Integrated postoperative care model for older colorectal surgery patients improves outcomes and reduces healthcare costs.

BACKGROUND: Older surgical patients have an increased risk for postoperative complications, driving up healthcare costs. We determined if postoperative co-management of older surgery patients is associated with postoperative outcomes and hospital costs. METHODS: Retrospective data were collected for patients ≥70 years old undergoing colorectal surgery at a community teaching hospital. Patient outcomes were compared between those receiving postoperative surgery co-management care through the Optimization of Senior Care and Recovery (OSCAR) program and controls who received standard of care. Main outcome measures were postoperative complications and hospital charges, 30-day readmission rate, length of stay (LOS), and transfer to intensive care during hospitalization. Multivariable linear regression was used to model total charge and multivariable logistic regression to model complications, adjusted for multiple variables (e.g., age, sex, race, body mass index, Charlson Comorbidity Index [CCI], American Society of Anesthesiologists score, surgery duration). RESULTS: All 187 patients in the OSCAR and control groups had a similar mean CCI score of 2.7 (p = 0.95). Compared to the control group, OSCAR recipients experienced less postoperative delirium (17% vs. 8%; p = 0.05), cardiac arrhythmia (12% vs. 3%; p = 0.03), and clinical worsening requiring transfer to intensive care (20% vs. 6%; p < 0.005). OSCAR group patients had a shorter mean LOS among high-risk patients (CCI ≥3) (-1.8 days; p = 0.09) and those ≥80 years old (-2.3 days; p = 0.07) compared to the control group. Mean total hospital charge was $10,297 less per patient in the OSCAR group (p = 0.01), with $17,832 less per patient with CCI ≥3 (p = 0.01), than the control group. CONCLUSIONS: A co-management care approach after colorectal surgery in older patients improves outcomes and decreases costs, with the most benefit going to the oldest patients and those with higher comorbidity scores.

Management of the Hospitalized Patient with Acute Colitis.

Acute severe ulcerative colitis is a rapidly progressive severe form of colitis that can occur in 20-30% patients with ulcerative colitis. Early recognition, hospitalization at centers with experience and expertise and multidisciplinary treatment is the cornerstone of appropriate management of this condition. After excluding infections and other differentials, patients should be started on parenteral corticosteroids to control inflammation. ASUC patients are at high risk for thromboembolic complications and hence DVT prophylaxis is ideally started as soon as possible in the emergency room and continued throughout hospitalization. Objective criteria should be applied to assess improvement and identify patients who are unlikely to improve without second line/rescue therapy as early as 72 hours on steroid therapy. Infliximab and cyclosporine are the most used options for second line therapy and should be administered under direction by gastroenterologists. Disease progression despite aggressive treatment or non-response to second line therapy, complications such as megacolon, perforation, hemorrhage can occur requiring colectomy as a salvage option in those patients.

Can Anal Cytology Be a Tool in Following Patients Treated for Squamous Cell Carcinoma of the Anus?

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is associated with human papillomavirus infection and preceded by high-grade squamous intraepithelial lesions (HSIL). Following successful treatment, the standard of care is to surveille for local recurrence with both anoscopy and digital rectal examination. While high-resolution anoscopy (HRA) has been shown to identify HSIL during the surveillance period, it requires specialized training and resources.1 The burden of these resources may be reduced by conducting surveillance with anal cytology. We studied 2 questions: (1) Can anal cytology identify HSIL in patients after successful treatment of SCCA? (2) Can HSIL be found with anal cytology after completion of chemoradiation for SCCA? METHODS: Patient charts were queried for diagnosis of SCCA. Patients were excluded if they were not successfully treated for cure or if patients had not been seen in the surveillance period of 5 years following treatment. Descriptive statistics were elucidated. RESULTS: 104 patient charts met inclusion criteria. 81 were surveilled using standard of care, while 23 were followed with standard of care plus anal cytology. 5 patients followed with cytology demonstrated HSIL. 2/5 were found via cytology, 1/5 via HRA, and 2/5 patients via exam under anesthesia and biopsy. DISCUSSION: This study demonstrated that HSIL was identified cytologically in the surveillance period. There may be utility in using anal cytology to identify HSIL in patients during this period in lieu of the specialized resources required for HRA. This may allow dysplasia to be treated with excision and fulguration prior to redevelopment of SCCA.

Novel Approach to Removal of Rectal Foreign Bodies.

