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.

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.

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.

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.

Safety and learning curve in robotic colorectal surgery.

Robotic surgery has recently started to be used for minimally invasive colorectal surgery. Because of limited access and high cost, very few colorectal units are available in the US. We describe our experience with benign and malignant disease since September 2008 in a dedicated colorectal practice. A prospective collected robotic database was queried for colon and rectal procedures. Anonymized demographic, intraoperative, and postoperative data, and pathology information, were collected and analyzed. A total of 48 robotic procedures for colorectal maladies were performed in the study period. There were 35 females and 13 males. The average age was 57 years. Twenty-two cases were performed for diverticulitis, 13 for malignancy (10 distal rectum (<8 cm anal verge), two rectosigmoid, and one ascending colon cancer), 10 for rectal prolapse, two for rectovaginal fistula, and one for incidental appendiceal mucocele found during a gynecologic resection. The average operating room time (OR) was 162 min and there were no conversions to open procedures. Blood loss averaged 104 mL. Mean length of hospital stay (LOS) was 5.4 days. Patient readmission occurred in 27.3% of cases. The anastamotic leak rate was 2.1% (one patient). No mortalities were reported. When the analysis was performed for colorectal malignancies (13 procedures), there were nine females and four males. Average age was 59 years. The mean OR time was 191.1 min. Mean intraoperative blood loss was 123 mL and there were no conversions to open surgery. Average LOS was 7.0 days. There was one anastamotic leak (7.7%). The length of stay was increased for the patient with anastamotic leak (18 days) and for a patient with high stoma output and postoperative ileus (17 days). Readmission rate was 30.1%. The total number of lymph nodes retrieved averaged 19.5, with a mean distal margin of 3.0 cm and in all cases negative radial margins. Robotic colorectal surgery for benign and malignant disease is safe, and short-term outcomes are comparable with those of traditional and laparoscopic surgery. Oncologic resections were adequate with excellent lymph node sampling and radial and distal margins.

The evaluation of constipation.

Constipation is a major medical problem in the United States, affecting 2% to 28% of the population. Individual patients may have different conceptions of what constipation is, and the findings overlap with those in other functional gastrointestinal disorders. In 1999, an international panel of experts laid out specific criteria for the diagnosis of constipation known as the Rome II criteria. When patients present with complaints of constipation, a complete history and physical examination can elicit the cause of constipation. It is imperative to rule out a malignancy or other organic causes of the patient's symptoms prior to making the diagnosis of functional constipation. Many patients' symptoms can be relieved with lifestyle and dietary modification, both of which should be implemented before other potentially unnecessary tests are performed. Functional constipation is divided into two subtypes: slow transit constipation and obstructive defecation. Because many different terms are used interchangeably to describe these subtypes of constipation, physicians need to be comfortable with the language. Slow transit constipation is due to abnormal colonic motility. The diagnosis is made with the use of a colonic transit study. We continue to use a single-capsule technique as first described in the literature, but modifications of the capsule technique as well as scintigraphic techniques are validated and can be substituted in place of the capsule. Obstructive defecation is a much more complex problem, with etiologies ranging from rare diseases such as Hirschsprung's to physiologic abnormalities such as paradoxical puborectalis contraction. To fully evaluate the patient with obstructive defecation, anorectal manometry, defecography, and electromyography should be utilized. The different techniques available for each test are fully covered in this article. When evaluating each patient with constipation, it is important to keep in mind that the disease may be specific to one subtype or a combination of both subtypes. Because it is difficult to differentiate the subtypes from the patient's history, we feel it is imperative to evaluate patients fully for both slow transit and obstructive defecation prior to any surgical intervention. Furthermore, we have described many tests that need to be applied to one's population of patients on the basis of the capabilities and expertise the institution offers.

Interleukin 1beta-induced production of H2O2 contributes to reduced sigmoid colonic circular smooth muscle contractility in ulcerative colitis.

