Personalized total neoadjuvant therapy (pTNT) for advanced rectal cancer with tailored treatment sequencing based on clinical stage at presentation.

BACKGROUND: This study aimed to assess short-term outcomes of a personalized total neoadjuvant treatment (pTNT) protocol, with treatment sequencing based on clinical stage at presentation. METHODS: A multidisciplinary pTNT protocol was implemented across two metropolitan hospitals. This consists of two-schema based on clinical stage: patients with distant failure risk were offered induction chemotherapy before chemoradiation (nCRT), and patients with locoregional failure risk received nCRT followed by consolidation chemotherapy. Patients underwent surgical resection unless a complete clinical response (cCR) was achieved, in which case non-operative management (NOM) was offered. A prospective cohort analysis of all patients with rectal cancer who underwent pTNT with curative intent between Jan 2019 and Aug 2022 was performed. RESULTS: Of 270 patients referred with rectal cancer, 102 received pTNT with curative intent and 79 have completed their treatment thus far. Thirty-three patients (41.8%) received induction chemotherapy and 46 (58.2%) received consolidation chemotherapy per protocol. The percentage of patients with EMVI, resectable M1 disease, cT4 disease, and positive lateral lymph nodes were 54.4%, 36.7%, 27.8% and 15.2%, respectively. Overall, 32 (40.5%) patients had cCR and 4 (5.1%) pCR, and 40 (50.6%) patients had non-operative management. Grade 3 toxicity was reported in 10.1% of patients and only three patients (3.8%) experienced Grade 4 chemotherapy-related toxicity, with no treatment related mortality. CONCLUSION: Early results with a defined two-schema pTNT protocol are encouraging and suggest that tailoring sequencing to disease risk at presentation may represent the optimal balance between local and distant disease control, as well as treatment toxicity.

Cost of postoperative ileus following colorectal surgery: A cost analysis in the Australian public hospital setting.

AIM: Postoperative ileus (POI) following surgery results in significant morbidity, drastically increasing hospital costs. As there are no specific Australian data, this study aimed to measure the cost of POI after colorectal surgery in an Australian public hospital. METHODS: A cost analysis was performed, for major elective colorectal surgical cases between 2018 and 2021 at the Royal Adelaide Hospital. POI was defined as not achieving GI-2, the validated composite measure, by postoperative day 4. Demographics, length of stay and 30-day complications were recorded retrospectively. Costings in Australian dollars were collected from comprehensive hospital billing data. Univariate and multivariate analyses were performed. RESULTS: Of the 415 patients included, 34.9% (n = 145) developed POI. POI was more prevalent in males, smokers, previous intra-abdominal surgery, and converted laparoscopic surgery (p < 0.05). POI was associated with increased length of stay (8 vs. 5 days, p < 0.001) and with higher rates of complications such as pneumonia (15.2% vs. 8.1%, p = 0.027). Total cost of inpatient care was 26.4% higher after POI (AU$37,690 vs. AU$29,822, p < 0.001). POI was associated with increased staffing costs, as well as diagnostics, pharmacy, and hospital services. On multivariate analysis POI, elderly patients, stoma formation, large bowel surgery, prolonged theatre time, complications and length of stay were predictive of increased costs (p < 0.05). CONCLUSION: In Australia, POI is significantly associated with increased complications and higher costs due to prolonged hospital stay and increased healthcare resource utilisation. Efforts to reduce POI rates could diminish its morbidity and associated expenses, decreasing the burden on the healthcare system.

Systematic review and meta-analysis of long-term oncological outcomes of lateral lymph node dissection for metastatic nodes after neoadjuvant chemoradiotherapy in rectal cancer.

