Larson, David W.

BACKGROUND: Clinical trials demonstrate that postresection chemotherapy conveys survival benefit to patients with stage III colon cancer. It is unclear whether this benefit can be extrapolated to the elderly, who are underenrolled in clinical trials. OBJECTIVE: The purpose of this study was to determine outcomes of selected octogenarians with stage III colon cancer with/without postresection adjuvant therapy. DESIGN: This was a retrospective cohort study (2006–2011) using unadjusted Kaplan–Meier and adjusted Cox proportional hazards analyses of overall survival. SETTING: The study was conducted with the National Cancer Database. PATIENTS: We included patients 80 to 89 years of age who were undergoing curative-intent surgery for stage III colon cancer and excluded patients who received neoadjuvant therapy, died within 6 weeks of surgery, or had high comorbidity. MAIN OUTCOME MEASURES: Overall survival was the main measure. RESULTS: A total of 8141 octogenarians were included; 3483 (42.8%) received postresection chemotherapy, and 4658 (57.2%) underwent surgery alone. Patients receiving chemotherapy were younger (82.0 vs 84.0 years; p < 0.001), healthier (73.1% vs 70.4% with no comorbidities; p = 0.009), and more likely to have N2 disease (40.4% vs 32.8%; p < 0.001). Overall survival was improved in patients receiving adjuvant chemotherapy (median = 61.7 vs 35.0 months; p < 0.001). Subgroup analysis of patients offered chemotherapy but refusing (n = 1315) demonstrated overall survival worse than those receiving adjuvant chemotherapy (median = 42.7 vs 61.7 months; p < 0.001). Multivariable analysis adjusting for potential confounders showed therapy with surgery alone to be independently associated with increased mortality hazard (HR = 1.83; p < 0.001), and the mortality hazard remained elevated in patients who voluntarily refused adjuvant therapy (HR = 1.45; p < 0.001). LIMITATIONS: The study was limited by its retrospective, nonrandomized design. CONCLUSIONS: In selected octogenarians with stage III colon cancer, postresection adjuvant chemotherapy was associated with superior overall survival. However, less than half of the octogenarians with stage III colon cancer in the National Cancer Database received it. The remaining majority, who were all fit and survived ≥6 weeks postsurgery, could have derived benefit from adjuvant chemotherapy. This represents a substantial opportunity for quality improvement in treating octogenarians with stage III colon cancer.

Patient-centered cognitive support has been shown to be critically important to facilitate the effective use of health information technologies (HIT). There is a well-documented need to better understand HIT-mediated clinical workflow. Current technologies can burden clinicians’ cognitive resources, which is associated with patient safety risks and medical errors. We sought to employ a distributed cognition approach to examine how information flows across the activity system to support clinicians’ problem-solving. Specifically, we studied the propagation of representational states across media, conversations, actors and time in the coordination of patient-care processes. We examined multiple instances of work and information flow in a real-world setting, revealing problems in information flow: a) use of paper artifacts has limitations to facilitating coordination of care, b) clinicians challenged in developing shared awareness, c) responsibility of representing patient states is distributed across documents, d) clinical reasoning that informed care plans was absent from documents. Findings surface a challenge to automated monitoring of care goals; much of the information is present only in clinicians’ minds and in informal documents.

Human jejunum smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs) express the SCN5A-encoded voltage-gated, mechanosensitive sodium channel NaV1.5. NaV1.5 contributes to small bowel excitability, and NaV1.5 inhibitor ranolazine produces constipation by an unknown mechanism. We aimed to determine the presence and molecular identity of Na+ current in the human colon smooth muscle and to examine the effects of ranolazine on Na+ current, mechanosensitivity, and smooth muscle contractility. Inward currents were recorded by whole cell voltage clamp from freshly dissociated human colon SMCs at rest and with shear stress. SCN5A mRNA and NaV1.5 protein were examined by RT-PCR and Western blots, respectively. Ascending human colon strip contractility was examined in a muscle bath preparation. SCN5A mRNA and NaV1.5 protein were identified in human colon circular muscle. Freshly dissociated human colon SMCs had Na+ currents (−1.36 ± 0.36 pA/pF), shear stress increased Na+ peaks by 17.8 ± 1.8% and accelerated the time to peak activation by 0.7 ± 0.3 ms. Ranolazine (50 μM) blocked peak Na+ current by 43.2 ± 9.3% and inhibited shear sensitivity by 25.2 ± 3.2%. In human ascending colon strips, ranolazine decreased resting tension (31%), reduced the frequency of spontaneous events (68%), and decreased the response to smooth muscle electrical field stimulation (61%). In conclusion, SCN5A-encoded NaV1.5 is found in human colonic circular smooth muscle. Ranolazine blocks both peak amplitude and mechanosensitivity of Na+ current in human colon SMCs and decreases contractility of human colon muscle strips. Our data provide a likely mechanistic explanation for constipation induced by ranolazine.