We have shown that neurokinin A-induced contraction of human sigmoid circular muscle (HSCM) is reduced in patients with ulcerative colitis and that interleukin (IL)-1beta may play a role in this change. We now examine changes in the signal transduction pathway mediating neurokinin A-induced contraction of HSCM and explore the role of IL-1beta and of H(2)O(2) in these changes. In Fura 2-AM-loaded ulcerative colitis HSCM cells, neurokinin A- and caffeine-induced peak Ca(2+) increase and cell shortening were significantly reduced. In normal cells, neurokinin A-induced contraction was decreased by protein kinase C inhibitor chelerythrine and by calmodulin inhibitor CGS9343B [1,3-dihydro-1-[1-[(4-methyl-4H,6H-pyrrolo[1,2-a][4,1]-benzoxazepin-4-yl)methyl]-4-piperidinyl]-2H-benzimidazol-2-one (1:1) maleate]. In ulcerative colitis muscle cells, contraction was inhibited only by chelerythrine but not by CGS9343B. IL-1beta treatment of normal HSCM strips and cells reproduced the changes observed in ulcerative colitis. IL-1beta-induced reduction in caffeine-induced peak Ca(2+) increase and contraction was reversed by catalase, suggesting a role of H(2)O(2). IL-1beta-induced H(2)O(2) production was inhibited by mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone) and by cytosolic phospholipase A2 (cPLA(2)) inhibitor AACOCF3 (arachidonyltrifluoromethyl ketone), but neither by p38 MAPK inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole] nor by nuclear factor-kappaB (NF-kappaB) inhibitory peptide NF-kappaB SN50 (H-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Val-Gln-Arg-Lys-Arg-Gln-Lys-Leu-Met-Pro-OH). IL-1beta significantly increased the phosphorylation of extracellular signal-regulated kinase 1 (ERK1)/ERK2 MAPKs and cPLA(2) and IL-1beta-induced cPLA(2) phosphorylation was blocked by PD98059. We conclude that Ca(2+) stores of HSCM cells may be reduced in ulcerative colitis and that the signal transduction pathway of neurokinin A-induced contraction switches from calmodulin- and protein kinase C-dependent in normal cells to protein kinase C-dependent in ulcerative colitis cells. IL-1beta reproduces these changes, possibly by production of H(2)O(2) via sequential activation of MAPKs (ERK1/ERK2) and cPLA(2).

Hydrogen peroxide contributes to motor dysfunction in ulcerative colitis.

Ulcerative colitis (UC) affects colonic motor function, but the mechanism responsible for this motor dysfunction is not well understood. We have shown that neurokinin A (NKA) may be an endogenous neurotransmitter mediating contraction of human sigmoid colonic circular muscle (HSCCM). To elucidate factors responsible for UC motor dysfunction, we examined the role of hydrogen peroxide (H(2)O(2)) in the decrease of NKA-induced response of HSCCM. As previously demonstrated, NKA-induced contraction or Ca(2+) increase of normal muscle cells is mediated by release of Ca(2+) from intracellular stores, because it was not affected by incubation in Ca(2+)-free medium (CFM) containing 200 microM BAPTA. In UC, however, CFM reduced both cell contraction and NKA-induced Ca(2+) increase, suggesting reduced Ca(2+) release from intracellular stores. In normal Ca(2+) medium, NKA and KCl caused normal Ca(2+) signal in UC cells but reduced cell shortening. The decreased Ca(2+) signal and contraction in response to NKA or thapsigargin were partly recovered in the presence of H(2)O(2) scavenger catalase, suggesting involvement of H(2)O(2) in UC-induced dysmotility. H(2)O(2) levels were higher in UC than in normal HSCCM, and enzymatically isolated UC muscle cells contained much higher levels of H(2)O(2) than normal cells, which were significantly reduced by catalase. H(2)O(2) treatment of normal cells in CFM reproduced the reduction of NKA-induced Ca(2+) release observed in UC cells. In addition, H(2)O(2) caused a measurable, direct release of Ca(2+) from intracellular stores. We conclude that H(2)O(2) may contribute to reduction of NKA-induced Ca(2+) release from intracellular Ca(2+) stores in UC and contribute to the observed colonic motor dysfunction.

Abnormal motility in patients with ulcerative colitis: the role of inflammatory cytokines.

HYPOTHESIS: Interleukin 1 beta (IL-1 beta) levels are elevated in the colonic mucosa of patients with ulcerative colitis (UC). We propose that IL-1 beta may also be elevated in the circular muscle layer of the colon and may be partially responsible for the motility dysfunction observed in patients with UC. DESIGN: Cohort analytic study. SETTING: Research laboratory in a tertiary academic medical center. PARTICIPANTS: Normal smooth muscle was obtained from the disease-free margins of human sigmoid colon specimens resected from patients with cancer and compared with specimens from patients with UC. INTERVENTIONS: An enzyme-linked immunosorbent assay was used to measure IL-l beta. Standard muscle chambers were used to measure force changes. Single muscle cells were isolated by enzymatic digestion, and cell shortening in response to neurokinin A (NKA) and thapsigargin was measured under a microscope. Cytosolic Ca(2+) (calcium) concentrations were measured by standard techniques. MAIN OUTCOME MEASURE: Effects of IL-1 beta on smooth muscle function in normal and UC colons. RESULTS: In patients with UC, IL-1 beta was elevated in the muscularis propria, and sigmoid circular smooth muscle contractions in response to NKA and thapsigargin were significantly reduced. In fura-2-loaded cells from patients with UC, the NKA-induced Ca(2+) signal was also significantly reduced in Ca(2+)-free medium, indicating the reduced intracellular Ca(2+) stores after UC. Exposure of normal cells to IL-1 beta mimicked the changes observed in patients with UC. An IL-1 beta-induced reduction in contraction and release of intracellular Ca(2+) in response to NKA was partially restored by the hydrogen peroxide scavenger catalase. CONCLUSION: In patients with UC, IL-1 beta was increased in colonic circular muscles and may contribute to motor dysfunction after UC through production of hydrogen peroxide.