BACKGROUND: Standard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). In recent years, there is growing interest in performing an additional lateral lymph node dissection (LLND). The aim of this systematic review and meta-analysis was to investigate long-term oncological outcomes of nCRT followed by TME with or without LLND in patients with pre-treatment metastatic LLNs. METHODS: PubMed, Ovid MEDLINE, Embase, Cochrane Library and Clinicaltrials.gov were searched to identify comparative studies reporting long-term oncological outcomes in pre-treatment metastatic LLNs of nCRT followed by TME and LLND (LLND+) vs. nCRT followed by TME only (LLND-). Newcastle-Ottawa risk-of-bias scale was used. Outcomes of interest included local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Summary meta-analysis of aggregate outcomes was performed. RESULTS: Seven studies, including 946 patients, were analysed. One (1/7) study was of good-quality after risk-of-bias analysis. Five-year LR rates after LLND+ were reduced (range 3-15%) compared to LLND- (11-27%; RR = 0.40, 95%CI [0.25-0.62], p < 0.0001). Five-year DFS was not significantly different after LLND+ (range 61-78% vs. 46-79% for LLND-; RR = 0.72, 95%CI [0.51-1.02], p = 0.143), and neither was five-year OS (range 69-91% vs. 72-80%; RR = 0.72, 95%CI [0.45-1.14], p = 0.163). CONCLUSION: In rectal cancers with pre-treatment metastatic LLNs, nCRT followed by an additional LLND during TME reduces local recurrence risk, but does not impact disease-free or overall survival. Due to the low quality of current data, large prospective studies will be required to further determine the value of LLND.

Malignant Features in Pretreatment Metastatic Lateral Lymph Nodes in Locally Advanced Low Rectal Cancer Predict Distant Metastases.

INTRODUCTION: Pretreatment enlarged lateral lymph nodes (LLN) in patients with locally advanced low rectal cancer are predictive for local recurrences after neoadjuvant (chemo)radiotherapy (n(C)RT) followed by total mesorectal excision (TME). Not much is known of the impact on oncological outcomes when in addition malignant features are present in enlarged LLN. PATIENTS AND METHODS: A multicenter retrospective cohort study was conducted at five tertiary referral centers in the Netherlands and Australia. All patients were diagnosed with locally advanced low rectal cancer with LLN on pretreatment magnetic resonance imaging (MRI) and underwent n(C)RT followed by TME. LLN were considered enlarged with a short axis of ≥ 5 mm. Malignant features were defined as nodes with internal heterogeneity and/or border irregularity. Outcomes of interest were local recurrence-free survival (LRFS), distant metastatic-free survival (DMFS), and overall survival (OS). RESULTS: Out of 115 patients, the majority was male (75%) and the median age was 64 years (range 26-85 years). Median pretreatment LLN short axis was 7 mm (range 5-28 mm), and 60 patients (52%) had malignant features. After a median follow-up of 47 months, patients with larger LLN (7 + mm) had a worse LRFS (p = 0.01) but no difference in DMFS (p = 0.37) and OS (p = 0.54) compared with patients with smaller LLN (5-6 mm). LLN patients with malignant features had no difference in LRFS (p = 0.20) but worse DMFS (p = 0.004) and OS (p = 0.006) compared with patients without malignant features in the LLN. Cox regression analysis identified LLN short axis as an independent factor for LR. Malignant features in LLN were an independent factor for DMFS. CONCLUSION: The current study suggests that pretreatment enlarged LLN that also harbor malignant features are predictive of a worse DMFS. More studies will be required to further explore the role of malignant features in LLN.

Local recurrences in western low rectal cancer patients treated with or without lateral lymph node dissection after neoadjuvant (chemo)radiotherapy: An international multi-centre comparative study.

BACKGROUND: In the West, low rectal cancer patients with abnormal lateral lymph nodes (LLNs) are commonly treated with neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). Additionally, some perform a lateral lymph node dissection (LLND). To date, no comparative data (nCRT vs. nCRT + LLND) are available in Western patients. METHODS: An international multi-centre cohort study was conducted at six centres from the Netherlands, US and Australia. Patients with low rectal cancers from the Netherlands and Australia with abnormal LLNs (≥5 mm short-axis in the obturator, internal iliac, external iliac and/or common iliac basin) who underwent nCRT and TME (LLND-group) were compared to similarly staged patients from the US who underwent a LLND in addition to nCRT and TME (LLND + group). RESULTS: LLND + patients (n = 44) were younger with higher ASA-classifications and ypN-stages compared to LLND-patients (n = 115). LLND + patients had larger median LLNs short-axes and received more adjuvant chemotherapy (100 vs. 30%; p < 0.0001). Between groups, the local recurrence rate (LRR) was 3% for LLND + vs. 11% for LLND- (p = 0.13). Disease-free survival (DFS, p = 0.94) and overall survival (OS, p = 0.42) were similar. On multivariable analysis, LLND was an independent significant factor for local recurrences (p = 0.01). Sub-analysis of patients who underwent long-course nCRT and had adjuvant chemotherapy (LLND-n = 30, LLND + n = 44) demonstrated a lower LRR for LLND + patients (3% vs. 16% for LLND-; p = 0.04). DFS (p = 0.10) and OS (p = 0.11) were similar between groups. CONCLUSION: A LLND in addition to nCRT may improve loco-regional control in Western patients with low rectal cancer and abnormal LLNs. Larger studies in Western patients are required to evaluate its contribution.

