number of patients achieve a pathologic complete response (pCR) after neoadjuvant chemoradiation for locally advanced rectal cancer. Consensus guidelines continue to recommend oncologic resection followed by adjuvant chemotherapy in these patients. We hypothesize that there is significant variability in compliance with this recommendation. METHODS: The National Cancer Database was queried from 2006 to 2015 for patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiation followed by oncologic resection with a pCR (ypT0N0). Hierarchical logistic regression models were used to generate risk and reliability-adjusted rates of adjuvant chemotherapy utilization in patients with pCR at each hospital. RESULTS: In total, 2421 pCR patients were identified. Five-year overall survival was improved in pCR patients who received adjuvant chemotherapy compared with those who did not (92 vs. 85%, p < 0.01). Multivariate analysis indicated that improvement in overall survival remained associated with adjuvant chemotherapy (HR 0.60, 95% CI 0.44-0.82, p < 0.01). The mean adjuvant chemotherapy utilization rate among hospitals was 32%. There was an upward trend in use over the past decade, but two-thirds still do not receive the recommended therapy. High chemotherapy utilizer hospitals were more likely to be academic centers (54.9 vs. 45.9%, p < 0.01) when compared with low chemotherapy utilizers. CONCLUSION: Adjuvant chemotherapy is associated with improved survival in rectal cancer patients with pCR following neoadjuvant chemoradiation and oncologic resection. However, utilization among centers in the USA was only 32% with significant variability across centers. National efforts are needed to standardize treatment patterns according to national guidelines.

The impact of preoperative opioid use on outcomes after elective colorectal surgery: A propensity-matched comparison study.

BACKGROUND: The impact of recent preoperative opioid exposure on outcomes of colorectal surgery is unclear. Our aim was to evaluate the impact of preoperative opioid use on outcomes and opioid prescribing patterns after colorectal surgery. METHODS: We performed a retrospective review of all patients undergoing elective resection at a single institution from 2015 to 2017. Primary outcomes included in-hospital narcotic use and cost. Secondary outcomes included postoperative surgical outcomes and discharge prescribing patterns. RESULTS: A total of 390 patients underwent elective colorectal surgery, of whom 63 (16%) had a recent history of preoperative opioid use. Opioid users had similar age, sex, American Society of Anesthesiologists score, and operative indication compared with opioid-naïve patients (P > .05 for each). Postoperatively, the 30-day readmission rate was greater among opioid users (18% vs 9%, P = .03). Opioid users had greater total narcotic use (218 morphine milligram equivalents vs 111 morphine milligram equivalents, P = .04) and direct costs ($11,165 vs $8,911, P < .01). These patients were also more likely to require an opioid prescription on discharge (90% vs 68%, P < .01) and an opioid refill within 30 days (54% vs 21%, P < .01). CONCLUSION: Recent preoperative opioid exposure among colorectal surgery patients was associated with increased opioid consumption and costs. Moreover, unadjusted analysis was pertinent for more readmissions after surgery among preoperative opioid users. This work underscores the negative impact of preoperative, chronic opioid use on surgical outcomes and highlights the need for developing protocols to minimize perioperative narcotics.

Challenges in IBD Research: Pragmatic Clinical Research.

Pragmatic clinical research is part of five focus areas of the Challenges in IBD research document, which also includes preclinical human IBD mechanisms, environmental triggers, novel technologies, and precision medicine. The Challenges in IBD research document provides a comprehensive overview of current gaps in inflammatory bowel diseases (IBD) research and delivers actionable approaches to address them. It is the result of multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient centric research prioritization. In particular, the pragmatic clinical research section is focused on highlighting gaps that need to be addressed in order to optimize and standardize IBD care. Identified gaps include: 1) understanding the incidence and prevalence of IBD; 2) evaluating medication positioning to increase therapeutic effectiveness; 3) understanding the utility of therapeutic drug monitoring (TDM); 4) studying pain management; and 5) understanding healthcare economics and resources utilization. To address these gaps, there is a need to emphasize the use of emerging data sources and real-world evidence to better understand epidemiologic and therapeutic trends in IBD, expanding on existing data to better understand how and where we should improve care. Proposed approaches include epidemiological studies in ethnically and geographically diverse cohorts to estimate incidence and prevalence of IBD and impact of diversity on treatment patterns and outcomes. The implementation of new clinical trial design and methodologies will be essential to evaluate optimal medication positioning, appropriate use of TDM in adults and children, and multidisciplinary approaches to IBD pain management and its impact on healthcare resources.

