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.

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.

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.

Postoperative predictors of early discharge following laparoscopic segmental colectomy.

PURPOSE: There is increasing pressure to shorten length of stay (LOS) after major surgical procedures. Although laparoscopic colectomy has been shown to have shorter LOS than open colectomy, not all patients experience a short length of stay. Predictive factors for early discharge after laparoscopic colectomy have not been clearly defined. We hypothesized that patients who exhibit a brisk urine output and lack of a systemic inflammatory response on the first postoperative day would experience a shorter postoperative stay after laparoscopic colectomy. METHODS: We performed a retrospective review of patients undergoing laparoscopic segmental colectomy by one of colorectal surgeons from 2012 to 2013. Patient demographics, operative characteristics, and postoperative factors were examined. A multiple linear regression model was used to examine the impact of various factors on length of stay, while controlling for confounding variables. Systemic inflammatory response syndrome (SIRS) was defined using Society of Critical Care Medicine consensus definitions. RESULTS: A total of 127 patients underwent a laparoscopic segmental colectomy. When controlling for confounding variables, ileus, postoperative complication, and SIRS response were associated with 2.67, 1.16, and 0.42 additional hospital days, respectively, while each additional liter of urine output on postoperative day 1 was associated with a 0.23-day decrease in LOS (p = 0.006). CONCLUSIONS: In the absence of postoperative ileus or overt complication, patients who do not exhibit a SIRS response, and have a brisk urine output on postoperative day (POD) 1, may be targeted for early hospital discharge after laparoscopic colectomy.

Is sacral neuromodulation here to stay? Clinical outcomes of a new treatment for fecal incontinence.

INTRODUCTION: Sacral neuromodulation (SNM) was approved by the FDA for the treatment of fecal incontinence (FI) in 2011, and previous industry-sponsored trials have shown excellent clinical outcomes. The purpose of this study is to examine clinical outcomes of patients treated during our initial experience with SNM. METHODS: A prospective database of patients treated with SNM for FI by one of three colorectal surgeons at two separate institutions was maintained starting in 2011. Patients showing ≥50% improvement of weekly incontinent episodes during test stimulation were offered permanent implantation of the SNM device. Disease severity was tracked using the Wexner score. RESULTS: A total of 145 patients received a full system implantation (of 152 who received test stimulation). The median preoperative Wexner score of 14 decreased to 3, 3 months after implantation and persisted to 12 months. At 12 months, 95.2% of patients achieved >50% improvement in Wexner Score and 67.6% achieved >75% improvement. The most common adverse event was infection (3.4%). Three patients (2.1%) required lead revision. CONCLUSIONS: SNM is a safe and effective therapy for the treatment of FI. Postoperative patient surveillance is important, as many patients require programming changes, and some will require a lead revision over time.

Factors associated with 30-day readmission after restorative proctocolectomy with IPAA: a national study.

BACKGROUND: Hospital readmission has been identified by many payers as a surrogate for surgical quality. The 30-day readmission rate and factors associated with hospital readmission after restorative proctocolectomy with IPAA have not been well studied. OBJECTIVE: The purpose of this work was to identify the rate of and factors associated with hospital readmission within 30 days of restorative proctocolectomy with IPAA. DESIGN: A retrospective review of patients undergoing IPAA from 2009 to 2012 in the University HealthSystem Consortium database was performed. Hospitals were stratified into quartiles according to the number of cases performed annually. SETTING: This study was conducted using a national database of university hospitals. PATIENTS: A total of 4952 patients within the 4-year study period were included in the analysis. MAIN OUTCOME MEASURES: The primary outcome measured was readmission within 30 days of discharge. RESULTS: The 30-day readmission rate was 22.8% overall, although high-volume centers performed significantly better than low-volume centers (high vs low volume: 19.7% vs 28.2%; p < 0.001). When controlling for confounding variables, multivariate analysis identified female sex (OR, 1.191; p = 0.02), government-based (vs private) insurance (OR, 1.364; p < 0.001), and higher preoperative severity of illness (OR, 1.491; p = 0.001) to be associated with readmission. In addition, a significant volume-dependent relationship on 30-day readmission was identified, wherein undergoing operation at the higher-volume hospitals was protective for predicting readmission. Hierarchical regression modeling indicated that 31% of the variation in readmission rates among individual hospitals was accounted for by hospital volume. LIMITATIONS: This study was limited by its retrospective nature and limited postoperative complication data. CONCLUSIONS: The national 30-day readmission after IPAA creation was 22.8%, at least double that of other colorectal procedures. This high rate of readmission was mitigated by centers performing the highest volume of cases. Avoidance of referral to centers performing very few of these procedures annually may improve perioperative outcomes and reduce associated morbidity.

Considerations for diagnosis and management of ileostomy-related malignancy: a report of two cases.

Malignancy associated with a long-standing ileostomy is a rare occurrence reported as early as 3 years after ileostomy placement. Patients most commonly present first to their ostomy care nurse with peristomal skin changes unresponsive to conservative measures. To elucidate presentation and management, two cases of male patients with ileostomy-related with malignancy (one lymphoma and one squamous cell carcinoma) are discussed. Both patients had undergone proctocolectomy with end ileostomy decades prior. Symptoms in the lymphoma patient included complaints of skin irritation, stoma mucosa changes and friability, and a persistent rash around the ostomy; he was found to have small bowel friability and a peristomal mass arising from the terminal ileum that was resected en bloc with the ileostomy, the surrounding skin, and associated abdominal wall musculature. The patient with squamous cell carcinoma had developed a gray-tan skin lesion around his ileostomy site; he underwent exploratory laparotomy with wide local excision of the abdominal wall including ileostomy site, distal ileum, and squamous cell carcinoma, and resiting of the ileostomy to the contralateral abdominal wall. Ostomy care providers should be aware of the clinical presentation of ostomy-associated malignancy to ensure thorough evaluation and prompt referral for surgical management are provided.