PyRICo-Pilot: pyridostigmine to reduce the duration of postoperative ileus after colorectal surgery - a phase II study.

AIM: Postoperative ileus (POI) is a major problem after colorectal surgery. Acetylcholinesterase inhibitors such as pyridostigmine increase gastrointestinal (GI) motility through a cholinergic anti-inflammatory pathway. The purpose of this phase II pilot study is to determine the safety of oral pyridostigmine after elective colorectal surgery. METHOD: This is a Stage 2b safety study (IDEAL framework). All adult patients undergoing elective colorectal resection or formation or reversal of stoma at the Royal Adelaide Hospital between September 2020 and January 2021 were eligible. The primary outcomes were 30-day postoperative complications, reported adverse events and GI-2 - a validated composite outcome measure of recovery of GI function after surgery, defined as the interval from surgery until first passage of stool and tolerance of a solid intake for 24 h (in whole days) in the absence of vomiting. RESULTS: Fifteen patients were included in the study. The median age was 58 (range 50-82) years and seven (47%) were men. Most participants had an American Society of Anesthesiologists grade ≥2 (53%) and the median body mass index was 27 (24-35) kg/m2 . There were 13 postoperative complications [seven were Clavien-Dindo (CD) 1, five CD 2 and one CD 3]. None appeared directly related to pyridostigmine administration, and none of the patients had any overt symptoms of excessive parasympathetic activity. Median GI-2 was 2 (1-4) days. CONCLUSION: Oral pyridostigmine appears to be safe to use after elective colorectal surgery in a select group of patients. However, considering this is a pilot study with a small sample size, larger controlled studies are needed to confirm this finding and establish efficacy for prevention of POI.

Silver Diamine Fluoride Helps Prevent Emergency Visits in Children with Early Childhood Caries.

Purpose: Early childhood caries remains a worldwide disease and often requires treatment under sedation or general anesthesia, with long waitlists. Silver diamine fluoride has been shown to arrest caries lesions. The purpose of this study was to determine whether silver diamine fluoride (SDF) application reduces emergency visits by waitlisted patients with early childhood caries (ECC). Methods: Waitlisted patients aged zero to 71 months with ECC who were treated with SDF were enrolled at the University of Florida's NCEF Pediatric Dental Center; their cumulative incidence of dental emergencies were compared with children who were waitlisted during the 16 months preceding the introduction of SDF. Data from patient records on demographics, dental visits, SDF placement, and caries arrest were abstracted. Bivariate analyses and multiple logistic regression modeling were performed. Results: Participants included 97 patients treated with SDF and 216 not treated with SDF. The cumulative incidence of dental emergencies was approximately 80 percent lower in the SDF group than in the comparison group (4.1 percent versus 17.6 percent; adjusted odds ratio equals 0.18; 95 percent confidence interval equals 0.06 to 0.54); 81 percent of SDF-treated surfaces were arrested at a follow-up visit. Conclusions: Silver diamine fluoride helps reduce emergency visits for children with early childhood caries while on treatment waitlists and confirms the effectiveness of SDF for caries arrest in primary teeth.

Feasibility study of an online modifiable Enhanced Recovery After Surgery protocol with specific focus on opioid avoidance.