Enhanced recovery protocol improves postoperative outcomes and minimizes narcotic use following resection for colon and rectal cancer.

BACKGROUND: Enhanced recovery protocols are associated with improved recovery. However, data on outcomes following the implementation of an enhanced recovery protocol in colorectal cancer are limited. We set out to study the postoperative outcomes, opioid use patterns, and cost impact for patients undergoing colon or rectal resection for cancer. METHODS: A retrospective review of all elective colorectal cancer resections from January 2015 to June 2018 at a single institution was performed. Patient demographics, operative details, and postoperative outcomes were collected. Colon and rectal patients were studied separately, with comparison of patients before and after the implementation of an enhanced recovery protocol. RESULTS: One hundred ninety-two patients underwent elective colorectal resection for cancer. In January 2016, an enhanced recovery protocol was implemented for all elective resections - 71 patients (33 colon and 38 rectal) underwent surgery before implementation and 121 patients (56 colon and 65 rectal) underwent surgery after implementation of the enhanced recovery protocol. There were no differences with regard to age, gender, or body mass index before or after implementation (all P > .05). For both colon and rectal cancer patients, the enhanced recovery protocol reduced time to regular diet (both P < .05) and length of stay (colon: 3 vs 4 days; rectal: 4 vs 6 days; both P < .01). Enhanced recovery protocol patients also consumed fewer total narcotics (colon: 44 vs 184 morphine milligram equivalents, P < .01; rectal: 121 vs 393 morphine milligram equivalents, P < .01). CONCLUSIONS: Enhanced recovery protocol use reduced length of stay and narcotic use with similar total costs and no difference in 30-day complications for both colon and rectal cancer resections.

Enhanced Recovery after Colorectal Surgery: Can We Afford Not to Use It?

BACKGROUND: Enhanced recovery pathways (ERPs) aim to reduce length of stay without adversely affecting short-term outcomes. High pharmaceutical costs associated with ERP regimens, however, remain a significant barrier to widespread implementation. We hypothesized that ERP would reduce hospital costs after elective colorectal resections, despite the use of more expensive pharmaceutical agents. STUDY DESIGN: An ERP was implemented in January 2016 at our institution. We collected data on consecutive colorectal resections for 1 year before adoption of ERP (traditional, n = 160) and compared them with consecutive resections after universal adoption of ERP (n = 146). Short-term surgical outcomes, total direct costs, and direct hospital pharmacy costs were compared between patients who received the ERP and those who did not. RESULTS: After implementation of the ERP, median length of stay decreased from 5.0 to 3.0 days (p < 0.01). There were no differences in 30-day complications (8.1% vs 8.9%) or hospital readmission (11.9% vs 11.0%). The ERP patients required significantly less narcotics during their index hospitalization (211.7 vs 720.2 morphine equivalence units; p < 0.01) and tolerated a regular diet 1 day sooner (p < 0.01). Despite a higher daily pharmacy cost ($477 per day vs $318 per day in the traditional cohort), the total direct pharmacy cost for the hospitalization was reduced in ERP patients ($1,534 vs $1,859; p = 0.016). Total direct cost was also lower in ERP patients ($9,791 vs $11,508; p = 0.004). CONCLUSIONS: Implementation of an ERP for patients undergoing elective colorectal resection substantially reduced length of stay, total hospital cost, and direct pharmacy cost without increasing complications or readmission rates. Enhanced recovery pathway after colorectal resection has both clinical and financial benefits. Widespread implementation has the potential for a dramatic impact on healthcare costs.