BACKGROUND: Retained rectal foreign bodies are a common concern in patients presenting to the emergency department. Thankfully, the rates of injury from these retained objects are low. Numerous techniques have been described for the extraction of these foreign bodies, including using endoscopic snares, Foley catheters to break suction mechanisms, and various kinds of clamps to grasp the objects. Some foreign bodies may not be amenable to snaring or grasping with forceps. We describe the use of laparoscopic specimen extraction bags to remove such objects. TECHNIQUE: The patient is placed in the lithotomy position under the appropriate level of anesthesia. The extraction bag is opened out of the pouch, and the metallic ring is lubricated. The ring is then compressed with 1 hand and gently guided into the rectum between the rectal wall and the foreign body with the other hand. The ring is then allowed to expand, and the foreign body is encircled. The bag is then closed around it, and the object is removed. RESULTS: The specimen-extraction bag works especially well for spherical objects and objects that are hard to grasp with clamps. We were able to extract a billiard ball and a glitter ball with this technique. It has minimal risk of injury to the rectum. CONCLUSIONS: Colorectal surgeons have a wide array of tools to use, and it is prudent to cater the tool to the task at hand. We can refashion the laparoscopic specimen extraction bag for removal of certain foreign bodies. It behooves the surgeon to consider all the tools at his or her disposal and to consider the best one for the job.

Colon and rectal surgery surgical site infection reduction bundle: To improve is to change.

BACKGROUND: Despite the introduction of the Surgical Care Improvement Project, surgical site infections remain a source of morbidity. The aim of this study was to determine the value of implementing a colorectal bundle on SSI rates. METHODS: Between 2011 and 2016 a total of 1351 patients underwent colorectal operations. Patients were grouped into pre-implementation (Group A, January 1, 2011-December 31, 2012), implementation (Group B, January 1, 2013-December 31, 2014) and post-implementation (Group C, January 1, 2015-December 31, 2016). Primary endpoints were superficial SSI, deep SSI, wound separation and total SSI. RESULTS: After the bundle was implemented, there was a significant reduction in superficial (6.6%-4%, p < 0.05), deep (3.7%-1.1%, p < 0.05), and total SSI rates (10.9%-4.7%, p < 0.05). Comparing Group A to Group C there was a decrease in total SSI (9.4%-4.7%, p < 0.05). CONCLUSION: Implementation of the bundle resulted in a reduction in overall SSI rates particularly as compliance increased. This study offers evidence that small changes can lead to significant decreases in surgical site infections.

Tolerability of ADXS11-001 Lm-LLO Listeria-Based Immunotherapy With Mitomycin, Fluorouracil, and Radiation for Anal Cancer.

PURPOSE: To obtain safety and preliminary efficacy data of the combination of ADXS11-001, live attenuated Listeria monocytogenes bacterium, with mitomycin, 5-fluorouracil (5-FU), and intensity modulated radiation therapy in locally advanced anal cancer. PATIENTS AND METHODS: Eligibility included patients with previously untreated, nonmetastatic anal cancer with a primary tumor >4 cm or node-positive disease. Patients received 2 cycles of mitomycin and 5-FU concurrent with 54.0 Gy intensity modulated radiation therapy. One intravenous dose of ADXS11-001 (1 × 109 colony-forming units) was administered before chemoradiation; 3 additional monthly doses were given after chemoradiation. RESULTS: Ten patients were treated, including 1 with N2 and 4 with N3 disease. Two patients had grade 3 acute toxicities after the initial dose of ADXS11-001, including chills/rigors (n = 2), back pain (n = 1), and hyponatremia (n = 1). All ADXS11-001 toxicities occurred within 24 hours of administration. There was no apparent increase in chemoradiation toxicities or myelosuppression. One patient had a grade 5 cardiopulmonary event shortly after beginning 5-FU treatment. All 9 assessable patients had complete clinical responses by sigmoidoscopy. Eight of 9 patients (89%) are progression-free at a median follow-up of 42 months. CONCLUSIONS: Preliminary data show that ADXS11-001 can be safely administered with standard chemoradiation for anal cancer. Further studies of listeria-based immunotherapy with radiation are warranted.

Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study.

PURPOSE: Following preoperative chemoradiation and surgery, many patients with stage II to III rectal cancer are unable to tolerate full-dose adjuvant chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic response at surgery. METHODS: Patients with clinical stage II to III (T3 to T4 and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation therapy. Surgery was performed 6 to 10 weeks after chemoradiation. RESULTS: Thirty-nine patients were enrolled between August 2010 and June 2013. Median age was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%) stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom 35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as planned. No unexpected toxicities were reported. All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in 13 patients (33%; 95% CI, 18.24%-47.76%). CONCLUSIONS: CONTRE seems to be a well-tolerated alternative to the current standard treatment sequence. Evaluating its impact on long-term outcomes would require a large randomized trial, but using pathologic response as an endpoint, it could serve as a platform for assessing the addition of novel agents to preoperative treatment in stage II to III rectal cancer.

Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation for rectal cancer.

PURPOSE: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. METHODS AND MATERIALS: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m(2)/week for 6 weeks), and continuous infusion 5-FU (200 mg/m(2)/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m(2)/week. Resection was performed 4-8 weeks after the completion of chemoradiation. RESULTS: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). CONCLUSIONS: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.

Does alvimopan enhance return of bowel function in laparoscopic right colectomy?