BACKGROUND: The high and increasing rate of opioid use is a serious issue in the Western world affecting the population's physical and mental health. In most cases, opioid dependency starts with prescriptions by medical professionals, so efforts aimed at reducing in-hospital opioid use should result in less long-term dependency. The aim of the current study was to evaluate the feasibility of implementing an opioid-scarce protocol as part of a new online modifiable Enhanced Recovery After Surgery (mERAS) programme. METHODS: A single-centre retrospective study was conducted comparing a cohort treated under the new opioid-scarce mERAS protocol (n = 96; May 2018-Nov 2018) to those treated under the original ERAS protocol (n = 84; November 2017-April 2018). The primary outcome was the quantity and duration of opioid use. RESULTS: Fewer patients used fentanyl via intravenous patient-controlled analgesia in the mERAS group (54% versus 70%; P = 0.03). The mERAS group was also less likely to use oral oxycodone (80% versus 99%; P < 0.0001) and for a shorter duration (median 3 versus 5 days; P = 0.0002). More local anaesthetic transversus abdominis plane catheters were used in the mERAS group (34% versus 6% in the control group; P < 0.0001). CONCLUSION: Opioid use can be significantly reduced after elective colorectal surgery by employing an opioid-scarce ERAS protocol. Further data is required to confirm the clinical benefits of this approach.

A global survey of surgeons' preferences and practice with regard to laxative use after elective colorectal surgery.

PURPOSE: The role of laxatives after elective colorectal surgery is unclear, resulting in heterogenous guidelines and variability in clinical practice. This study aimed to gauge surgeons' preferences and practice with regard to laxative use following elective colorectal surgery. METHODS: A short one-minute anonymous web-based questionnaire designed in English and Chinese (Mandarin) using the Research Electronic Data Capture application (REDCap) was distributed to member surgeons of every identifiable international colorectal specialist society via email communication, physical newsletters and social media channels. Frequency of laxative use after elective colorectal surgery, type of laxative used, and, if not used, the reasons for not using laxatives were collected. RESULTS: A total of 852 surgeons, representing 28 surgical societies completed the survey: 80% were colorectal surgeons and 20% were general surgeons with colorectal interest. Twenty-seven percent of the respondents routinely prescribed laxatives after colorectal surgery. There was wide variation in the type of laxatives used, with magnesium-based laxatives (42%), macrogol (Movicol, 36%) and lactulose (Duphalac, 22%) being the most common. Geographical location was correlated with choice of laxative. Those not routinely using laxatives stated the reasons as being no evidence for benefit (48%), potential of adverse events (24%), more than one reason (21%) and other (7%). The majority (93%) non-users would consider using laxatives if better evidence was available. CONCLUSION: Most surgeons do not routinely prescribe laxatives after elective colorectal surgery due to lack of evidence. Amongst those surgeons who do use them, there is wide variability in the type of laxatives used.

Lateral Lymph Node Metastases in Locally Advanced Low Rectal Cancers May Not Be Treated Effectively With Neoadjuvant (Chemo)Radiotherapy Only.

Background: In the West, pre-treatment abnormal lateral lymph nodes (LLN+) in patients with a low locally advanced rectal cancer (AJCC Stage III), are treated with neoadjuvant (chemo)radiotherapy (nCRT), without a lateral lymph node dissection (LLND). It has been suggested, however, that LLN+ patients have higher local recurrence (LR) rates than similarly staged patients with abnormal mesorectal lymph nodes only (LLN-), but no comparative data exist. Therefore, we conducted this international multi-center study in the Netherlands and Australia of Stage III rectal cancer patients with either LLN+ or LLN- to compare oncological outcomes from both groups. Materials and Methods: Patients with Stage III low rectal cancer with (LLN+ group) or without (LLN- group) abnormal lateral lymph nodes on pre-treatment MRI were included. Patients underwent nCRT followed by rectal resection surgery with curative intent between 2009 and 2016 with a minimum follow-up of 2-years. No patient had a LLND. Propensity score matching corrected differences in baseline characteristics. Results: Two hundred twenty-three patients could be included: 125 in the LLN+ group and 98 in the LLN- group. Between groups, there were significant differences in cT-stage and in the rate of adjuvant chemotherapy administered. Propensity score matching resulted in 54 patients in each group, with equal baseline characteristics. The 5-year LR rate in the LLN+ group was 11 vs. 2% in the LLN- group (P = 0.06) and disease-free survival (DFS) was 64 vs. 76%, respectively (P = 0.09). Five-year overall survival was similar between groups (73 vs. 80%, respectively; P = 0.90). Conclusions: In Western patients with Stage III low rectal cancer, there is a trend toward worse LR rate and DFS rates in LLN+ patients compared to similarly staged LLN- patients. These results suggest that LLN+ patients may currently not be treated optimally with nCRT alone, and the addition of LLND requires further consideration.