Combination oral and mechanical bowel preparations decreases complications in both right and left colectomy.

BACKGROUND: Before elective colectomy, many advocate mechanical bowel preparation with oral antibiotics, whereas enhanced recovery pathways avoid mechanical bowel preparations. The optimal preparation for right versus left colectomy is also unclear. We sought to determine which strategy for bowel preparation decreases surgical site infection (SSI) and anastomotic leak (AL). METHODS: Elective colectomies from the National Surgical Quality Improvement Program colectomy database (2012-2015) were divided by (1) type of bowel preparation: no preparation (NP), mechanical preparation (MP), oral antibiotics (PO), or mechanical and oral antibiotics (PO/MP); and (2) type of colonic resection: right, left, or segmental colectomy. Univariate and multivariate analyses identified predictors of SSI and AL, and their risk-adjusted incidence was determined by logistic regression. RESULTS: When analyzed as the odds ratio compared with NP, the PO and PO/MP groups were associated with a decrease in SSI (PO = 0.70 [0.55-0.88] and PO/MP = 0.47 [0.42-0.53]; P < .01). Use of PO/MP was associated with a decrease in SSI across all types of resections (right colectomy = 0.40 [0.33-0.50], left colectomy = 0.57 [0.47-0.68], and segmental colectomy = 0.43 (0.34-0.54); P < .01). Similarly, use of PO/MP was associated with a decrease in AL in left colectomy = 0.50 ([0.37-0.69]; P < .01) and segmental colectomy = 0.53 ([0.36-0.80]; P < .01). CONCLUSION: Mechanical bowel preparation with oral antibiotics is the preferred preoperative preparation strategy in elective colectomy because of decreased incidence of SSI and AL.

Emerging Trends in the Etiology, Prevention, and Treatment of Gastrointestinal Anastomotic Leakage.

Anastomotic leaks represent one of the most alarming complications following any gastrointestinal anastomosis due to the substantial effects on post-operative morbidity and mortality of the patient with long-lasting effects on the functional and oncologic outcomes. There is a lack of consensus related to the definition of an anastomotic leak, with a variety of options for prevention and management. A number of patient-related and technical risk factors have been found to be associated with the development of an anastomotic leak and have inspired the development of various preventative measures and technologies. The International Multispecialty Anastomotic Leak Global Improvement Exchange group was convened to establish a consensus on the definition of an anastomotic leak as well as to discuss the various diagnostic, preventative, and management measures currently available.

Dynamic Article: Percutaneous Nerve Evaluation Versus Staged Sacral Nerve Stimulation for Fecal Incontinence.

BACKGROUND: Sacral neuromodulation using a 2-staged approach is an established therapy for fecal incontinence. Office-based percutaneous nerve evaluation is a less-invasive alternative to the stage 1 procedure but is seldom used in the evaluation of patients with fecal incontinence. OBJECTIVE: The aim of this study was to determine the clinical success of percutaneous nerve evaluation versus a staged approach. DESIGN: This was a retrospective review of a prospectively maintained, single-institution database of patients treated with sacral neuromodulation for fecal incontinence. SETTINGS: This study was conducted at a single academic medical center. PATIENTS: Eighty-six consecutive patients were treated with sacral neuromodulation for fecal incontinence. INTERVENTIONS: Percutaneous nerve evaluation was compared with a staged approach. MAIN OUTCOME MEASURES: The primary outcome measured was the proportion of patients progressing to complete implantation based on >50% improvement in Wexner score during the testing phase. RESULTS: Percutaneous nerve evaluation was performed in 45 patients, whereas 41 underwent a staged approach. The mean baseline Wexner score did not differ between testing groups. Success was similar between the staged approach and percutaneous nerve evaluation (90.2% versus 82.2%; p = 0.36). The mean 3-month Wexner score was not significantly different between testing methods (4.4 versus 4.1; p = 0.74). However, infection was more likely to occur after the staged approach (10.5% versus 0.0%; p < 0.05). LIMITATIONS: This study was limited by its retrospective nature and potential for selection bias. CONCLUSIONS: Percutaneous nerve evaluation offers a viable alternative to a staged approach in the evaluation of patients for sacral neuromodulation in the setting of fecal incontinence. Not only are success rates similar, but percutaneous nerve evaluation also has the benefit of limiting patients to 1 operating room visit and has lower rates of infection as compared with the traditional staged approach for sacral neuromodulation.