AbstractBackgroundThe aim of the study was to assess which aspects of an enhanced recovery programme are associated with better outcomes following laparoscopic colorectal surgery.MethodsA database of laparoscopic colorectal procedures performed in 2011 was reviewed. Elements of the enhanced recovery programme and compliance were evaluated for short-term (30-day) outcomes. Individual elements included gabapentin, celecoxib, intrathecal analgesia, diet, postoperative fluids, and paracetamol/non-steroidal anti-inflammatory drug pain management.ResultsFive hundred and forty-one consecutive procedures were included. Compliance with the enhanced recovery programme elements ranged from 82·4 to 99·3 per cent. Median length of hospital stay was 3 (i.q.r. 2–5) days, with 25·9 per cent of patients discharged within 48 h. Patients without complications had a median length of stay of 3 (i.q.r. 2–4) days if compliant and 3 (3–5) days if not (P &lt; 0·001). Low oral opiate intake (oral morphine equivalent of less than 30 mg) (odds ratio (OR) 1·97, 95 per cent confidence interval 1·29 to 3·03; P = 0·002), full compliance (OR 2·36, 1·42 to 3·90; P &lt; 0·001) and high surgeon volume (more than 100 cases per year) (OR 1·50, 1·19 to 1·89; P &lt; 0·001) were associated with discharge within 48 h. Compliance with the elements of oral intake and fluid management in the first 48 h was associated with a reduced rate of complications (8·1 versus 19·6 per cent; P = 0·001). Median oral opiate intake was 37·5 (i.q.r. 0–105) mg in 48 h, with 26·2 per cent of patients receiving no opiates.ConclusionCompliance with an enhanced recovery pathway was associated with less opiate use, fewer complications and a shorter hospital stay.

AbstractAimMost patients presenting with rectourethral fistula acquire it as a complication of radiotherapy for prostate cancer, as a result of injury to the rectum during prostatectomy, through trauma or from Crohn's disease. This study examined whether choice of operation and results of surgery for rectourethral fistula are influenced by prior radiotherapy.MethodMale patients undergoing surgery for rectourethral fistula were identified from a prospectively maintained database. Data regarding aetiology, surgical treatment and outcomes were analysed.ResultsFifty patients (median age = 65.5 years) were identified. Radiation was received by 29 patients for prostate or rectal cancer, and 21 patients developed a fistula following prostatectomy, Crohn's disease or pelvic fracture (without radiation). Prior to definitive surgery, 30 patients underwent fecal diversion and 37 underwent urinary diversion. In total, 57 repairs were performed (44 patients had one repair, five patients had two and one patient had three). Definitive surgery was approached predominantly abdominally in radiated patients (90.6 vs 9.3%, P < 0.001) and perineally in nonradiated patients (80 vs 20%, P < 0.001). Successful primary fistula repair was more frequent in the nonradiated group compared with the radiated group (80.9 vs 0%, P < 0.001). Permanent colostomy and urinary diversion were more often required in radiated patients than in nonradiated patients (colostomy: 83 vs 0%, P < 0.001; urorostomy: 100 vs 19%, P < 0.001).ConclusionFew patients with radiation‐induced rectourethral fistula avoid permanent colostomy and urostomy. In contrast, most patients with nonradiation‐related fistulae undergo successful perineal repair without permanent faecal and urinary diversion.

AbstractBackgroundThis study evaluated the impact of tumor regression grading (TRG) and other pathologic variates in a cohort of rectal carcinoma patients treated with neoadjuvant chemoradiotherapy (CRT). The value of a grading less than pCR for predicting survival is unknown. Tumor budding has not been systematically studied in rectal cancer after neoadjuvant therapy.MethodsPathologic risk factors for survival were evaluated on surgical specimens of 237 patients with stages I, II, and III rectal cancer treated between 1996 and 2006. All patients underwent preoperative CRT followed by surgical resection 6–8 weeks later. TRG, tumor grade, budding, venous invasion, radial margin, and nodal status were evaluated. The prognostic value of TRG categories was calculated with Cox regression models and validated with resampling methods.ResultsTRG of <25% occurred in 61 (25.7%) and a complete response in 39 (16.4%) of the resected specimens. TRG of <25% was shown to be a statistically significant predictor for cancer‐specific survival (CSS) and recurrence‐free survival (RFS) compared to TRG ≥25% (P = 0.013). Tumor budding was present in 24 (10.1%) of the patients and was negatively associated with CSS (P = 0.013). Lymph node involvement was observed in 83 (35.0%) patients. TRG and nodal status (P < 0.001) were the most significant predictors associated with outcome.ConclusionPartial pathologic response ≥25% was a superior predictor compared to pCR for improved survival after preoperative CRT. CSS and RFS were adversely affected by the presence of lymph node metastases.

Abstract Background This study determined survival and recurrence rates following curative resection of rectal cancer without radiotherapy. Methods This was a retrospective review of the Mayo Clinic database of patients with rectal cancer treated with curative intent using surgery alone from 1990 to 2006. Patients who received neoadjuvant chemotherapy or radiation therapy and those who had any postoperative radiotherapy were excluded. Details were collected from the database and patient records using a protocol approved by the institutional review board. Results Some 655 consecutive patients with rectal cancer treated with curative intent using surgery alone were identified; 397 had stage I disease, 125 stage II and 133 stage III. Four hundred and nine patients underwent anterior resection (AR) and 246 abdominoperineal resection (APR). Median follow-up was 62 months. The 5-year rate of local recurrence was 4·3 per cent, disease-free survival 90·0 per cent and cancer-specific survival 91·5 per cent. Stage-specific and all-stage disease-free survival did not differ significantly between AR and APR. The 5-year cumulative local recurrence rate was lower following AR than APR (3·6 versus 5·5 per cent; P = 0·321). There were only two patients with positive margins and type of operation was not significant on multivariable analysis. Conclusion Well-performed, standardized APRs have similar local recurrence to AR. Radiation therapy may not confer much additional benefit. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.