Short- and long-term outcomes of selective pelvic exenteration surgery in a low-volume specialized tertiary setting.

BACKGROUND: Most published data on pelvic exenteration comes from high-volume quaternary units, with limited data available from outside of this setting. This study reports outcomes of selective pelvic exenteration performed in a low-volume tertiary unit with multidisciplinary support. METHODS: A retrospective review of consecutive patients who underwent pelvic exenteration surgery for rectal/anal carcinoma, or gynaecological malignancy at Royal Adelaide Hospital between June 2008 and September 2018. Descriptive statistics and Kaplan-Meier analysis of 5-year disease-free and overall survival for patients treated with curative intent were performed. RESULTS: A total of 54 patients who underwent pelvic exenteration were included. Most patients presented with primary rectal adenocarcinoma, and posterior and total pelvic exenterations were the most common operations performed (>90%). Median total operating time was 323 min, median hospital stay was 15 days, and the readmission rate was 14.8%. The overall complication rate (per patient) was 70.4%, and the re-intervention rate was 20.4%. Thirteen percent of patients required intensive care unit-admission, and there was one postoperative death (1.9%). R0 resection margins were achieved in 81.5% of patients, with R1 and R2 margins in 13.0 and 5.6% of patients, respectively. Estimated 5-year disease-free survival was 38.8%, and 5-year overall survival was 65.7%. CONCLUSION: Short- and long-term outcomes of selective pelvic exenteration surgery are acceptable in a low-volume specialized tertiary setting with suitable multidisciplinary expertise. If the required expertise is not readily available, then outside referral is recommended.

The interaction between BRAF mutation and microsatellite instability (MSI) status in determining survival outcomes after adjuvant 5FU based chemotherapy in stage III colon cancer.

PURPOSE: The predictive role of biomarkers in colon cancer is still being defined. The aim of this study is to determine the interaction between BRAF mutation and microsatellite instability (MSI) status in determining survival benefit after adjuvant 5-FU based chemotherapy in stage III colon cancer. METHODS: We performed a retrospective cohort study including all curatively resected stage III colon cancer cases over a 33-year period. A clinicopathological database was collated (adjuvant chemotherapy, age, gender, obstruction, perforation, tumor location, grade, mucin, nodal stage, extramural vascular, and perineural invasion). BRAF (V600E) mutation testing was performed and MSI status established by immunohistochemistry for mismatch repair proteins and molecular testing for National Cancer Institute panel markers. Patients were categorized into four groups for comparison: MSS and BRAF-ve (termed " traditional"), MSI and BRAF-ve (termed " presumed Lynch"), MSI and BRAF+ve (termed " sporadic MSI"), and MSS and BRAF+ve (termed " other BRAF"). The primary endpoint was cancer specific survival. Interaction testing was conducted to determine whether there were different responses to chemotherapy between groups. RESULTS: A total of 686 unselected cases met inclusion criteria and had tissue available, of which 15.7% had BRAF mutation (BRAF+ve) and 13.8% had MSI. Thirty-nine percent received chemotherapy. Overall, adjuvant chemotherapy produced a cancer specific survival benefit (HR 0.66, 95% CI, 0.49-0.88, P < 0.01). On adjusted analysis, neither BRAF nor MSI status were individually predictive of survival benefit. On adjusted analysis specifically of the chemotherapy effect in each subgroup, only patients in the presumed Lynch (HR 0.260, 95% CI, 0.09-0.80, P < 0.01) and other BRAF groups (HR 0.45, 95% CI, 0.23-0.87, P < 0.01) had a significant survival benefit from chemotherapy. On interaction testing of subgroups, adjusting for all the clinicopathological parameters, only patients in the presumed Lynch group (HR 0.277, 95% CI, 0.10-0.75, P < 0.01) gained a differentially greater benefit from chemotherapy than other groups. CONCLUSIONS: In this historical cohort, MSI testing is predictive of response to adjuvant chemotherapy in stage III colon cancer, but only when results are interpreted in combination with BRAF. This supports the role of routine testing for these biomarkers.