Laparoscopic sigmoid colectomy: Are all laparoscopic techniques created equal?

BACKGROUND: Laparoscopic colectomy has been associated with improved postoperative pain control, earlier return to work, and shorter hospital stays compared to open colectomy. However, there are varied technical approaches to laparoscopic resections. We therefore sought to determine whether the straight laparoscopic approach was associated with shorter length of stay compared to hand-assisted and laparoscopic-assisted techniques for sigmoid colectomies. METHODS: A retrospective review of laparoscopic sigmoid colectomies performed by five colorectal surgeons from 2010 to 2014 was performed. Approaches were defined as: (1) straight laparoscopic if colon mobilization, inferior mesenteric artery transection and intra-corporeal anastomosis were performed laparoscopically, (2) hand assisted if a hand port was utilized to assist with mobilization and vessel transection, and (3) laparoscopic assisted if only the colon mobilization was performed intra-corporeally. Poisson regression was performed to determine the impact of surgical technique on LOS while controlling for differences in patient factors. RESULTS: A total of 191 patients were identified with 71 straight laparoscopic, 57 hand-assisted, and 63 laparoscopic-assisted cases. Substantial variability in choice of surgical technique was seen across surgeons. Patient populations were similar, with the exception of hand-assisted procedures being more often used in obese patients. Unadjusted average postoperative days to discharge were 3.6 days for straight laparoscopic and 4.1 and 4.0 days for hand-assisted and laparoscopic-assisted approaches, respectively. While controlling for factors associated with longer hospital stay, the straight laparoscopic approach was associated with a 14 % shorter stay compared to laparoscopic-assisted colectomy and a 15 % shorter stay compared to hand-assisted colectomy. The straight laparoscopic approach was also associated with earlier return of bowel function compared to other approaches. CONCLUSIONS: The straight laparoscopic approach to sigmoid colectomy is associated with substantially shorter postoperative stay and earlier return of bowel function when compared to hand-assisted and laparoscopic-assisted techniques. When technically feasible, the straight laparoscopic approach is preferred.

In the Absence of a Mechanical Bowel Prep, Does the Addition of Pre-Operative Oral Antibiotics to Parental Antibiotics Decrease the Incidence of Surgical Site Infection after Elective Segmental Colectomy?

BACKGROUND: Pre-operative oral antibiotics administered the day prior to elective colectomy have been shown to decrease the incidence of surgical site infections (SSI) if a mechanical bowel prep (MBP) is used. Recently, the role for mechanical bowel prep has been challenged as being unnecessary and potentially harmful. We hypothesize that if MBP is omitted, oral antibiotics do not alter the incidence of SSI following colectomy. METHODS: We selected patients who underwent an elective segmental colectomy from the 2012 and 2013 National Surgical Quality Improvement Program colectomy procedure targeted database. Indications for surgery included colon cancer, diverticulitis, inflammatory bowel disease, or benign polyp. Patients who received mechanical bowel prep were excluded. The primary outcome measured was surgical site infection, defined as the presence of superficial, deep or, organ space infection within 30 d from surgery. RESULTS: A total of 6,399 patients underwent elective segmental colectomy without MBP. The incidence of SSI differed substantially between patients who received oral antibiotics, versus those who did not (9.7% vs. 13.7%, p=0.01). Multivariate analysis indicated that age, smoking status, operative time, perioperative transfusions, oral antibiotics, and surgical approach were associated with post-operative SSI. When controlling for confounding factors, the use of pre-operative oral antibiotics decreased the incidence of surgical site infection (odds ratio=0.66, 95% confidence interval=0.48-0.90, p=0.01). CONCLUSION: Even in the absence of mechanical bowel prep, pre-operative oral antibiotics appear to reduce the incidence of surgical site infection following elective colectomy.