Alvimopan, a peripherally acting Mu-opioid receptor antagonist, has been shown to enhance recovery of gastrointestinal (GI) function in open bowel resection. The aim of this study was to determine the effect of Alvimopan on patients undergoing laparoscopic right colectomies in preventing postoperative ileus (POI). A prospective, nonrandomized trial of laparoscopic right colectomies was carried out with and without perioperative Alvimopan. The length of stay (LOS), time to first flatus, bowel movement, and tolerance of solid foods were recorded. Additionally, any occurrences of POI defined as the need for insertion of a nasogastric tube (NGT) were also noted. Student t tests were used for statistical analysis. A total of 33 patients underwent laparoscopic right colectomies for both benign and malignant diseases from October 2008, to December 2009. Sixteen patients received Alvimopan, whereas 17 patients did not. The demographics of both patient groups were similar. Patients receiving Alvimopan had an accelerated return of bowel function in terms of first flatus (2.37 vs 3.34; P = 0.03), tolerance of solid food (2.75 vs 3.94; P = 0.03), and first stool (2.53 vs 3.80; P = 0.04). There was a trend toward shorter LOS in patients receiving Alvimopan (P = 0.07). Two patients with POI requiring NGT did not receive Alvimopan. Alvimopan was successful in enhancing return of GI function in laparoscopic right colectomies and avoiding POI. The decreased LOS trended but did not approach statistical significance. A large randomized prospective trial will be needed to determine the validity of this study.

Molecular biology of squamous cell carcinoma of the anus: a comparison of HIV-positive and HIV-negative patients.

The molecular mechanisms involved in progression of squamous cell carcinoma of the anus (SCCA) are poorly elucidated, as well as the potential role of HIV infection. Loss of heterozygosity (LOH) is one of the mechanisms responsible for inactivation of tumor suppressor genes. We hypothesized that HIV-induced immunosuppression may contribute to an alternate molecular pathway in SCCA progression, through persistence of human papillomavirus infection within the anal canal. This study was undertaken to compare the molecular biology of SCCA in HIV-positive (HIV+) and HIV-negative (HIV-) patients. We retrieved tumor specimens from 18 HIV- and 10 HIV+ patients diagnosed with SCCA in two institutions. DNA from tumor and normal tissues was extracted and then amplified by polymerase chain reaction. LOH was investigated at 14 loci: three at 18q (DCC), two at 13q (Rb), three at 17p (p53), three at 11q, one at 2p, and two at 5q (APC). LOH was defined by a tumor DNA-to-normal tissue DNA ratio of >2. HIV+ patients were younger (36 +/- 7 years versus 53 +/- 13 years, P=0.001) and showed a trend toward tumors of larger size (3.7 +/- 1.6 cm versus 2.6 +/- 1.5 cm, P=0.09). The median CD4+ count in HIV+ patients at the time of diagnosis was 74 x 10(6)/L (range, 5-900). The overall frequency of LOH was 17.3% (41 LOH of 236 informative loci). Tumors in HIV- patients were more likely to present LOH than were tumors in HIV+ patients (24.1% versus 6.6%, P=0.0004). Differences between the two groups with regard to allelic losses were also observed at specific loci, such as 18q (41% [HIV-] versus 0% [HIV+], P=0.05), 17p (43% versus 10%, P=0.09), and 5q (33% versus 0%, P=0.12). Consistent LOH on chromosomes 17p, 18q, 5q, and 11q were observed in HIV- patients with SCCA. By contrast, allelic losses at 17p, 5q, and 18q seem to be rare in tumors of HIV+ individuals. These data suggest that immunosuppression may promote SCCA progression through an alternate pathway and that persistence of HPV infection within the anal canal may play a central role in this process.

A better cell cycle target for gene therapy of colorectal cancer: cyclin G.

The purpose of this study was to evaluate the overexpression of cyclin G in colorectal neoplasia, which may be a more frequent event than cyclin D1 during the cell cycle and thus may have a more enhanced therapeutic potential in treating colorectal cancer. Ninety formalin-fixed, paraffin-embedded human colon and rectal specimens were obtained from the Pathology Department of Norris Cancer Center/University of Southern California. The tissues had been obtained after surgical resection between 1995 and 2001, and had been processed by routine clinical histopathologic methods. Ninety-one percent of colorectal tumors had cyclin G overexpression. These cyclin-positive patients were evenly distributed between men and women, and between tumor locations, that is, 36% rectal tumors and 34% right-sided tumors. Thirty-two percent were well differentiated, and 66% were moderately differentiated. Thirty patients (38%) had stage I disease, 16 (20%) had stage II disease, 25 (32%) had stage III, and seven (9%) had stage IV disease. Eight patients (10%) in this group had recurrent disease during follow-up. There was no correlation between cyclin G overexpression and clinical and pathologic characteristics. Cyclin D1 overexpression was found to be present in only 42% of colorectal adenocarcinomas. There was no correlation between cyclin D1 overexpression and clinical and pathologic characteristics. The present study demonstrates that cyclin G overexpression is a frequent event in colorectal cancer. This frequent event in colorectal carcinogenesis may facilitate new therapeutic approaches acting as a target for gene therapy, possibly directed at downregulating cyclin G in colorectal cancer.