Intraperitoneal Local Anesthetic Instillation and Postoperative Infusion Improves Functional Recovery Following Colectomy: A Randomized Controlled Trial.

BACKGROUND: Intraperitoneal local anesthetic is an analgesic technique for inclusion in the polypharmacy approach to postoperative pain management in enhanced recovery after surgery programs. Previously, augmentation of epidural analgesia with intraperitoneal local anesthetic was shown to improve functional postoperative recovery following colectomy. OBJECTIVE: This study determines whether intraperitoneal local anesthetic improves postoperative recovery in patients undergoing colectomy, in the absence of epidural analgesia, with standardized enhanced recovery after surgery perioperative care. DESIGN: This is a multisite, double-blinded, randomized, placebo-controlled trial (ClinicalTrials.gov Identifier NCT02449720). SETTINGS: This study was conducted at 3 hospital sites in South Australia. PATIENTS: Eighty-six adults undergoing colectomy were stratified by approach (35 open; 51 laparoscopic), then randomly assigned to intraperitoneal local anesthetic (n = 44) and control (n = 42) groups. INTERVENTIONS: Patients in the intraperitoneal local anesthetic group received an intraoperative intraperitoneal ropivacaine 100-mg bolus both pre- and postdissection and 20 mg/h continuous postoperative infusion for 48 hours. Patients in the control group received a normal saline equivalent. MAIN OUTCOME MEASURES: Functional postoperative recovery was assessed by using the surgical recovery scale for 45 days; postoperative pain was assessed by using a visual analog scale; and opioid consumption, use of rescue ketamine, recovery of bowel function, time to readiness for discharge, and perioperative complications were recorded. RESULTS: The intraperitoneal local anesthetic group reported improved surgical recovery scale scores at day 1 and 7, lower pain scores, required less rescue ketamine, and passed flatus earlier than the control group (p < 0.05). The improvement in surgical recovery scale at day 7 and pain scores remained when laparoscopic colectomy was considered separately. Opioid consumption and time to readiness for discharge were equivalent. LIMITATIONS: This study was powered to detect a difference in surgical recovery scale, but not the other domains of recovery, when the intraperitoneal local anesthetic group was compared with control. CONCLUSIONS: We conclude that instillation and infusion of intraperitoneal ropivacaine for patients undergoing colectomy, including by the laparoscopic approach, decreases postoperative pain and improves functional postoperative recovery. We recommend routine inclusion of intraperitoneal local anesthetic into the multimodal analgesia component of enhanced recovery after surgery programs for laparoscopic colectomy. See Video Abstract at http://links.lww.com/DCR/A698.

Clinicopathological predictors of benefit from adjuvant chemotherapy for stage C colorectal cancer: Microsatellite unstable cases benefit.

AIM: In colorectal cancer (CRC), adjuvant therapy is offered on the basis of stage and attempts to identify factors to better target treatment have not been successful. Recent work suggested that mismatch repair deficient CRCs may not benefit from 5FU adjuvant chemotherapy but studies remain conflicting. We aimed to determine if gender, tumor site, tumor pathological characteristics and microsatellite instability (MSI) predict survival benefit from adjuvant chemotherapy in stage C CRC. METHODS: Data were collated on ACPS (Australian Clinico-pathological Staging System) stage C CRC cases that underwent curative resection over a 23-year period. Pathology was reevaluated, DNA was extracted from the formalin-fixed paraffin specimen, and MSI status was established by BAT26 instability. Multivariate analysis was performed using Cox proportional hazard model and effects modification interaction testing. RESULTS: In total 814 unselected cases were included, of whom 37% received chemotherapy. Seventy-seven cases exhibited MSI. Overall, adjuvant chemotherapy produced a cancer-specific survival benefit (HR 0.52, 95% CI 0.39-0.70; P < 0.0001). On interaction testing, none of the examined parameters significantly influenced the magnitude of that survival benefit. Chemotherapy was beneficial in both the MSI (HR 0.08, 95% CI 0.02-0.27; P = < 0.0001) and the microsatellite stable cohort (HR 0.62, 95% CI 0.47-0.81; P = 0.001). CONCLUSION: These results suggest that survival benefit from 5FU adjuvant chemotherapy for stage C CRC does not vary according to gender, site of tumor, pathological characteristics or MSI status. This study suggests that it would be unwise to exclude patients from being offered adjuvant chemotherapy on the basis of MSI.