Practice Guideline for the Surveillance of Patients After Curative Treatment of Colon and Rectal Cancer.

Current evidence suggests improved rates of curative secondary treatment following identification of recurrence among patients who participate in a surveillance program after initial curative resection of colon or rectal cancer. The newer data show that surveillance CEA, chest and liver imaging,and colonoscopy can also improve survival through early diagnosis of recurrence; thus, these modalities are now included in the current guideline. Although the optimum strategy of surveillance for office visits, CEA, chest and liver imaging, and colonoscopy is not yet defined, routine surveillance does improve the detection of recurrence that can be resected with curative intent. Recommended surveillance schedules are shown in Table 4. However, the factors to be considered when recommending surveillance include underlying risk for recurrence, patient comorbidity, and the ability to tolerate major surgery to resect recurrent disease or palliative chemotherapy, performance status, physiologic age, preference, and compliance. The success of surveillance for early detection of curable recurrence will depend on patient and provider involvement to adhere to the surveillance schedule and avoid unnecessary examination. It should be noted that, after curative resection of colorectal cancer, patients are still at risk for other common malignancies(lung, breast, cervix, prostate) for which standard screening recommendations should be observed and measures to maintain general health (risk reduction for cardiovascular disease, eg, cessation of smoking, control of blood pressure and diabetes mellitus, balanced diet, regular exercise and sleep, and flu vaccines) should be recommended.

Does preoperative anal physiology testing or ultrasonography predict clinical outcome with sacral neuromodulation for fecal incontinence?

INTRODUCTION AND HYPOTHESIS: To determine the value of preoperative anal physiology testing and transanal ultrasonography in predicting clinical response to sacral neuromodulation for fecal incontinence. METHODS: We report a retrospective study of all patients treated with sacral neuromodulation for fecal incontinence in a single practice between 2011 and 2014 was performed. Patient demographics included age, gender, comorbidities, presence of an ultrasound-defined external sphincter defect, and history of prior anal sphincter repair. Cleveland Clinic Florida (CCF) scores were used to assess the severity of fecal incontinence at baseline, and at 3, 6 and 12 months. Pearson's correlation coefficient was used to evaluate the relationship between preoperative physiology testing and ultrasonography and patient outcome. RESULTS: Sacral neuromodulation was trialed in 60 patients, of whom 31 had anorectal physiology testing and 29 did not. Patients who were tested were younger (60.9 vs. 71.4 years, p = 0.013) and more likely to have had a prior overlapping sphincteroplasty (40.5% vs. 15%, p = 0.043). Among patients who progressed to complete system implantation, CCF scores at 3 and 12 months were similar whether they had physiology testing or not. Likewise, patient outcome did not correlate with the finding of an ultrasound-defined external sphincter defect. Pearson's correlation coefficient was used to evaluate the relationship between the test results and the 3-month CCF scores. CCF scores 3 months after full system implantation did not correlate with the presence or size of an external sphincter defect, resting or squeeze pressure, pudendal nerve terminal motor latency, rectoanal inhibitory reflex, or minimum detectable volume. CONCLUSIONS: Anal physiology testing and ultrasonography were not predictive of clinical outcomes among patients treated with sacral neuromodulation for fecal incontinence.