Analysis of the projected utility of dabigatran, rivaroxaban, and apixaban and their future impact on existing Hematology and Cardiology Anticoagulation Clinics at The Johns Hopkins Hospital.

The purpose of this study is to determine the percentage of patients in the Johns Hopkins Anticoagulation Clinics that are potential candidates for the new oral anticoagulants, dabigatran, rivaroxaban, and apixaban. A retrospective chart review was conducted of patients managed in the Johns Hopkins Cardiology and Hematology Anticoagulation Clinics between November 1, 2009 and October 31, 2010. Data elements collected include demographics, primary indication for anticoagulation, renal function, hepatic function, and concomitant medications. These factors were considered against product labeling guidelines and inclusion/exclusion criteria from clinical studies to derive candidacy status for each oral anticoagulant for each patient. Patients who met at least one caution or contraindication criteria were deemed "non-candidates"; potential dosage reductions of the new oral anticoagulants were not considered. Four hundred ninety-one patients participated in the study. Among participants, 63% would be dabigatran candidates, 62% rivaroxaban candidates, and 70% would be candidates for apixaban. Dabigatran use would be cautioned against in 34%, rivaroxaban in 18 %, and apixaban in 30%. Four percent had contraindications to dabigatran, whereas 21% had contraindications to rivaroxaban. More than 60% of patients in the Johns Hopkins Anticoagulation Clinics appear to be potential candidates for each of the new oral anticoagulants, assuming they are eventually approved for the same indications as warfarin. Many patients fell into the "cautioned" category, which demonstrates the complexity associated with selecting candidates for these new agents.

Development and implementation of a pharmacist-managed inpatient anticoagulation monitoring program.

PURPOSE. A stepwise approach to development and implementation of a program to standardize and increase pharmacists' involvement in anticoagulation therapy at a large academic medical center is described. SUMMARY. In response to the Joint Commission's national goal of improved patient safety in anticoagulation therapy, a work group of pharmacy administrators, educators, clinical specialists, and decentralized pharmacists at the hospital developed the structure for a comprehensive inpatient anticoagulation program (IAP); the work group also developed a list of required competencies, educational materials, assessment methods, and mechanisms for eliciting feedback from IAP pharmacists and other patient care staff. After completion of training that included structured case-review sessions, a one-on-one shadowing experience, and competency assessment, IAP pharmacists began reviewing clinical and laboratory data on patients receiving warfarin and low-molecular-weight heparins and providing recommendations to physicians, nurse practitioners, and other health care team members. Feedback from other clinicians was generally positive, with a majority of those surveyed indicating that increased pharmacist involvement in anticoagulation monitoring and dosage adjustment resulted in improved patient care; about 80% indicated that they concurred with pharmacists' recommendations at least 75% of the time. Results of a survey of IAP pharmacists indicated increased satisfaction with their daily duties but also a need for improved pharmacist-to-pharmacist communication. CONCLUSION. Case-based advanced training and implementation of an IAP in a tertiary care hospital increased pharmacists' involvement in the management of inpatients receiving anticoagulants.

Determinants of quality of life in patients following pulmonary resection for lung cancer.

BACKGROUND: The purpose of the present study was to prospectively measure quality of life (QOL) before and after pulmonary resection for non-small cell lung cancer (NSCLC) and to determine which clinical perioperative variables predicted QOL. METHODS: Thirty-seven patients undergoing a curative resection for early-stage NSCLC were administered the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire serially. This was used to calculate a Trial Outcome Index (TOI), a measure of QOL. RESULTS: Perioperative variables associated with worse postoperative TOI included the presence of preoperative dyspnea (coefficient -7.89, 95% confidence interval -12.4 to -3.31, P = .01) and exposure to adjuvant chemotherapy (-14.7, -20.0 to -9.46, P = .001). CONCLUSIONS: Preoperative dyspnea and postoperative chemotherapy are associated with worse postoperative QOL among patients with resected, early-stage NSCLC. As adjuvant and neoadjuvant therapy protocols become more prevalent for these patients, QOL issues may assume greater importance.